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Biomedical subjects

K Chin

Publications and source records attributed to K Chin.

At least 19 recordsLinked to original sources

Dynamic control of breathing during exercise and hypercapnia.

The dynamic influences of end-tidal CO2 and exercise on ventilation are compared when CO2 and exercise are imposed separately and when they are imposed simultaneously. Five human subjects are studied. The subjects performed three trials: random work rate forcing, random CO2 inhalation and their simultaneous loading. The work rate was varied between 20 and 80 W as a pseudorandom binary sequence. The concentration of inspired CO2 was varied randomly between 0 and 7 per cent, adjusted so that it produced approximately the same amount of ventilatory fluctuations as the random work load. The relative contribution of each variable was analysed using multivariate autoregressive analysis at frequencies ranging from 0.1 to 1 cycle min-1. The results show that the dynamics of the response to CO2 inhalation, exercise and their combination are nonlinear and that the combination of CO2 inhalation and exercise magnifies the nonlinear behaviour. Ventilation is largely unaffected by either work rate or end-tidal CO2 at 1 cycle min-1. During simultaneous CO2 and work rate forcing, ventilation tends to follow the change in the end-tidal CO2.

Adult

Selective effect of chronic lead ingestion on tyrosine hydroxylase activity in brain regions of rats.

Alterations of tyrosine hydroxylase activity in various regions of brain from rats postnatally exposed to lead were tested. Three groups of animals were prepared; (1) Rats exposed to lead at a low dose (0.05% lead acetate, PbAc); (2) Rats exposed to lead at a high dose (0.2% PbAc); (3) Age-matched normal control rats. At 2, 4, 6, and 8 weeks of age, weight of brain and body, and concentrations of lead in whole brain of animals in each group were measured. Activities of tyrosine hydroxylase and Na(+)-K+ ATPase were also measured at the same ages in 4 brain regions of each animal. Body weight gain was decreased after 6 weeks of age in rats exposed to lead at a high dose. Concentrations of lead in whole brain were increased from 0.37 to 0.83 (ng/mg wet tissue) in these animals. Exposure of rats to lead generally increased tyrosine hydroxylase activity and decreased Na(+)-K+ ATPase activity. However, changes of tyrosine hydroxylase activity were detected without concomitant changes of Na(+)-K+ ATPase activity in pons-medulla at 2 weeks of age and telencephalon at 6 weeks of age in rats exposed to lead at a low dose, and in midbrain at 4 and 6 weeks of age in rats exposed to lead at a high dose. These data imply that catecholaminergic nervous system in the brain regions described above could be selectively affected by lead.

Animals

[Hyperventilation syndrome].

Of 16 patients with hyperventilation syndrome (HVS), 11 experienced hypoxemic episodes (defined as PaO2 < or = 60 Torr or SaO2 < or = 90%). To investigate the relationship between hypoxemia in HVS patients and their hypoxic ventilatory response (HVR), we examined 9 of 11 HVS patients who experienced hypoxemic episodes after acute hyperventilation attacks. In order to investigate the genesis of hypoxemia after hyperventilation, we also examined minute ventilation and visual analog scale (VAS) scores representing the sensation of dyspnea at the start and at 70% arterial O2 saturation (SaO2) during HVR in 9 normal subjects under isocapnia and hypocapnia following voluntary hyperventilation (VHV). The HVR of 9 HVS patients who experienced hypoxemic episodes was normal. In 9 normal subjects, minute ventilation and VAS scores representing the sensation of dyspnea at 70% SaO2 during HVR were higher under isocapnia than under hypocapnia following VHV (p < 0.01). VAS scores taken during the HVR immediately following VHV and at 70% SaO2 were not significantly different. HVR and VAS scores representing the sensation of dyspnea were decreased under hypocapnia following VHV. These reductions were thought to be the main factors responsible for the genesis of hypoxemia following acute hyperventilation attacks in HVS patients. We conclude that hypoxemia is an important clinical sign in HVS patients, and it is important to investigate the breathing and chemical drive under hypocapnia, in order to understand the chemical regulation of breathing in HVS patients.

Adult

[Therapy and clinical symptoms in patients with obstructive sleep apnea in Japan].

To investigate the long-term outcome of therapy and clinical symptoms of patients with OSAS (obstructive sleep apnea syndrome) in Japan, we studied 34 patients with OSAS who had been diagnosed by standard polysomnography more than one years (36.0 +/- 19.7 months: mean +/- SD) previously. They were 53.8 +/- 10.5 years old, body mass index was 27.8 +/- 5.2 kg/m2, and AHI (apnea & hypopnea index) was 50.0 +/- 24.2/h. The subjects had achieved weight loss (p less than 0.01), but had regained their initial weight at our follow-up. Eleven patients with OSAS were initially candidates for NCPAP (nasal continuous positive airway pressure), but only 5 patients used it for a prolonged time. The other 6 patients with OSAS could not use NCPAP because they did not wish to purchase a NCPAP instrument. One of 5 patients who used NCPAP for a long time died from lung cancer; thus, 4 patients used NCPAP continuously. Ten patients were commenced on ACZ (acetazolamide); however, only 5 patients took it continuously. ACZ resulted in some improvements in the sleep parameters (AHI index, desaturation time below SaO2 90%), but apnea & hypopnea duration and the difference in transcutaneous PCO2 between wake and sleep were not significantly improved by ACZ administration. ACZ was not as effective as NCPAP. Almost 60% of patients with OSAS had excessive daytime sleepiness. Hypertension was detected in about 60% of patients. Nine of 25 patients who had an automobile license had had more than one automobile accident. Nine patients who had had more than one automobile accident showed AHI greater than or equal to 30 in our study.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents, Traffic

[Application of nasal intermittent positive pressure ventilation to a case of limb-girdle muscular dystrophy].

We applied nocturnal ventilation (NV) with nasal intermittent positive pressure ventilation with custom molded mask (NIPPV-C Mclermott, 1989), as well as NV with tracheostomy intermittent positive pressure ventilation (TIPPV) to a male patient with limb-girdle muscular dystrophy who had developed chronic respiratory failure at the age of 47. NV with both methods successfully corrected nocturnal hypoxemia, improved daytime arterial blood gas values, and achieved a stable clinical course without marked deterioration for four years. Daytime PaO2 higher than 60 Torr and PaCO2 lower than 70 Torr while breathing room air were maintained with both methods, whereas PaO2 was lower than 50 Torr and PaCO2 higher than 70 Torr before the implementation of NV. TIPPV was safely suspended repeatedly for as long as two weeks, maintaining daytime PaO2 higher than 50 Torr. NIPPV-C was also repeatedly suspended for two weeks. Occasionally PaO2 dropped as low as 40 Torr after periods without NV; however, it was restored to higher than 60 Torr after one or two nights' NIPPV-C. These facts suggest that NV had a restorative effect on respiratory muscle fatigue in the present case. While on NIPPV-C, nighttime SaO2 was higher than 90% for 94% of the total time, and between 80% and 90% for the remaining 6% of the time. Desaturation for short periods was thought to be due to oral air leakage, which made the method slightly less effective than TIPPV. However, the overall clinical effectiveness of NIPPV-C was comparable to that of TIPPV.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic Disease

Cloning of the human erythropoietin receptor gene.

We have isolated and characterized a genomic clone of the human erythropoietin (Epo) receptor from a placental genomic library using a cDNA probe for the murine Epo receptor. The coding region spans about 6.5 kb with seven intervening sequences ranging in size from 81 bp to 2.1 kb. A stretch of 123 purines is found in the 5' region from -456 to -578 upstream from the first codon and flanking the Alu repetitive sequences located further upstream. The human Epo receptor contains a palindromic sequence 5' of the translated region that consists of an almost perfect inverted repeat of 12 nucleotides (CAGCTGC(G/C)TCCG) centered about G at -92 from the first codon. An inverted SP1 binding site (CCGCCC) and an inverted GATA-1 binding site (TTATCT) are located at positions -151 and -179, respectively, and CACCC sequences are located at -585 and further upstream. No TATA or CAAT sequences are in this 5' flanking region. However, this region as far as -275 has a 72% GC content compared with an overall GC content of 56%. A 1-kb BamHI fragment of the human Epo receptor containing 700 bp of sequences 5' of the coding region was transcribed in an in vitro transcription assay; initiation of transcription appeared to be around 132 +/- 5 just downstream from the inverted SP1 site at -151. T1 analysis of human Epo receptor messenger RNA also maps the site of transcription initiation to this region. Within 180 nucleotides 5' to the first exon are three regions with 70% or greater homology with the murine Epo receptor. The study of this gene, including its similarities with the murine Epo receptor, should help elucidate aspects of the transcriptional and possible translational control of the Epo receptor in human erythroid cells and thus its role in signal transduction and erythroid differentiation.

Amino Acid Sequence

Tyrosine phosphorylation is an essential event in the stimulation of B lymphocytes by Staphylococcus aureus Cowan I.

Staphylococcus aureus Cowan I (SAC) is a potent mitogen for purified human B cells. By using Western blotting with antiphosphotyrosine antibodies, we demonstrated that the mitogenic effect of SAC is associated with rapid tyrosine phosphorylation of proteins of 45, 68, 75, 97, and 145 kDa. This tyrosine phosphorylation was detected within 30 s of the addition of SAC; it reached a maximum within 10 min, after which it declined gradually. In contrast to SAC, most soluble anti-IgM antibodies do not induce proliferation of isolated human B cells. As indicated by Western blotting, soluble anti-IgM antibodies induced a similar pattern of tyrosine phosphorylation, with the exception of the 68-kDa protein, which was the most heavily phosphorylated protein in SAC-treated cells. A similar but less intense 68-kDa band was also induced by mitogenic anti-IgM bound to beads. This suggested that tyrosine phosphorylation, especially of p68, may play an important role in B cell mitogenesis. To test this hypothesis, we determined the effect of specific tyrosine kinase inhibitors (tyrphostins) on SAC-induced tyrosine phosphorylation, oncogene expression, and B cell proliferation. The concentration dependencies of inhibition of these processes suggested that they were linked. Nonspecific toxic effects of the tyrphostins were ruled out by the demonstration that the tyrphostins did not alter cell viability and did not inhibit B cell proliferation induced by phorbol esters, which do not induce tyrosine phosphorylation. For maximal inhibition of SAC-induced cell proliferation, the tyrophostins needed to be added before or shortly after addition of SAC. Taken together, these data indicate that tyrosine phosphorylation is an obligatory early signal in B cell proliferation.

Antibodies, Anti-Idiotypic

Demonstration of two distinct subsets of gastric varices. Observations during a seven-year study of endoscopic sclerotherapy.

Over a seven-year period, assessment of gastric varices was made on 225 patients receiving endoscopic sclerotherapy for variceal hemorrhage. Of 170 patients with complete data, gastric varices were observed in 26 (15.3%). Importantly, two distinct subsets of gastric varices were identified: varices distal to the gastroesophageal junction without extension into the fundus, termed "junctional varices," occurred in 11.2%, and varices that were confined only to the fundus, termed "fundal varices," occurred less frequently in 4.1%. Although rebleeding was increased in both subsets of gastric varices, junctional varices were more amenable to sclerotherapy. Patients with fundal varices (N = 7) had a significantly higher rebleeding rate, increased complications with sclerotherapy, and significantly decreased survival (P less than 0.005) when compared to patients with esophageal varices alone (N = 87) who were followed for more than three months. Cumulative survival was not significantly different (P less than 0.08) in patients with junctional varices (N = 19) when compared with patients with esophageal varices alone. We conclude that not all patients with gastric varices have a poor result with sclerotherapy. Recognition of these subsets may improve treatment strategies in patients with gastric varices.

Esophageal and Gastric Varices

Natural history of dilated cardiomyopathy in children.

To assess the natural history and potential risk factors in childhood dilated cardiomyopathy, we investigated 25 patients (ages 9.6 +/- 4.4 years) who presented after they were 2 years old. All patients had symptoms of congestive heart failure and reduced contractility with a dilated left ventricle at presentation. Two factors at presentation were significantly different between patients who died less than 1 year after the presentation (n = 14) and those who survived for more than 1 year (n = 9); cardiothoracic ratio (65.1% +/- 6.8% vs 57.1% +/- 6.1%, p less than 0.01) and left ventricular ejection fraction (31.3% +/- 7.0% vs 40.0% +/- 6.2%, p less than 0.05). Irrespective of intensive medical therapy, dilated cardiomyopathy in children had a poor prognosis; the actuarial survival rate was 41% at 1 year and 20% at 3 years. Other forms of therapy should be considered in the early stages of dilated cardiomyopathy in this high-risk group.

Cardiomyopathy, Dilated

Behavioral teratogenicity of methamphetamine.

Pregnant Wistar rats were given daily subcutaneous administrations of methamphetamine (MAPT; varying doses ranging from 1.0 to 4.5 mg/kg) from days 7 to 20 of gestation and teratogenic effects have been determined. The teratogenic effects inducible with orally administered caffeine (90 mg/kg/day) for the same durations were used as the positive controls. MAPT doses greater than 2.0 mg/kg have suppressed the rate of maternal weight gain. Some of the offsprings (F1) of the prenatal MAPT treated groups had decreased growth rate and delayed development of physical characters and functional reflexes. The male offsprings of the MAPT treated groups had significant decreases in their spontaneous motor activity but had enhanced conditioned avoidance responses. However, the mating performances of these offsprings were not affected. These results indicated that prenatal exposure of MAPT may induce some behavioral teratogenicity in rats.

Animals

Regional localization of polymorphic markers on chromosome 10 by physical and genetic mapping.

The human vimentin gene and a random DNA segment (D10S39) were mapped to the short arm of human chromosome 10 by linkage analysis. A panel of somatic cell hybrids and monosomy cell-lines, which divide chromosome 10 into seven regions, was used to localize 10 polymorphic markers on this chromosome. The physical map locations obtained correlate well with linkage maps of chromosome 10. Two markers which have been shown to be closely linked to the gene for multiple endocrine neoplasia type 2A map distal to a translocation breakpoint in band 10q11.2.

Animals

[Tuberculosis sequelae: pathophysiological aspect (ventilation)].

The percentage of the patients with PaCO2 more than 60 Torr and PaO2 more than 50 Torr were 13% in the patients with tuberculosis sequela (N = 502) and 4% in the patients with chronic obstructive lung disease (COLD, N = 727), who were treated with home oxygen therapy in the western region of Japan. Patients with chronic respiratory failure caused by tuberculosis sequela have higher PaCO2 than patients with COLD. Although the prognosis of patients with hypercapnia and moderate hypoxemia is not necessarily poor, some patients may need treatment for severe hypoventilation to prevent respiratory muscle fatigue and abnormal breathing during sleep. In this study, nine patients with hypercapnic chronic respiratory failure caused by tuberculosis sequela were ventilated by Chest Negative Pressure Ventilation (CNPV). The patients were monitored as in polysomnography by transcutaneous PCO2 (PtcCO2) electrode and Respiratory Inductance Plethysmography (RIP). Tidal volume induced by CNPV was larger during mouth breathing (504 +/- 128 ml, mean +/- s.d.) than during nose breathing (438 +/- 109 ml) calculated from RIP in awake state (N = 7). Oxygen saturation measured by ear oximeter and PtcCO2 were 94.4 +/- 2.9% and 57.8 +/- 12.2 Torr in awake state. Following CNPV SaO2 and PtcCO2 were 95.7 +/- 3.0%, 42.7 +/- 12.1 Torr in awake state (N = 9) and 93.0 +/- 4.4%, 57.0 +/- 15.7 Torr in Non-REM sleep (N = 5), respectively. CNPV is effective in these patients in awake state. During Non-REM sleep, CNPV maintains the PtcCO2 level only in awake state.

Aged

[Biological properties of two newly established cell lines (RMUG-S, RMUG-L) from a human ovarian mucinous cystadenocarcinoma].

Two morphological different cell lines (RMUG-S and RMUG-L) have been established from a human ovarian mucinous cystadenocarcinoma. CA-125 and CEA were demonstrated in the patient's serum. PAS, Alcian blue and mucicarmine positive substances were observed in the original tumor and two cultured cells. The modal chromosomal numbers of RMUG-S and RMUG-L were stable in the hypodiploid and hyper-triploid ranges, respectively. Radioimmunoassay and immunocytochemical staining revealed that RMUG-S and RMUG-L mainly produced CA-125 and CEA, respectively. In CBA nude mouse, RMUG-S and RMUG-L cells mainly produced poorly-differentiated adenocarcinoma, but in mucinous cystadenocarcinoma was detected in part of the RMUG-L tumor.

Animals

[Establishment and characterization of a human chorionic gonadotropin (hCG) producing cell line (RTSG) from an ovarian epithelial cancer].

A new cell line designated RTSG established in vitro from the pleural effusion of a patient with metastatic ovarian epithelial cancer has been subcultured 46 times for more than 2 years. The cells grew in a monolayered sheet, showing a tendency to pile up, with the population doubling in 48 hrs. Electron-microscopically, desmosomes were characteristically observed, suggesting the cells were of epithelial origin. Chromosomal analysis revealed aneuploidy with a tetraploid mode. The heterotransplanted tumors in nude mice were histopathologically classified as a poorly differentiated adenocarcinoma, whereas the original tumor consisted mainly of mucinous and serous cystadenocarcinoma and only partly of poorly differentiated adenocarcinoma. The cells secreted hCG (38.8 mIU/day/10(6) cells) and beta-hCG (6.1 ng/day/10(6) cells) in spent medium. Immunocytologic +-and-histochemical staining for tumor markers of the original tumor, the cultured cells and the transplanted tumors also revealed the localization of not only hCG and beta-hCG but also CA19-9 and CA-125 whose values had been elevated in the preoperative serum (hCG: 10 mIU/ml, CA19-9: 6,400 U/ml, CA-125: 225 U/ml). Results of PAS, Alcian-blue and Mucicarmine strains indicated that most of the PAS-positive substances in the cultured cells and the transplanted tumors were consistent with glycogen while the original tumor mainly contained mucin except for the lesion of poorly differentiated adenocarcinoma with glycogen. These results suggested that the cultured cells might originate from poorly differentiated adenocarcinoma cells in the original tumor.

Adenocarcinoma

[Upper airway function and non-intubated, assisted ventilation].

The influence of upper airway patency on ventilation assisted by chest negative pressure ventilation (CNPV) or nasal intermittent positive pressure ventilation (nIPPV) was studied as follows. 1) In seven patients with chronic respiratory failure (PaCO2 more than 50 Torr), the increase in tidal volume (VT) induced by CNPV was larger during mouth breathing than during nose breathing in the awake state. On CNPV transcutaneous PCO2 (PtcCO2) decreased during awake state, but increased during NREM sleep. 2) In four patients with chronic respiratory failure (PaCO2 more than 60 Torr), nIPPV induced the leakage of air from mouth in more than 20 cmH2O of nasal mask pressure during sleep. PtcCO2 increased during sleep, especially during REM sleep in spite of nIPPV. The change in PtcCO2 during REM sleep on nIPPV comparing awake state was 16.1 +/- 1.4 torr and comparing REM sleep in usual sleep was -6.0 +/- 1.4 Torr. 3) Upper airway resistance (UAR) was measured in two patients with tracheostomy. An increase in UAR was associated with a linear decrease in VT during nIPPV, although associated with a curvilinear decrease in VT during CNPV. These results indicate that the efficiency of CNPV and nIPPV depends on the patency of upper airway.

Adult