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Biomedical subjects

S Cho

Publications and source records attributed to S Cho.

At least 19 recordsLinked to original sources

Switch in glutamate receptor subunit gene expression in CA1 subfield of hippocampus following global ischemia in rats.

Severe, transient global ischemia of the brain induces delayed damage to specific neuronal populations. Sustained Ca2+ influx through glutamate receptor channels is thought to play a critical role in postischemic cell death. Although most kainate-type glutamate receptors are Ca(2+)-impermeable, Ca(2+)-permeable kainate receptors have been reported in specific kinds of neurons and glia. Recombinant receptors assembled from GluR1 and/or GluR3 subunits in exogenous expression systems are permeable to Ca2+; heteromeric channels containing GluR2 subunits are Ca(2+)-impermeable. Thus, altered expression of GluR2 in development or following a neurological insult or injury to the brain can act as a switch to modify Ca2+ permeability. To investigate the molecular mechanism underlying delayed postischemic cell death, GluR1, GluR2, and GluR3 gene expression was examined by in situ hybridization in postischemic rats. Following severe, transient forebrain ischemia GluR2 gene expression was preferentially reduced in CA1 hippocampal neurons at a time point that preceded their degeneration. The switch in expression of kainate/AMPA receptor subunits coincided with the previously reported increase in Ca2+ influx into CA1 cells. Timing of the switch indicates that it may play a causal role in postischemic cell death.

Analysis of Variance

The effects of hyperthermia on the spinal cord.

This study was conducted to obtain information about the critical temperature of the spinal cord in hyperthermia produced by radiofrequency waves applied to the spine. The first component of the spinal cord evoked potential was analyzed as an indicator of spinal cord function. The spinal cords were heated by radiofrequency waves to a maximum of 47 degrees C momentarily or for 30 minutes. The temperatures were measured with a thermosensor in the epidural space. In momentary heating, the reductions in amplitude were almost parallel with the increases in temperature. In maintained heating for 30 minutes, at 44 degrees C and below, the amplitudes decreased by one-quarter to three-quarters of the control value in the first 5 minutes and recovered to over three-quarters of the control value in 30 minutes. The amplitudes returned to almost the control value after restoration of normal spinal cord temperatures. At 45 degrees C and above, however, the amplitudes were prominently reduced or disappeared in the first 5 minutes and remained depressed during the remainder of the heating. On normalizing the temperature, the amplitudes did not return to the control value. These results suggest that 44 degrees C in the epidural space is the highest tolerable temperature for normal spinal cord function.

Animals

Purified human alpha fetoprotein inhibits growth factor-stimulated estradiol production by porcine granulosa cells in monolayer culture.

Purified alpha fetoprotein (AFP) synergizes with transforming growth factor alpha (TGF alpha) and insulin-like growth factor I (IGF-I) to enhance proliferation of porcine granulosa cells (pGC) in primary culture, suggesting a role for AFP in the modulation of growth factor-mediated cell growth. TGF alpha stimulates basal estrogen production by pGC and is in fact more potent than FSH in these cells. In this study, we investigated the effects of AFP on growth factor-stimulated estradiol (E2) production by pGC. Basal production of E2 was not altered by the addition of AFP. AFP dose-dependently inhibited TGF alpha-stimulated E2 production with statistically significant inhibition observed with 2.5 micrograms/ml. We have previously shown that the mitogenic effects of AFP are maximized with TGF alpha+IGF-I. E2 production was even more sensitive to AFP inhibition when the two growth factors were combined. Human serum albumin (HSA; 10 micrograms/ml) was without effect. AFP did not interfere with the E2 RIA, affect the uptake of or display specific in vitro binding of the androgen substrate. Furthermore, human AFP and HSA did not exhibit specific in vitro binding of E2, in contrast to purified rat AFP (positive control). These data indicate that physiological concentrations of purified AFP significantly and dose-dependently inhibit growth factor-stimulated E2 production by pGC in culture. Since AFP is known to increase TGF alpha+IGF-I mediated cell growth, these data suggest that AFP may be inhibiting the differentiated function (steroidogenesis) of pGC while enhancing the proliferation of these cells.

Amniotic Fluid

[Nutritional assessment and the effect of supplementary oral nutrition in patients with pulmonary emphysema].

Nutritional status and its relation to respiratory function and respiratory muscle strength were assessed in patients with pulmonary emphysema. Energy metabolism was also examined in order to elucidate the mechanism of their malnutrition. BCAA/AAA ratio of plasma amino acid was positively correlated with FEV1.0%. Resting energy expenditure (REE) was negatively correlated with FEV1.0%, and REE/REEpred ratio was also negatively correlated with BCAA/AAA and PImax. These findings suggest that increased mechanical work load, associated with airway obstruction and reduced respiratory muscle efficiency, contribute to the increased energy expenditure and amino acid imbalance. Oral nutritional supplementation using BCAA enriched-elemental diet was found to be effective, as assessed by nutritional parameters, PImax, D.O.E., and QOL index, in malnourished emphysema patients.

Aged

[Relation of airway obstruction and respiratory muscle weakness to energy metabolism in pulmonary emphysema].

Resting energy expenditure (REE) was assessed and its relationship to nutritional status, pulmonary function and respiratory muscle function was studied in 25 patients with pulmonary emphysema. The mean value of REE was 1413 +/- 251 Cal and the ratio of REE/REEpred was 1.398 +/- 0.23, suggesting the existence of a hypermetabolic state in these patients. REE/REEpred ratio was inversely correlated with plasma amino acid BCAA/AAA ratio and body muscle mass; and PImax. REE was inversely correlated with FEV1.0%. REE in the patient subgroup with severe hyperinflation (%RV > or = 200) was significantly higher than that in the subgroup with moderate hyperinflation. Malnourished patients showed significantly more severe hyperinflation than well-nourished patients. These findings suggest that augmented REE contributes to malnutrition in patients with emphysema, and that the increase in REE was related to the increase in mechanical work load on the basis of airway obstruction, respiratory muscle weakness and hyperinflation.

Aged

[Supplementary nutrition therapy is effective in patients with chronic obstructive pulmonary disease].

We examined the effects of supplementary nutritional therapy (calorie:REEx1.5) for one year using branched-chain amino acid (BCAA) enriched-elemental diet in addition to usual diet in 12 malnourished patients with COPD. Improvement in nutritional status was assessed by BW, %IBW, %AMC, transferrin, and plasma amino acid BCAA. PImax was significantly increased after 3 months' therapy. Although no significant change was found in pulmonary function and arterial blood gases, subjective symptoms evaluated by D.O.E., oxygen cost score and QOL index were improved. Significant correlations were found between delta BW and delta AMC and delta TSF, delta PImax and delta AMC, delta oxygen cost score and delta PImax, which suggest that improvements in nutritional status contributed to the improvement in respiratory muscle function and subjective symptoms. These findings suggest the effectiveness of supplementary nutritional therapy using BCAA-enriched elemental diet in patients with COPD.

Aged

[Evaluation of tissue eosinophils in eosinophilic pneumonia].

Transbronchial biopsy specimens from ten patients with eosinophilic pneumonia were analysed to see whether the tissue contained activated eosinophils or secreted eosinophil cationic protein. The specimens showed many infiltrated tissue eosinophils in the intraalveolar spaces, and thickened alveolar septae and perivascular areas. Most of these eosinophils stained clearly with degranulation by immunohistochemical studies with monoclonal antibody EG2 (for the secreted form of eosinophil cationic protein), indicating that they were activated eosinophils. On the other hand, although pleural tissue obtained at bullectomy performed after pneumothorax showed eosinophilic infiltration, EG2-positive cells were few. Activated eosinophils may play an important role in the development of pulmonary lesions of eosinophilic pneumonia.

Adolescent

Blockade of the AMPA receptor prevents CA1 hippocampal injury following severe but transient forebrain ischemia in adult rats.

The cytoprotective effect of NBQX, a selective AMPA receptor antagonist, was tested following 10 min of severe forebrain ischemia using the 4-vessel occlusion model. Immediately, and at 15 and 30 min following reperfusion, adult Wistar rats received intraperitoneal injections of either saline (n = 5), 1 mg lithium chloride (n = 17) or 30 mg/kg of the lithium salt of NBQX (n = 18). In saline-treated animals 82 +/- 12% of CA1 hippocampal neurons were lost. Of those treated with lithium 70 +/- 23% were injured, while those given NBQX sustained only 40 +/- 34% CA1 necrosis (P less than 0.01). Twelve of 18 NBQX-treated animals had less than 30% CA1 injury as compared with 1 of 17 lithium-treated animals. The AMPA receptor may play a more important role than the NMDA receptor in selective ischemic necrosis of hippocampal neurons.

Animals

Beneficial effects of diltiazem on the natural history of hypertensive diabetic cardiomyopathy in rats.

Hypertensive diabetic rats develop a cardiomyopathy characterized by systolic and diastolic ventricular dysfunction, myocardial hypertrophy and fibrosis, pulmonary congestion and a very high mortality rate. Alterations in contractile proteins and sarcoplasmic reticular calcium (Ca2+) transport in diabetic myocardium and their partial reversal with verapamil suggest that calcium channel blockade may prevent death from congestive heart failure in hypertensive diabetic rats. A large group of rats with renovascular hypertension and streptozotocin diabetes were divided into four groups: untreated animals (Group 1) and animals treated with 100 (Group 2), 300 (Group 3) or 600 (Group 4) mg/kg per day of sustained release diltiazem mixed in their food. Treatment was begun shortly after the onset of hypertension and diabetes. Mortality rates after 4 months were 59% (19 of 32), 53% (17 of 32), 27% (7 of 26) and 35% (12 of 34) in Groups 1, 2, 3 and 4, respectively; the mortality rate in age-matched control rats was 5% (1 of 19). The reductions in mortality rates in Groups 3 and 4 were statistically significant. Diltiazem did not change systolic blood pressure, serum glucose concentration, heart rate or left ventricular mass. There was a trend to decreased left ventricular interstitial fibrosis and perivascular fibrosis in diltiazem-treated animals. Ventricular collagen concentration was similar in untreated hypertensive diabetic and control rats; levels were higher in hypertensive diabetic rats that died than in those that survived. There was a trend to decreased collagen concentration as diltiazem dose increased. Myosin isoenzyme distribution was not changed in Groups 3 and 4 (in comparison with Group 1). In all hypertensive diabetic groups, rats that died had a higher blood pressure, heart rate, relative left ventricular mass, lung weight and lung water than did survivors. The mortality rate was two to three times higher among rats with an initial blood pressure greater than or equal to 180 mm Hg. The beneficial effects of diltiazem on survival were most significant among rats with severe hypertension.

Animals

A cluster of transcribed sequences between the Pb and Ob genes of the murine major histocompatibility complex.

The region of the murine major histocompatibility complex (MHC) between the Pb (A beta 3) and Ob (A beta 2) genes controls the expression of an intracellular complex named the LMP (low molecular weight polypeptide) complex. DNA probes for at least seven different genes mapping to this region were isolated. These hybridize to a minimum of eight different transcripts ranging from approximately 1.3 to 3.7 kilobases (kb). The deduced amino acid sequences of the corresponding cDNAs indicate that three of these genes are new members of the MHC class II gene family. These genes are transcribed in a tissue-specific pattern similar to that of the traditional class II genes. Two of the remaining four genes, HAM1 and HAM2, are homologous to one another and to a family of eukaryotic and prokaryotic transport proteins and may be involved in antigen processing. The tissue distribution of HAM1 transcripts is consistent with its proposed role in class I-restricted antigen processing, whereas HAM2 transcription appears more restricted and may be involved in antigen processing for class II-restricted T cells. The HAM2 gene may produce two differentially spliced transcripts. The identity of the remaining two genes is not known. Analyses of transcript sizes, tissue distribution, sequence, and genetic mapping data suggest that none of these genes code for LMP antigens.

Animals

Human alpha-fetoprotein purified from amniotic fluid enhances growth factor-mediated cell proliferation in vitro.

Using a primary monolayer culture of porcine granulosa cells (pGC) as an in vitro cell proliferation assay, we have examined the growth-promoting activity of alpha-fetoprotein (AFP) purified from term cord blood and midtrimester amniotic fluid. Increasing concentrations (2.5-20%) of crude human cord blood (CB) increased pGC proliferation, while identical concentrations of crude amniotic fluid (AF) were ineffective. When the cell system was maximally stimulated, AF dose dependently decreased cell proliferation. AFP purified from AF and CB (1.25-5.0 micrograms/ml) was not mitogenic alone, but, in the presence of epidermal growth factor (EGF) + insulin-like growth factor (IGF-I) (10 ng/ml each), AFP dose dependently increased cell proliferation to nearly double that of EGF + IGF-I alone. The response of pGC to the proliferative effects of AF-AFP and CB-AFP were identical at each dose of AFP tested. These results indicate that although crude, pooled midtrimester AF does not display the mitogenic activity seen in cord blood, AFP purified from pooled AF significantly synergizes with growth factors to increase cell proliferation markedly.

Amniotic Fluid

Neurological disease in xeroderma pigmentosum. Documentation of a late onset type of the juvenile onset form.

Xeroderma pigmentosum (XP) is an autosomal recessive, neurocutaneous disorder characterized by sunlight-induced skin cancers and defective DNA repair. Many XP children develop a primary neuronal degeneration. We describe 2 unusual XP patients who had a delayed onset of XP neurological disease. Somatic cell genetic studies indicated that they have the same defective DNA repair gene and are both in XP complementation group A. These 2 patients, together with a group A patient previously reported from London, establish as a distinct clinical entity the late onset type of the juvenile onset form of XP neurological disease. The functional capacity of these patients' cultured fibroblast strains to survive after treatment with ultraviolet radiation indicates that their DNA repair defect is less severe than that of typical group A patients who have a more severe neurodegeneration with an earlier symptomatic onset. The premature death of nerve cells in XP patients (which is presumably due to their inherited defects in DNA repair mechanisms) suggests that normal repair of damaged DNA in neurons is required to maintain integrity of the human nervous system.

Adolescent

A study of adult T-cell leukemia virus (ATLV) infection in the field of obstetrics: its epidemiology, vertical transmission and familial clustering.

Nine hundred and seventy-one healthy individuals in Iwate Prefecture, 659 pregnant women in Ishigaki Island, 487 pregnant women in Chiba Prefecture and 108 familial members of the ATLA-Ab-positive pregnant women (pregnant carrier women) were tested for ATLA-Ab by the PA, EIA and WB tests. 1) The rate of agreement of EIA with the PA test was 88.4% and there were no false negative sera by both examinations. These results indicate the both tests are available for mass screening. 2) In Iwate and Chiba Prefectures, the ATLA-Ab-positive rates of pregnant women were 5.3 and 0.6%, respectively. In addition, the incidences for healthy individuals ranged from 5.3 to 21.1% by age in Iwate Prefecture. Thus, Iwate Prefecture was found to equal Ishigaki Island (7.1%) in ATLA-Ab detection rates. 3) Forty-five (41.7%) out of 108 familial members of 15 pregnant carrier women were found to be seropositive for ATLA-Ab, which confirms a certain familial clustering of ATLV.

Adolescent

Synergistic action of purified alpha-fetoprotein and growth factors on the proliferation of porcine granulosa cells in monolayer culture.

alpha-Fetoprotein (AFP) is present in high levels in fetal fluids, certain neoplasias, and regenerating liver. Although AFP's physiological role remains an enigma, we have recently demonstrated mitogenic activity for AFP. Using a primary monolayer culture system, we have further investigated the proliferative activity of purified AFP. Porcine granulosa cells from small ovarian follicles were attached for 2 days in Ham's F-12-Dulbecco's Modified Eagle's Medium (1:1) and 5% fetal calf serum, followed by 6 days of culture in medium containing 0.25% plasma-derived serum plus 25 micrograms/ml low density lipoprotein with or without growth factors and/or purified human AFP. In this system AFP alone does not stimulate proliferation. However, when combined with epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I; 10 ng/ml each), AFP (5 micrograms/ml) significantly (P less than 0.01) enhanced growth factor-mediated proliferation 4.5-fold over that of medium controls. Equivalent doses of purified human serum albumin or transferrin demonstrated no effect. The effects of AFP were dose dependent, with significant (P less than 0.05) enhancement of proliferation (2.7-fold over controls) observed with as little as 0.313 micrograms/ml AFP. Increased proliferation was noticed as early as 24 h after the addition of AFP and by 48 h AFP, EGF, and IGF-I had significantly (P less than 0.05) increased proliferation over that seen in medium controls, cells treated with EGF plus IGF-I, or cells treated with 10% fetal calf serum plus EGF, and this trend continued linearly over 5 days of culture. AFP (5 micrograms/ml) significantly increased the proliferative response observed with increasing doses of EGF, IGF-I, or EGF plus IGF-I, but did not appear to alter the dose-response curves. AFP dose-dependently (1.25-5 micrograms/ml) and significantly (P less than 0.05) increased proliferation of porcine granulosa cells in response to platelet-derived growth factor (PDGF) and EGF (25 and 10 ng/ml, respectively), but not to PDGF alone. In contrast, AFP produced no further proliferation of porcine thecal cells in response to PDGF plus EGF. Binding of EGF, IGF-I, or PDGF to purified AFP could not be demonstrated. These results demonstrate that physiological levels of AFP, although not mitogenic alone, can significantly enhance the mitogenic activity of EGF plus IGF-I/PDGF and may function to modulate growth factor-mediated cell proliferation during development and neoplasia.

Animals

[Pharmacokinetic and clinical study of cefpirome in children].

Pharmacokinetic and clinical studies of cefpirome (CPR) in children were carried out, and the following results were obtained. 1. Peak serum levels were obtained at the end of drip infusion of 20.0, 17.5 and 6.8 mg/kg for 30 minutes and the half-lives were 1.93, 1.91 and 0.48 hours, respectively. 2. Urinary excretion rates in 6 hours were 40.0-96.2%. 3. Thirty-two patients including 17 with respiratory infections, 7 with urinary tract infections and 8 with skin and soft tissue infections were treated with CPR at 52.2-92 mg/kg per day by intravenous administration. Clinical effects were excellent in 12 cases, good in 13 cases, fair in 3 cases and unknown in 4 cases, and the overall efficacy rate was 89.3% (25 cases/28 cases). 4. Bacterial eradication rate was 93.8% (15 strains/16 strains). 5. Rash and diarrhea were found in 1 case each, and abnormal laboratory test values were found in 7 cases.

Adolescent

Transport protein genes in the murine MHC: possible implications for antigen processing.

T lymphocyte activation requires recognition by the T cell of peptide fragments of foreign antigen bound to a self major histocompatibility complex (MHC) molecule. Genetic evidence suggests that part of the class II region of the MHC influences the expression, in trans, of MHC class I antigens on the cell surface, by regulating the availability of peptides that bind to and stabilize the class I molecule. Two closely related genes in this region, HAM1 and HAM2, were cloned and had sequence similarities to a superfamily of genes involved in the ATP-dependent transport of a variety of substrates across cell membranes. Thus, these MHC-linked transport protein genes may be involved in transporting antigen, or peptide fragments thereof, from the cytoplasm into a membrane-bounded compartment containing newly synthesized MHC molecules.

Amino Acid Sequence

Characterization of human alpha fetoprotein charge microheterogeneity during fetal development.

Aliquotes of human amniotic fluid (AF), fetal serum (FS), and cord blood (CB) were obtained as by-products of routine clinical diagnostic procedures at term or in the second trimester of pregnancy. When samples of CB were applied to a pH 5.5-4 chromatofocusing gradient, three isoforms of AFP could be resolved; a pl 4.57 form (isoform IA, 52% AFP), a pl 4.27 form (isoform IB, 43% AFP), and one species that was bound to the column but could be eluted with 1.0 M NaCl (isoform II, pl less than 4.00, 5% AFP). Term AF displayed a profile similar to that observed in term CB. When samples of 15-20-week gestation AF were chromatofocused, the immunoreactive AFP recovered was distributed between isoform IA and IB (60%) and isoform II (40%). FS and AF obtained from same pregnancy (23-26 weeks) displayed an identical chromatofocusing profile. Aliquotes of AF subjected to conA revealed 83% reactive variants compared with greater than 95% reactive variants for CB. FS displayed a conA profile identical to CB. When individual CB charge isoforms were isolated and subjected to conA analysis, greater than 97% of the AFP bound to conA. In contrast, when AFP isoform IA and IB were isolated from midgestation AF, approximately 22% of the AFP did not bind to the lectin while 100% of isolated AFP isoform II eluted as the reactive variant. These data suggest that human AFP exists as at least three charge and two lectin variants and that the charge profile may change during fetal development.

Amniotic Fluid

Aprosencephaly: review of the literature and report of a case with cerebellar hypoplasia, pigmented epithelial cyst and Rathke's cleft cyst.

Aprosencephaly is a very rare brain malformation that occurs in isolated and sydromatic forms. The syndromatic form has been named "XK-aprosencephaly", and is characterized by near total absence of prosencephalon with a midline oculofacial defect similar to the most severe forms of holoprosencephaly, in association with limb and genital anomalies. We present a case of syndromatic aprosencephaly with absence of thumb and abnormal external genitalia. A previously undescribed finding was a Rathke's cleft cyst. Two other cystic structure were also identified--an ependymal cyst, which may represent a dorsal cyst as in holoprosencephaly, and a pigmented epithelial cyst, which may represent a rudimentary eye. Additional findings were extensive calcific vasculopathy in the rudimentary prosencephalon, absence of pituitary gland, forking of the aqueduct of Sylvius and marked cerebellar hypoplasia. Since calcific vasculopathy is a common accompaniment of other inflammatory diseases of the central nervous system, its presence in this case suggests that destructive processes may be involved in the genesis of some cases of aprosencephaly.

Abnormalities, Multiple