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Using Functional Independence Measure (FIM) records, this study used latent class analysis (LCA) to clarify the structure of activities of daily living (ADL) status in patients following stroke.In this retrospective, single-center study, we extracted the medical records of patients with stroke who were admitted to a rehabilitation hospital in Japan between April 2018 and March 2020. LCA was used to determine classes of ADL status based on response patterns in FIM items converted from the original seven levels to three levels: Complete Dependence, FIM1-2; Modified Dependence, FIM3-5; Independence, FIM6-7. We compared the length of stay and discharge destinations among subgroups of patients with different ADL status at admission.From 373 patients, 1592 FIM records were analyzed. These were classified into six ADL status classes based on "Complete Dependence," "Modified Dependence," and "Independence" in the motor and cognitive domains. Significant differences were observed among the six admission ADL subgroups for the length of stay (median values in patient subgroups based on admission ADL status: 126, 146, 90, 65, 44, and 29 days in the Motor Complete/Cognitive Complete, Motor Complete/Cognitive Modified, Motor Modified/Cognitive Modified, Motor Modified/Cognitive Independent, Motor Independent/Cognitive Modified, and Motor Independent/Cognitive Independent groups, respectively) and discharge destinations (patients discharged home: 27%, 62%, 81%, 92%, 95%, and 98%, respectively, and to acute care hospitals: 18%, 14%, 8%, 8%, 2%, and 2%, respectively).LCA successfully stratified ADL status in patients with stroke undergoing rehabilitation and may aid in determining an appropriate treatment regimen.

試験におけるエラーの発生予防策を立案して実践する上では,エラーを頻回におかす学生を早期に発見して,重点的に介入する必要がある.そこで,学生の試験成績とヒューマンエラー発生との関係を明らかにした.対象は医学部6 年生102 人が受験した医師国家試験模擬試験結果である.自己採点結果と,マークシートによる機械的採点結果をもとに予期せぬ失点の原因を調べた.また,試験成績とエラー発生頻度との関係を調べた.ヒューマンエラー発生の有無によって,試験成績に有意な差はなかった.しかし,400 問あたり3 問以上のエラーをおかす受験生の得点率は61.4±6.1%であり,2 問以下のエラーをおかす受験生の得点率(65.6±5.3%)に比べて有意に低かった.成績上位者を含めた全ての受験生にエラーが生じ得るため,全学年を対象とした注意喚起が必要と思われる.また,成績下位者には多数のエラーをおかす学生が多くみられることから,これらの学生を対象とした重点的な教育介入が求められる., To examine the relationship between the occurrence ofinadvertent human errors and examination scores, the resultsof the trial examination were analyzed. The 102 of 6thgrade medical students took the trial examination for theNational Examination for Physicians' which consist of 500multiple-choice questions. More than half of the students(52.9 %) made inadvertent errors during the examination.Two-third of errors were either selecting the wrong numberof answer options( i.e. when a two choice selection wasrequired, only one choice was selected).There was no significant relationship between the occurrenceof inadvertent human errors and their scores. However,the mean score of the students who made more thantwo errors in 400 questions was 61.4±6.1%, significantlylower than those of other students( 65.6±5.3%). Attentionto avoid the inadvertent human errors during the examinationmight be emphasized for all students. Furthermore, theintervention to reduce the inadvertent human errors is especiallyneeded for the students with low scores.

試験におけるヒューマンエラーの実態を明らかにし,予防教育の効果を検証するために,医師国家試験模擬試験を利用して受験生がおかすヒューマンエラーを包括的に調査解析した.医学部6年生が2回の医師国家試験模擬試験を受験し,自己採点結果と,マークシートによる機械的採点結果を対比した.2回の試験を通じて,受験生1人が1回の試験で平均1.4個のエラーをおかしていた.エラーの分類別頻度では,2肢選択すべきところを1肢しか選択しなかったエラーが49.1%,1肢選択すべきところを2肢以上選択したエラーが31.6%,選択したものと異なる記号をマークしたエラーが10.5%と続いた.全ての受験者(全受験者)と,2回の試験に参加した受験者(2回受験者)に大別してエラーの発生頻度,エラーの内容について比較した.2 回受験者は,1人当たりがおかすエラー数および2問以上のエラーをおかす人の割合ともに2回目の試験で有意に減少していた. これは,受験者自らがエラーの実態に気付き,そして適切な助言のもとに注意を払って試験に臨んだ結果と思われる.試験におけるヒューマンエラーの実態を明らかにし,それを最小限にくい止める対策は,単に医師国家試験における失点防止だけでなく,ミスをおかしてもそれに気付き,問題解決ができるようなerror tolerantの考え方を養う上でも重要と思われる., We analyzed inadvertent human errors made by 6thgrade medical students during two trial examinations madeup of 500 multiple-choice questions where either one or twocorrect answers were required. Forty and 39 students, respectively,took the two examinations. Students averaged1.4 errors each during the examinations. Most errors( 80.7%) involved selecting the wrong number among the answeroptions( i.e. when a two option selection was required,only one option was selected). The students who had takenboth examinations made significantly less errors in the latterexamination than the former. Furthermore, the prevalenceof students who had made more than one inadvertenterror was significantly lower among students who tookboth examinations. We showed the effectiveness of interventionregarding inadvertent errors during 500 multiplechoicequestion examinations and of educating the studentsabout preventive measures. These results might have auseful application to improved safety promotions based onerror-tolerant theories.

医学部6年生を対象に,試験におけるマークミスの実態調査を行い,有用な予防対策を検討した. 36人の学生が530問の医師国家試験用模擬試験を解答し,自己採点結果と実際の採点結果を照合した.半数以上の受験生が1問以上のマークミスをおかしていた.ミスの具体的内容では,自己採点が正しいものの,マークは誤っていた場合が45.7～54.8%と最も多く,選択数を誤っていた場合が30.4%～35.7%と続いた.また, 5肢複択問題のしめる割合が増えるにしたがって,マークミスの頻度も有意に増加する傾向であった.受験者の正味試験時間を調べると,規定時間の約10%は見直し時間として利用できることがわかった.受験者は,自ら選択した解答肢が正確にマークシートに記入されているかを見直すことで,不本意な失点が防げると思われる.マークミス予防の指導は, fail-safeの対策としても重要であり,医師となった後にも十分役立つと考えられる., Multiple-choice questions (MCQs) which have been used in the National Examination for Physician's, are considered the best objective way to test examinees' acquired knowledge. In recent examinations, the MCQs consist of two types of questions, such as choosing either one correct answer or two correct answers. Although some medical students found out the correct answers of the examinations, they failed to pass the examinations due to inadvertent errors on their answer-sheets. To prevent these careless errors, we analyzed the occurrence of inadvertent errors of the trial examinations for the National Examination for Physician's, Thirty-six medical students (sixth-year) had twice taken trial examinations. Each examination consisted of 530 MCQs. The differences of the marking between self-grading and auto-grading with the scanner were investigated with each student. More than half of the students made inadvertent mistakes when marking the answer-sheets. The more examinees solve the two-correct answers questions, the more the occurrence of inadvertent errors go on increasing. Furthermore, the students spent 74.7 to 93.1% of regulated time to solve the questions. Because the students have enough time to solve the questions, they have to look at the answer-sheets again to prevent the inadvertent errors of the answers. Our results might be useful for improving points on the recent National Examination for Physician's.

第95～100回の医師国家試験問題を分析し,繰り返し出題されている重要事項を具体的かつ客観的に明らかにした.それぞれの問題を平成17年度版医師国家資格試験出題基準(ガイドライン)項目と照合し,それぞれの項目別に出題割合を計算した.また,ガイドライン別の出題回数について,過去6年間(95～100回)の医師国家試験で何回出題されていたかを調べた.必修の基本的事項では,主要疾患・外傷・症候群で,医学総論領域では,症候・検査・治療で,医師国家試験設計表の出題割合を上回って出題されていた.すなわち,臨床実習で学んだ内容についての出題が増えている傾向であった.さらに,ガイドラインであげられている事項の55.2%以上は,過去6年間に一度も出題されておらず,限られた項目の内容が頻回に出題されていた.本検討結果は,医学教育者にとって重要な点を再認識し,教育のウエイトを検討するための良い材料になったと思われる.医学教育に携わる者は,医学生が欠いてはならない最重要点を正確に把握することが重要である., The National Examination for Physician's is based on its guideline which consists of various kinds of items. To focus on frequently asked items, we analyzed the questions found in the National Examination for Physician's administered from 2001 through 2006. Each question was examined in accordance with the items of the guideline. More than half of the items in the guideline have not been asked, otherwise less than 1.4% of the items were frequently (more than 5 times) asked in the examinations administered during the past six years. Furthermore, since questions concerning clinical signs, symptoms and examinations are asked more frequently than expected, the items in which usually are learned from bed-side visits have been emphasized recently. As we clarified the important items frequently asked in the recent National Examination for Physician's, this information might be useful for medical educators to stress for the minimal essential points in the medical education.

予備校の医師国家試験模擬試験を利用して,本学学生の不得意問題抽出を行った. 2004および2005年度に行われ,全国で6,800人以上が受験した計4回の模擬試験を対象とした.各試験に出題されている全問題それぞれに対して,全国受験者および本学受験者別に平均得点率を算出した.各回とも得点率差が±10%以内に75%以上の問題が含まれた.得点率が全国平均より10%以上低い問題を不得意問題と考え,出題基準にしたがって内容を調査した.その結果,必修問題では臨床実習で学ぶべき内容が,医学総論および各論では基礎医学系の学習事項,産婦人科,小児科領域などが全受験生に比べて不得手な分野とわかった.本検討結果を教育担当者にフィードバックし,善後策を講じることで,学生に対してより平均的な実力を身につけることができるであろう., To pass the National Examination for Physician's, medical students have to gain high scores in absolute and relative evaluations of the examination. We analyzed the results of four trial examinations conducted by a preparatory school for medical students. In each question the average score of our medical students were compared to that of all medical students preparing for the examinations. We found the questions in which our students had low score with the differences of more than ten percent. According to the examination guideline, we categoried the difficult questions, and weak points of our medical students could be clarified. To gain higher scores in the relative evaluation of the examination, we have to emphasize the education for these weak categories.

We investigated the induction of metallothionein (MT) by cadmium (Cd) in the bone tissue of rats. To clarify the cell response to Cd in bone, the isoform-specific expression of MT mRNAs (MT-I and MT-II) was examined by reverse transcriptase-polymerase chain reaction (RT-PCR). Both MT-I and MT-II mRNA levels were increased within 3 h by Cd administration. MT (MT-I/MT-II) localization after single Cd injection were also confirmed by immunohistochemical studies. Notably, MT-positive cells were time-dependently increased, and the positive cells were mainly localized in osteocytes. The cell-specific induction of MT may be associated with Cd accumulation and Cd-induced bone injury in vivo. Furthermore, we also found that MT was consecutively expressed in some osteoclasts of control rats. This finding suggested a new role of osteoclasts in bone metabolism.

According to the "Guideline for Diagnosis and Treatment of Asthma" established by the Japanese Society of Allergy in 1998, inhaled adrenergic beta 2 agonists and inhaled corticosteroids are recommended for treatment of asthma. Thereafter, the development of new drugs for the treatment of asthma has begun changing. The concepts upon which the development of investigational drugs for asthma are based include improvements of drug delivery systems (ease of use, long-acting preparations, fewer side-effects), device design and appropriate auxiliary instrumentation. Moreover, chronic asthma has come to be recognized as an inflammatory disease of airway mucosa. At present, various antiallergic compounds such as tachykinin, leucotrien, PAF antagonists and others are under investigation thanks to the identification of new chemical mediators of airway inflammation and studies have progressed to the synthesis and manufacturing of new pharmaceuticals with antagonistic action. Thus, this review classified and introduced various new investigational anti-asthma and further describes the structure-activity relationships of beta 2 agonists and inhaled corticosteroids.

Metallothionein (MT)-III, originally discovered as a growth inhibitory factor (GIF), is a brain specific isomer of MTs and is markedly reduced in the brain of patients with Alzheimer's disease (AD) or other neurodegenerative diseases. We analyzed the level and regulation of mRNA expression of MT-III in immortalized fetal mouse brain glial cells (VR-2g) by reverse transcriptase-polymerase chain reaction (RT-PCR). We have recently reported that dopamine (DA) increases the expression of MT-III mRNA in vitro. In this study, we investigated the mechanism of such increase by examining the effects of DA agonists (SKF38393 or bromocriptine) and DA antagonists (SCH23390 or sulpiride) on the expression of MT-III mRNA. MT-III mRNA did not change by either agonist and DA-increased MT-III mRNA was not inhibited by either antagonist. These results suggested that the induction of MT-III mRNA by DA was not mediated by stimulation of DA receptors. On the other hand, DA-induced MT-III mRNA expression was strongly inhibited by the addition of antioxidants (glutathione, vitamin E or ascorbic acid), indicating that DA-enhanced MT-III mRNA was mediated by reactive oxygen species. Our results suggest that oxidative stress may be one of the principle factors that modulate MT-III mRNA expression.

Bisphenol A (BPA) is an endocrine disruptor, and is used as a raw material for bisphenol A diglycidyl methacrylate and polycarbonate, that are used in the dental materials. In this study, the total and released amounts of BPA from polycarbonate-based dental materials were measured with high-pressure liquid chromatography (HPLC). The specimens used were orthodontic brackets and denture base resins in the same condition as when obtained commercially were cut into 3 x 3 x 4 mm pieces and crushed into powder. The HPLC analysis was carried out after immersion of the specimens in water or ethanol for a determined time. The total amount of BPA in the specimens was analyzed after dissolution in chloroform. The amount of BPA released after immersion in water for 1 hr was 0.01-0.4 microgram/g for the block samples and 0.14-4.22 micrograms/g for the crushed samples, while that in ethanol for 1 hr was 0.12-9.42 micrograms/g for the block samples and 0.42-22.24 micrograms/g for the crushed samples. The control of BPA in the denture preform resin was 78.9 micrograms/g and this increased to 90.2 micrograms/g after heating to form dentures and then to 250 micrograms/g with mechanical crushing. The results of this study indicate that BPA is released from polycarbonates used in dentistry, and that the thermal conditions during the manufacturing of restorations may cause polymer decomposition resulting in the formation of BPA.

Complementary DNAs for angiotensin II type 1 receptor isoforms AT1A and AT1B were cloned by expression cloning from bovine adrenal and rat vascular smooth muscles. Human AT1 receptor was also cloned. Seven transmembrane structures emerged. The AT1 type receptor interacted with more than one type of G-proteins. The ligand binding site of AT1 involving Arg167, Lys199, and Asp263 has been identified by site directed mutagenesis. The regulation of the receptors occur at many stages. The isoform, AT2, was also expression cloned from rat pheochromocytoma cells. Although its ligand binding is not affected by stable GTP analogs, it is a seven transmembrane domain receptor. It mediates the modulations of phosphotyrosine phosphatase by angiotensin II and AT2 specific CGP42112A. The modulation was abolished by pertussis toxin. Thus, AT2 belongs to a new class of angiotensin receptors with unique signalling and regulatory mechanisms. AT1 mediates cellular growth. Interestingly, AT2 expression is inversely related to the mitogenic activity of cells.

The gene of human angiotensin II type 1 (AT1) receptor was isolated from a lymphocyte genomic library. The coding region of the human AT1 receptor gene was contained in a single exon coding segment of the gene indicating an intronless structure of the coding region. The amino acid sequence of human AT1 receptor deduced from its base sequence has 359 amino acids and showed a high degree of sequence identity to bovine and rat AT1 receptor sequences. Amino acid substitutions specific to the human AT1 receptor were mostly confined to the carboxy terminal half of the molecule. The seven-transmembrane domains are well-conserved in those sequences.

We have isolated the human angiotensin II (AII) type I receptor (AT 1 ) gene,whose coding region was contained within a single exon and have established Chinese hamster ovary (CHO) cell lines stably expressing this recombinant receptor. The expressed receptor revealed the typical binding characteristics of the AT 1 receptor to several AII receptor agonists and antagonists. Treatment of the intact CHO cells with the sulfhydryl reducing reagent dithiothreitol predominantly decreased the radioligand binding, indicating that a disulfhydryl bond(s) necessary for AII binding is located on extracellular domains of the receptor molecule

Cisplatin (CDDP) is a useful drug for the treatment of malignant solid tumors of the head and neck. Because CDDP includes the heavy metal platinum as a component, it is thought metallothionein (MT) may be involved in CDDP-resistance. However, functional differences between the four MT isoforms (MT-I, II, III and IV) remain unclear. The aim of this study was to investigate the relationship between MT isoform expression and CDDP-resistance. Two human tongue squamous cell carcinoma cell lines not exposed to anticancer chemotherapy were studied. The cell lines were subjected to reverse transcriptase-polymerase chain reaction (RT-PCR) analysis before and after CDDP-treatment. Both cell lines expressed MT-I/II and MT-IV isoforms but not the MT-III isoform. Following CDDP treatment, MT-I/II mRNA levels were induced only in the CDDP-resistant cell line. Our results showed that expression of the MT I/II isoform was induced by CDDP treatment, and may play an important role in CDDP-resistance in squamous cell carcinoma of the human tongue.

The purpose of this study was to evaluate the relationship between the in vivo toxicity and plasma concentration of theophylline. Theophylline was administered intravenously in single doses ( 50, 100, 150 and 200 mg kg −1 once a day) or repeated doses (12.5, 25 and 90 mg kg −1 /day for 28 days) in rats. Plasma concentrations of theophylline increased dose-dependently in both single and repeated doses, and there were no differences due to effects of 28-times repeated administration. Neither single dose at 50 mg kg −1 nor repeated dose at 12.5 mg kg −1 /day injections of theophylline showed toxic signs, in which plasma concentrations of theophylline were less than 110 and 22.5 μ g ml −1 , respectively. Theophylline induced myocardial fibrosis in 25 mg kg −1 /day and more treated groups: in which plasma concentrations of theophylline were more than 50 μ g ml −1 . At doses of 100 mg kg −1 (single) and 90 mg kg −1 /day (repeated), theophylline caused tachypnea and excitement of movement. Each theophylline concentration in plasma was more than 194 μ g ml −1 in single 100 mg kg −1 and 162 μ g ml −1 in repeated 90 mg kg −1 /day injections, respectively. Death was observed at a dose of 200 mg kg −1 , in which the plasma concentration of theophylline was more than 264 μ g ml −1 . Moreover, the recovery period from signs of toxic poisoning to normality in the 200 mg kg −1 treated group was greater than that in the 150 mg kg −1 and less treated groups. The results indicated that the in vivo toxicity of theophylline is highly dependent on plasma concentrations in rats which received single and also repeated doses of theophylline.

We investigated the induction of metallothionein (MT) by cadmium (Cd) in the dental pulp of rat incisors. Time-course studies of MT mRNA expression after single Cd injection were observed by Northern-blot analysis. The isoform-specific expressions of MT mRNAs (MT-I, MT-II and MT-III) were observed using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. Both MT-I and MT-II mRNA levels increased within 3 h, peaked at 3 h and then decreased. These findings demonstrated that MT-I and MT-II mRNA were rapidly induced by Cd in dental pulp. MT-III mRNA was constitutively expressed in rat dental pulp, but the expression level did not change by Cd treatment. The localization of MT protein in Cd-treated rat dental pulp was determined by immunohistochemical staining using anti-MT antibody against MT-I and MT-II. MT protein was localized in the specific cell type of odontoblasts (secretory odontoblasts and resting odontoblasts). In conclusion, it is likely that stained MT in the immunohistochemical study should be MT-I and/or MT-II. Furthermore, MT-I and/or MT-II in Cd-treated rat dental pulp was localized in odontoblasts, in which accumulation of Cd were reported. The cell-specific synthesis of MT may be associated with its metal storage and detoxification role in dental tissues.

Metallothioneins (MTs) have a low molecular weight and have been considered to be important metal-binding proteins in defense from cadmium (Cd) toxicity in animals. These proteins are known to be induced by the injection of heavy metals such as Cd. Previously, we developed the measurement of the MT mRNA expression by the RT-PCR method. In this study, to clarify the relation between Cd-induced MT-I mRNA expression and female sex hormones in liver, we investigated the influences of the ovariectomy and female sex hormones on hepatic MT-I mRNA expression after Cd injection, and also investigated the effects of aging on hepatic MT-I mRNA expression in mice after Cd injection. We analysed the MT-I mRNA expression by the RT-PCR method. Cd-induced MT-I mRNA expression in ovariectomized mice was more than that in sham-operated mice (9 weeks old). Both 17 β -estradiol and progesterone reduced the Cd-induced MT-I mRNA expression in ovariectomized mice (9 weeks old). Moreover, the MT-I mRNA expression in male mice was more than that of females (9 weeks old). However, the sex difference in the gene expression was not found in younger (4 weeks old) or older (46 weeks old) mice. These results suggest that the expression of hepatic MT-I mRNA after Cd injection is influenced by female sex hormones.

A biscoclaurin alkaloid preparation, cepharanthin (Ceph), is reported to have opposing pharmacological effects, enhancement or depression, on several cells and tissues, although detailed mechanisms remain unclear. Previously, we reported that Ceph enhanced lipopolysaccharide (LPS)-induced histidine decarboxylase (HDC) activity in mice spleens by consecutive pre-administration. In this study, we examined the pharmacological effects on HDC activity of a single Ceph pre-administration to test the influence of the administration method. Consequently, HDC activities were decreased by a single administration 15 minutes before LPS challenge in ddY and ICR mice spleens. Moreover, to further examine this suppressing effect, we employed genetically mast cell-deficient WBB6F1 W/Wv (W/Wv) mice to avoid the influence of mast cells. In W/Wv mice, HDC activity was enhanced, but not in the congenic WBB6F1 +/+ mice. These findings suggest that mast cells influence the depressant effect on HDC activity by a Ceph single administration in mast cell sufficient mice.

Metallothioneins (MTs) are low molecular weight proteins that have been considered to be important metal-binding proteins in the defense against cadmium (Cd) toxicity in animals. These proteins are known to be induced by the injection of heavy metals such as Cd. Previously, we developed the RT-PCR method to measure the level of MT mRNA expression. In this study, we analyzed the time course and dose response of Cd-induced MT-I mRNA expression in the male and female mouse liver. By this method, we measured hepatic MT-I mRNA expression which reached the highest peak 6 h after subcutaneous injection of 1.1 mg/kg Cd in 9-week old male and female mice compared with those of corresponding controls (0 h). There was no statistical difference in the hepatic MT-I mRNA expression between male and female mice 6 h after the injection of this dosage. However, it is notable that the MT-I mRNA expression in male mice was much higher than that in females 6 h after injection of 0.5 mg/kg Cd. Thus, the induction of hepatic MT-I mRNA expression is dependent on the sex of the mouse, the dosage and the time course of Cd.

Metallothionein (MT)-III, originally discovered as a growth inhibitory factor (GIF), is a brain specific isomer of MTs and is markedly reduced in the brain of Alzheimer's disease patients (AD) and in several other neurodegenerative diseases. We analyzed the level and regulation of mRNA expression of MT-III in immortalized fetal mouse brain glial cells (VR-2g) by reverse transcriptase-polymerase chain reaction (RT-PCR). The basal expression level of MT-III mRNA is very low in VR-2g cells. 4-Methylcatechol, dopamine (DA) and levodopa (l-3, 4-dihydroxyphenylalanine), which stimulate the synthesis of nerve growth factor (NGF), further increased the expression of MT-III mRNA in VR-2g cells.

We examined the hypothesis that hypothalamo-hypophysial tissue contains an endogenous Na pump inhibitor. From bovine posterior pituitary, we purified a substance which inhibits Rb uptake by human erythrocytes. This inhibitory activity was found in the eluate of 10% acetonitrile from a C18 flash column and purified by subsequent three steps of reversed-phase high-performance liquid chromatography (HPLC). Sequence analysis revealed that this substance was identical to joining peptide, one of the major products of proopiomelanocortin (POMC). This peptide had hypertensive and tachycardiac effects in spontaneously hypertensive rats (SHR) after central administration, with weak Na,K-ATPase inhibitory activity (IC50 = 0.5 mM).

The nucleotide and amino acid sequences for mouse angiotensin II (AII) type 1A and 1B receptors were deduced from their complementary and genomic DNAs. Evolutionary analyses based on the nucleotide sequences of the coding region of AII type 1 receptor genes indicated that the duplication event of the type 1 gene occurred 24±2 million years ago before the divergence between the rat and mouse but after the divergence between rodents and the human/artiodactyls couple. This conclusion was consistent with the results of genomic Southern blot analyses, which revealed that the mouse and rat possess 2 similar but separate genes, whereas the bovine and human have only a single class gene.

We isolated a cDNA encoding type-1 angiotensin II receptor from a human liver cDNA library. The cDNA had an open reading frame encoding a protein of 359 amino acid residues with a relative Mr of 41,060. The deduced amino acid sequence of the human angiotensin II (Ang II) receptor was 95.3% and 94.2% identical to those of bovine and rat type-1 Ang II receptors, respectively, and had a significant similarity with the G protein-coupled receptor. The rank order of the binding to the receptor expressed in COS-7 cells was Ang II greater than Ang III greater than Ang I. The expression of the Ang II receptor mRNA was detected in human liver, lung, adrenal and adrenocortical adenomas but not in adrenomedullary tumor, pheochromocytoma, by Northern blot analysis.

Metallothionein (MT) is induced in the liver not only by heavy metals, but also by stress such as starvation. However, the meaning of the induced MT during starvation has never been clear. In this study, we investigated the relationship between changes in hepatic MT synthesis and the hepatic damage that occurs during starvation. MT synthesis was assessed by measuring MT contents and the expression of the MT gene in the liver. The hepatic damage was assessed by measuring glutamic pyruvic transaminase (GPT) and glutamic oxaloacetic transaminase (GOT) activities in the serum. MT synthesis in the liver increased over the normal level by starvation, but decreased under the normal level by refeeding after starvation. Both GPT and GOT activities of the refeeding group were higher than those of the control group. However, MT synthesis increased by a subcutaneous injection with CdCl(2) (1 mg Cd /kg) at the same time as refeeding after starvation. At this point, GOT activity decreased until it reached the normal level. MT synthesis decreased by refeeding after starvation, and from the results found in this study, we proposed the hypothesis that the liver damage caused by refeeding after starvation might be due to the decrease in the synthesis of a sufficient amount of MT induced by metals.

To clarify the action of estrogenic endocrine disruptors on cadmium (Cd)-induced metallothionein (MT) synthesis in the liver, we investigated the effects of bisphenol A (BPA) on hepatic MT-I mRNA expression and MT contents after Cd injection. Liver damage after Cd injection was assessed by measuring glutamic-pyruvic transaminase (GPT) and glutamic-oxaloacetic transaminase (GOT) activities in the serum. It was found that BPA reduced the Cd-induced expression of MT-I mRNA and MT protein in the liver. The administration of tamoxifen, an estrogen receptor antagonist, prevented the reduction of hepatic MT content by PA. Moreover both the GPT and GOT activities of the BPA-treated groups were higher than those of the control groups. These findings suggest that BPA reduced hepatic MT synthesis after Cd injection via the estrogen receptor which resulted in increased damage to the liver.

Hemoglobin (Hb II) of the blood clam Anadara broughtonii has a α 2 β 2 sub-unit structure in the oxy form with a sedimentation constant of 4.8 S. When deoxygenated, Hb II polymerizes with a major component, s 20, w = 11.5 (above 150 μM in heme). Deoxy polymerization was not observed in a highly diluted protein below 20 μM (in heme). Gel filtration of Hb II in the deoxygenated state indicated that the major component has an apparent molecular weight of 195 000, which corresponds to a dodecamer. However, the sedimentation pattern and the elution profile of gel filtration showed the polymerization to be somewhat asymmetric. These results suggest that deoxy Hb II may polymerize with different polymerization states. We examined oxygen equilibria of Hb II in a range of 3–180 μM (in heme). Influences of the polymerization on its oxygen affinity and cooperativity were found to be very small. We have also found that the deoxy polymerization was completely prevented when all the sulfhydryl groups of the hemoglobin molecule were modified with p- chloromercuribenzoate .

1. 1. A copper-zinc superoxide dismutase was purified to electrophoretic homogeneity from the liver of bullfrog, Rana catesbeiana. The enzyme has a mol. wt of 32,000 and is composed of two identical subunits, each containing one copper and one zinc atom. 2. 2. The amino acid composition of the enzyme differs in the contents of glutamic acid, glycine, alanine and valine from that of the enzymes from other species. The N-terminal amino acid is methionine. The sequence of 24 residues in the N-terminal region shows a good homology with that of the human, bovine and yeast enzymes. 3. 3. As judged by a double immunodiffusion test with the antibody prepared against the frog liver enzyme, the enzymes of the frog erythrocyte and tadpole liver and erythrocyte are immunologically the same as that of the frog liver enzyme.

Thymol induced superoxide production (O 2 − ) by blood leukocytes was examined in various primates including man. Leukocytes of chimpanzee and hamadryas baboon cells showed only 35% of the maximal O 2 − production rate obtained in human cells, and those of the Japanese monkey and orang-utan failed to respond. In contrast, when cells were stimulated with 12-0-tetradecanoyl phorbol acetate, no significant difference in the O 2 − production rate was observed between human and monkey cells except for chimpanzee. These results showed that human leukocytes are the most sensitive to thymol among the primates tested. The responsiveness of non-human primate leukocytes could be classified into two types, African-type(chimpanzee and baboon) and Asian-type(orang-utan and macaque).

Peptides responsible for releasing histamine were purified from human parotid saliva. The amino acid composition of the peptides showed a high proportion of histidine, lysine and arginine. Molecular weights of these peptides were between 3000 and 5000 as determined by SDS-acrylamide gel electrophoresis. These peptides induced histamine release from rat-isolated mast cells accompanied with degranulation in a dose-dependent manner over the concentration range 5-50 micrograms/ml.

Intracellular hemoglobins of the sea blood clam Anadara broughtonii consist of HbI dimer (33%) and HbII tetramer (60%). The molecular weights of globins of HbI and HbII were determined by sodium dodecyl sulfate (SDS)-gel electrophoresis to be 15,500 and 16,500, respectively. The existence of two dissimilar chains, alpha and beta, in globin from HbII tetramer was confirmed electrophoretically and the chains were separated by CM-cellulose chromatography in 8 M urea. In contrast, globin from HbI dimer showed a single band on two types of electrophoresis. The NH2-terminus and the COOH-terminus of HbI were determined to be proline and leucine, respectively. From the results of finger-printing, the alpha and beta chains from HbII were considered to have a rather similar profile, whereas globin from HbI was very different. The results obtained by amino acid analysis of each chain also supported the above findings. It was thus shown that HbII has an alpha2beta2 subunit structure, which is rare among invertebrate hemoglobins. On the other hand, HbI seems to have two identical subunits, designated as "gamma", and to exist as a "gamma2" dimer structure. Both Anadara Hb's appear to have no functional groups relating to the Bohr effect and to be unable to form a binding site for organic phosphates.

Vibrio vulnificus protease, which had been purified from the culture supernatant of a strain isolated from a septicemic human patient, enhanced hypodermic vascular permeability and formed hemorrhagic spot caused by tissue destruction in a dose-dependent manner within a range of 0.3–10.0 μg when injected intradermally (i.d.) into rat dorsal skin. Enhancement of permeability was observed within 2 min, and the permeability-enhancing reaction terminated at 10 min after the injection. This reaction was blocked by simultaneous injection of an antihistamine, diphenhydramine, suggesting that the permeability-enhancing reaction of V. vulnificus protease was due to histamine release in vivo. Hemorrhage caused by V. vulnificus protease was also rapidly observed, but this reaction was not inhibited by the antihistamine.

1) Subcutaneous administration of CG-315 to rats was followed by rapid absorption and distribution, especially highly in lung, spleen, liver, and kidney etc. Most of the injected drug was excreted in the urine within 24 hrs and a few in the feces. 2) Part of absorbed CG-315 may be mainly metabolized in liver to either O- or N-demethylated forms, some of which are conjugated with glucuronate. 3) No difference was found in metabolism of CG-315 between non-tolerant and tolerant rats.

The 7S nerve-growth factor (7S NGF) purified from mouse submandibular glands induced histamine release from rat-isolated mast cells in the presence of lysophosphatidyl-serine. When 7S NGF was injected intradermally into the rat skin, the vascular permeability increased. This response was abolished by the antihistamine, diphenhydramine. These results show that 7S NGF acts as a potent histamine releaser.