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1.
J Med Invest ; 67(3.4): 236-239, 2020.
Article in English | MEDLINE | ID: mdl-33148894

ABSTRACT

Purpose : We investigated the cognitive function, behavioral and psychological symptoms of dementia (BPSD), and activities of daily living (ADLs) of elderly individuals admitted in care facilities. Moreover, the factors affecting the care burden experienced by facility staffs were examined. Method : 24 care facilities for elderly individuals participated in the study. The Revised Hasegawa Dementia Scale (HDS-R), Japanese version of the Neuropsychiatric Inventory (NPI), and Crichton Geriatric Behavioral Rating Scale (CGBRS) were used to evaluate cognitive function, BPSD, and ADL, respectively. The short Japanese version of the Zarit Burden Interview was used to assess the care burden. A multiple regression analysis was conducted with data obtained from 464 elderly individuals who fulfilled all the scales. Results : The care burden was correlated to the scores of HDS-R, but not with those of dysphoria/depression and disinhibition of NPI, restlessness of CGBRS, and subjective mood of CGBRS (R2 = 0.309, p < 0.005). Conclusion : Dysphoria/depression, disinhibition, restlessness, and subjective mood, but not cognitive decline, have an effect on the care burden experienced by facility staffs who manage elderly individuals. These results indicated that the appropriate diagnosis and treatment of BPSD are important in reducing the burden of facility staffs. J. Med. Invest. 67 : 236-239, August, 2020.


Subject(s)
Dementia/psychology , Activities of Daily Living , Aged , Aged, 80 and over , Cognition , Dementia/therapy , Female , Humans , Male
2.
J Med Invest ; 67(1.2): 75-82, 2020.
Article in English | MEDLINE | ID: mdl-32378622

ABSTRACT

Objective : The purpose of the present study is to examine clinical factors related to life skills in people with schizophrenia. Method : The participants were 51 stabilized outpatients with schizophrenia. Their mean age was 38.91 (SD = 10.73) years. Life skills were assessed using the Life skills profile (LSP). Cognitive function was evaluated with the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB). Clinical symptoms were assessed using the Positive and Negative Syndrome scale (PANSS), the Calgary Depression Scale for Schizophrenia (CDSS) and the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). Results : Cognitive function was not correlated with the LSP scores at all. Among clinical symptoms, scores of the PANSS positive and negative syndrome scales, the CDSS, and the DIEPSS had negative correlations with the LSP total score and the subscales. Stepwise regression analyses showed that the CDSS and PANSS negative syndrome scale scores were independent predictors of the LSP total score and two of the subscales. Conclusions : These results indicate that cognitive function is not associated with life skills but clinical symptoms such as depressive and negative symptoms have considerable impacts on life skills in people with schizophrenia. J. Med. Invest. 67 : 75-82, February, 2020.


Subject(s)
Activities of Daily Living , Cognition , Schizophrenic Psychology , Adult , Female , Humans , Male , Middle Aged
3.
Neuropsychiatr Dis Treat ; 15: 391-395, 2019.
Article in English | MEDLINE | ID: mdl-30787613

ABSTRACT

PURPOSE: This study was to elucidate clinical factors influencing resilience in anorexia nervosa (AN) patients. PATIENTS AND METHODS: Twenty female patients with AN (median age =30.0 years, quartile deviation =6.8) and 40 female healthy controls (HCs) (median age =30.0 years, quartile deviation =8.6) participated in the present study. Resilience was assessed with the Connor- Davidson resilience scale (CD-RISC). Clinical symptoms were evaluated with the structured interview guide for the Hamilton depression rating scale (SIGH-D) and the eating disorder inventory-2 (EDI-2). RESULTS: Scores of the CD-RISC in the AN group were lower than those in the HC group, and the SIGH-D score in the AN group was higher than that in the HC group. Scores of interoceptive confusion, interpersonal difficulty and negative self-image subscales of the EDI-2 negatively correlated with the CD-RISC score. Moreover, stepwise regression analysis showed that negative self-image score was an independent predictor of the CD-RISC score. CONCLUSION: These results suggest that among these clinical factors including psychopathologies, self-dissatisfaction and feeling of being rejected by others are the most important influencing factors on an AN patients' resilience.

4.
Neuropsychiatr Dis Treat ; 15: 293-301, 2019.
Article in English | MEDLINE | ID: mdl-30718955

ABSTRACT

PURPOSE: Recently, cognitive variables such as negative and positive self-belief and thoughts have attracted much attention because they are associated with functional outcomes and quality of life (QOL). However, it is unclear how cognitive variables affect subjective and objective QOL. This study aimed to investigate the relationship of negative and positive self-belief and thoughts with subjective and objective QOL. PARTICIPANTS AND METHODS: Thirty-six people with schizophrenia participated in this study. Subjective and objective QOL were assessed with the Schizophrenia Quality of Life Scale (SQLS) and Quality of Life Scale (QLS), respectively. Neurocognitive function was assessed with the Brief Assessment of Cognition in Schizophrenia (BACS). Clinical symptoms were assessed with the Positive and Negative Syndrome Scale and Calgary Depression Scale for Schizophrenia. Side effects were assessed with the Drug-induced Extrapyramidal Symptoms Scale (DIEPSS). Negative and positive self-belief and thoughts were assessed with the Defeatist Performance Belief Scale and Automatic Thoughts Questionnaire-Revised. A generalized linear model was tested, with subjective and objective QOL as the response variable and symptoms, neurocognitive function, and cognitive variables that were significantly correlated with subjective and objective QOL as explanatory variables. RESULTS: In the schizophrenia group, the common objects score on the QLS was predicted by the composite BACS score, and the total QLS score was predicted by the DIEPSS score. Motivation and Energy, Psychosocial, and Symptoms and Side effects scores on the SQLS were predicted by depression and by negative automatic thought (NAT) and positive automatic thought (PAT). CONCLUSION: Our results indicated that key targets for improving objective and subjective QOL in people with schizophrenia are side effects, neurocognitive function, depression, and NAT and PAT.

5.
Neuropsychiatr Dis Treat ; 14: 2215-2224, 2018.
Article in English | MEDLINE | ID: mdl-30214211

ABSTRACT

PURPOSE: The purpose of the present study was to examine clinical factors related to social function in people with schizophrenia. PATIENTS AND METHODS: The participants were 55 stabilized outpatients with schizophrenia. Their mean age was 39.36 (SD =10.65) years. Social function was assessed using the Quality of Life Scale (QLS). Cognitive function was evaluated with the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB). Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), the Calgary Depression Scale for Schizophrenia, and the Drug-Induced Extrapyramidal Symptoms Scale. RESULTS: Neither the MCCB cognitive domain score nor composite score was correlated with the QLS scores. However, of the 10 MCCB subtests, the Trail Making Test Part A and the Brief Assessment of Cognition in Schizophrenia-Symbol Coding (BACS-SC) scores were positively correlated with the QLS scores. Among clinical variables, especially the PANSS negative syndrome scale score had a strong negative correlation with the QLS scores. Stepwise regression analyses showed that the PANSS negative syndrome scale score was an independent predictor of the QLS scores, and although the BACS-SC score predicted the QLS common objects and activities subscale score, the association was not so strong compared to the PANSS negative syndrome scale score. CONCLUSION: These results indicate that speed of processing evaluated by BACS-SC could predict some aspect of social function but negative symptoms have a much stronger impact on global social function in people with schizophrenia.

6.
Neuropsychiatr Dis Treat ; 14: 1585-1597, 2018.
Article in English | MEDLINE | ID: mdl-29942132

ABSTRACT

PURPOSE: Quality of life (QOL) is an important clinical outcome for patients with schizophrenia, and recent studies have focused on subjective QOL. We evaluated the causal relationship between psychosocial aspect of subjective QOL, symptoms, cognitive functions, and salience network (SN) dysfunction in schizophrenia using structural equation modeling (SEM). PATIENTS AND METHODS: We performed a cross-sectional study of 21 patients with symptomatically stabilized schizophrenia and 21 age-, sex-, and education level-matched healthy controls who underwent resting-state functional magnetic resonance imaging. We evaluated SN dysfunction in schizophrenia using independent component analysis (ICA). We rated participant psychopathology using the Positive and Negative Syndrome Scale (PANSS), the Brief Assessment of Cognition in Schizophrenia (BACS), and the Calgary Depression Scale for Schizophrenia (CDSS). We rated psychosocial aspect of subjective QOL using the Schizophrenia Quality of Life Scale (SQLS) psychosocial subscale. We applied SEM to examine the relationships between SN dysfunction, PANSS positive and negative scores, CDSS total scores, BACS composite scores, and SQLS psychosocial subscale scores. RESULTS: In second-level analysis after group ICA, patient group had significant lower right pallidum functional connectivity (FC) within the SN than the controls did (Montreal Neurological Institute [MNI] [x y z] = [22 -2 -6]) (p = 0.027, family-wise error [FWE] corrected). In SEM, we obtained a good fit for an SEM model in which SN dysfunction causes depressed mood, which in turn determines psychosocial aspect of subjective QOL (chi-squared p = 0.9, root mean square error of approximation (RMSEA) < 0.001, comparative fit index [CFI] = 1.00, and standardized root mean square residual [SRMR]= 0.020). CONCLUSION: We found a continuous process by which SN dysfunction causes depressed moods that determine psychosocial aspect of subjective QOL in schizophrenia. This is the first report that offers a unified explanation of functional neuroimaging, symptoms, and outcomes. Future studies combining neuroimaging techniques and clinical assessments would elucidate schizophrenia's pathogenesis.

7.
Psychiatry Res ; 259: 77-80, 2018 01.
Article in English | MEDLINE | ID: mdl-29031167

ABSTRACT

The purpose of this study was to investigate the characteristics of central coherence in patients with anorexia nervosa (AN). 22 female patients with AN (median age = 31.50 (QD = 8.13) years) and 33 female healthy controls (HC) (median age = 28.00 (QD = 8.50) years) participated in the study. Their central coherence was assessed with the Rey Complex Figure Task (RCFT). Clinical symptoms were evaluated with the Beck Depression Inventory-II and the State-Trait Anxiety Inventory-Form JYZ. The results showed that AN patients' Central Coherence Index and accuracy scores in copy, 3-min delayed recall and 30-min delayed recall tasks of the RCFT were significantly lower than those of HC. Moreover, the significant differences in Central Coherence Index score in copy task and accuracy scores in 3-min delayed recall and 30-min delayed recall tasks remained when the effects of depression, anxiety and starvation were eliminated statistically. These findings may explain some characteristics of AN patients such as focusing on local rather than global picture in their perception of body or life.


Subject(s)
Anorexia Nervosa/diagnosis , Anorexia Nervosa/psychology , Mental Recall/physiology , Neuropsychological Tests , Psychomotor Performance/physiology , Adult , Anorexia Nervosa/epidemiology , Anxiety/diagnosis , Anxiety/epidemiology , Anxiety/psychology , Depression/diagnosis , Depression/epidemiology , Depression/psychology , Female , Humans , Psychiatric Status Rating Scales , Young Adult
8.
Psychiatry Clin Neurosci ; 71(5): 328-335, 2017 May.
Article in English | MEDLINE | ID: mdl-27973723

ABSTRACT

AIM: The purpose of this study was to elucidate determinants of quality of life (QOL) in anorexia nervosa (AN) patients. METHODS: Twenty-one female patients with AN participated in the study. QOL was assessed with the 36-Item Short Form Health Survey (SF-36), and cognitive function was evaluated using the Wisconsin Card Sorting Test Keio version, the Rey Complex Figure Test, and the Social Cognition Screening Questionnaire. Clinical symptoms were evaluated with the Beck Depression Inventory-II, the State-Trait Anxiety Inventory-Form JYZ (STAI-JYZ), and the Maudsley Obsessive Compulsive Inventory. RESULTS: The Difficulty Maintaining Set score of the Wisconsin Card Sorting Test Keio version was negatively correlated to the SF-36 Physical Component Summary. Scores of the Beck Depression Inventory-II and the STAI-JYZ State and Trait were negatively correlated to the SF-36 Mental Component Summary (MCS), and the Central Coherence Index 30-min Delayed Recall score of the Rey Complex Figure Test was positively correlated with the MCS. Stepwise regression analysis showed that the Difficulty Maintaining Set score was an independent predictor of the Physical Component Summary and scores for Central Coherence Index 30-min Delayed Recall and the STAI-JYZ Trait-predicted MCS. CONCLUSION: These results suggest that not only trait anxiety but also poor central coherence and impaired ability to maintain new rule worsen AN patients' QOL.


Subject(s)
Anorexia Nervosa/psychology , Cognition , Quality of Life/psychology , Adult , Anorexia Nervosa/complications , Anxiety/complications , Anxiety/psychology , Case-Control Studies , Female , Humans , Neuropsychological Tests , Personality Inventory , Psychiatric Status Rating Scales , Young Adult
9.
J Affect Disord ; 208: 139-144, 2017 Jan 15.
Article in English | MEDLINE | ID: mdl-27770643

ABSTRACT

BACKGROUND: Previous studies of patients with bipolar disorder (BD) using magnetic resonance spectroscopy (MRS) have shown neurophysiological abnormalities related to the glutamate (Glu)-glutamine (Gln) cycle, membrane turnover, and neuronal integrity, although the results were neither consistent nor conclusive. Recently it has been reported the Gln/Glu ratio is the most useful index, quantifying neuronal-glial interactions and the balance of glutamatergic metabolites In this MRS study, we elucidated the abnormalities of metabolites in a larger sample of patients with BD with a high-field MRI system. METHODS: Sixty-two subjects (31 patients with BD and 31 healthy controls [HC]) underwent 3T proton MRS (1H-MRS) of the anterior cingulate cortex (ACC) and left basal ganglia (ltBG) using a stimulated echo acquisition mode (STEAM) sequence. RESULTS: After verifying the data quality, 20 patients with BD and 23 age- and gender-matched HCs were compared using repeated-measures analysis of covariance (ANCOVA). Compared to the HC group, the BD group showed increased levels of Gln, creatine (Cr), N-acetyl aspartate (NAA), choline (Cho), and an increased ratio of Gln to Glu in the ACC, and increased Gln and Cho in the ltBG. These findings remained after the participants with BD were limited to only euthymic patients. After removing the influence of lithium (Li) and sodium valproate (VPA), we observed activated glutamatergic neurotransmission in the ACC but not in the ltBG. LIMITATIONS: The present findings are cross-sectional and metabolites were measured in only two regions. CONCLUSIONS: Our results support a wide range of metabolite changes in patients with BD involved in glutamatergic neurotransmission, membrane turnover, and neuronal integrity. Moreover, the elevation of Gln/Glu ratio suggested that hyperactivity of glutamatergic neurotransmission in the ACC is a disease marker for BD.


Subject(s)
Basal Ganglia/metabolism , Bipolar Disorder/diagnosis , Glutamic Acid/metabolism , Glutamine/metabolism , Gyrus Cinguli/metabolism , Magnetic Resonance Spectroscopy , Adult , Biomarkers/metabolism , Bipolar Disorder/metabolism , Case-Control Studies , Cross-Sectional Studies , Female , Humans , Magnetic Resonance Spectroscopy/methods , Male , Middle Aged
10.
Neuropsychiatr Dis Treat ; 12: 2527-2531, 2016.
Article in English | MEDLINE | ID: mdl-27785029

ABSTRACT

BACKGROUND: The purpose of this study was to investigate the characteristics of social cognition in patients with anorexia nervosa (AN). METHODS: Eighteen female patients with AN (mean age =35.4±8.6 years) and 18 female healthy controls (HC) (mean age =32.8±9.4 years) participated in the study. Their social cognition was assessed with the Social Cognition Screening Questionnaire (SCSQ). RESULTS: The results showed that total score of the SCSQ and scores of theory of mind and metacognition were significantly lower in AN group than those in HC group. Moreover, significant differences in theory of mind, metacognition, and total score of the SCSQ remained when the effects of depression, anxiety, and starvation were eliminated statistically. CONCLUSION: These results suggest that patients with AN may have difficulty inferring other people's intention and also monitoring and evaluating their own cognitive activities. Therefore, these features may explain some aspects of the pathology of AN.

11.
Int J Eat Disord ; 49(4): 402-6, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26446402

ABSTRACT

OBJECTIVE: Refeeding in patients with anorexia nervosa (AN) is associated with a risk of refeeding syndrome, which is a disruption in metabolism with a variety of features including hypophosphatemia. We evaluated the risk factors for refeeding hypophosphatemia (RH) during nutritional replenishment in Japanese patients with AN. METHODS: We retrospectively examined clinical data for 99 female inpatients (mean age 30.9 ± 10.7 years; range, 9 - 56 years). RESULTS: RH (phosphate < 2.3 mg/dL) occurred within 4.8 ± 3.7 days of hospital admission and was still observed at 28 days after admission in 21 of the 99 cases (21.2%). Oral or intravenous phosphate was given to some patients to treat or prevent RH. Patients with RH had a significantly lower body mass index, were older, and had higher blood urea nitrogen than those without RH. Severe complications associated with RH were recorded in only one patient who showed convulsions and disturbed consciousness at Day 3 when her serum phosphate level was 1.6 mg/dL. CONCLUSIONS: The significant risk factors for RH that we identified were lower body mass index, older age, and higher blood urea nitrogen at admission. No significant difference in total energy intake was seen between the RH and no RH groups, suggesting that RH may not be entirely correlated with energy intake. Precisely predicting and preventing RH is difficult, even in patients with AN who are given phosphate for prophylaxis. Thus, serum phosphate levels should be monitored for more than 5 days after admission.


Subject(s)
Anorexia Nervosa/therapy , Hypophosphatemia/etiology , Refeeding Syndrome/complications , Adolescent , Adult , Anorexia Nervosa/epidemiology , Child , Energy Intake/physiology , Female , Hospitalization/statistics & numerical data , Humans , Hypophosphatemia/epidemiology , Japan/epidemiology , Middle Aged , Refeeding Syndrome/epidemiology , Retrospective Studies , Risk Factors , Young Adult
12.
Gen Hosp Psychiatry ; 36(4): 449.e3-5, 2014.
Article in English | MEDLINE | ID: mdl-24725972

ABSTRACT

We report a 59-year-old man with isolated adrenocorticotropin (ACTH) deficiency. The patient presented with sudden onset of delusions and hallucinations at the age of 54, which resolved gradually without treatment. Subsequently, the patient manifested stereotypy, wandering, hypobulia, and autistic symptoms, and was treated with antipsychotics for 1 year without any improvement. He suffered from neuroleptic malignant syndrome-like symptoms at the age of 59. A thorough endocrine assessment revealed isolated ACTH deficiency. After hydrocortisone supplementation, the physical and psychiatric symptoms improved dramatically. Clinicians should consider this rare disease when diagnosing patients with refractory psychiatric symptoms and unique physical symptoms of isolated ACTH deficiency.


Subject(s)
Adrenocorticotropic Hormone/deficiency , Anti-Inflammatory Agents/pharmacology , Endocrine System Diseases/complications , Endocrine System Diseases/diagnosis , Genetic Diseases, Inborn/complications , Genetic Diseases, Inborn/diagnosis , Hydrocortisone/pharmacology , Hypoglycemia/complications , Hypoglycemia/diagnosis , Psychotic Disorders/etiology , Anti-Inflammatory Agents/administration & dosage , Endocrine System Diseases/drug therapy , Genetic Diseases, Inborn/drug therapy , Humans , Hydrocortisone/administration & dosage , Hypoglycemia/drug therapy , Male , Middle Aged , Neuroleptic Malignant Syndrome/diagnosis , Psychotic Disorders/drug therapy , Treatment Outcome
13.
Neurosci Lett ; 401(1-2): 1-5, 2006 Jun 19.
Article in English | MEDLINE | ID: mdl-16533563

ABSTRACT

Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor that promotes several functions of neurons and modulates neurotransmissions. It has been reported that there are alterations of BDNF levels in schizophrenic brains and that BDNF gene expressional changes would be responsible for the etiology of schizophrenia. Recent studies have shown that a variation of BDNF gene (Val66Met polymorphism) affects the function of neurons, and is associated with several neurological and psychiatrical disorders. We investigated the relationship between BDNF Val66Met polymorphism and the onset age as well as levels of clinical symptoms in 159 of chronic schizophrenia in-patients diagnosed by DSM-IV. The mean onset ages were 27.5+/-9.5 for BDNF Val/Val, 25.5+/-7.4 for BDNF Val/Met and 22.9+/-6.0 for BDNF Met/Met and this polymorphism was significantly associated with age at onset (P=0.023). The mean Brief Psychiatric Rating Scale scores (BPRS) were significantly different among those three groups (P=0.003). No significant differences were demonstrated comparing the BDNF genotype distributions of positive and negative family history (P=0.21). Our investigation indicates that the BDNF gene Val66Met polymorphism is related to the onset age of schizophrenia and the levels of clinical symptoms that remain after long-term antipsychotic treatment.


Subject(s)
Amino Acid Substitution/genetics , Brain-Derived Neurotrophic Factor/genetics , Genetic Predisposition to Disease/genetics , Polymorphism, Genetic/genetics , Schizophrenia/genetics , Schizophrenia/physiopathology , Adult , Age of Onset , Aged , Antipsychotic Agents/pharmacology , Brain/metabolism , Brain/physiopathology , Brain Chemistry/genetics , DNA Mutational Analysis , Drug Resistance/genetics , Female , Gene Frequency , Genetic Testing , Genotype , Humans , Male , Methionine/genetics , Middle Aged , Schizophrenia/drug therapy , Valine/genetics
14.
Neuropsychobiology ; 53(2): 70-6, 2006.
Article in English | MEDLINE | ID: mdl-16511337

ABSTRACT

BACKGROUND: The Wisconsin Card Sorting Test (WCST) is a neuropsychological test to evaluate the function of the prefrontal cortex (PFC). However, inconsistent results have been reported concerning whether this task activates the PFC symmetrically or asymmetrically. OBJECTIVES: To investigate the brain activation in the PFC during the WCST, we examined blood oxygenation changes of healthy subjects by using multichannel near-infrared spectroscopy (NIRS). METHODS: Subjects were 32 healthy volunteers, 18 males and 14 females. The WCST was administered using a computerized version, and the hemodynamic changes of the PFC during the WCST were measured by a 24-channel NIRS system. RESULTS: A bilateral increase in oxygenated hemoglobin (oxyHb) was observed in the PFC in 20 subjects during the WCST. However, 5 subjects showed predominant activation on the left side and 3 subjects one on the right side. No oxyHb change was observed in 4 subjects, although they had good performances in the WCST. CONCLUSIONS: These results directly confirmed that the PFC was activated during the WCST in vivo by using the optical technique and suggested that the distribution of the activation in the PFC is different among healthy individuals.


Subject(s)
Brain Mapping , Decision Making/physiology , Oxyhemoglobins/metabolism , Pattern Recognition, Visual/physiology , Prefrontal Cortex/physiology , Adult , Brain Mapping/instrumentation , Cerebrovascular Circulation/physiology , Female , Functional Laterality/physiology , Humans , Male , Middle Aged , Neuropsychological Tests , Prefrontal Cortex/blood supply , Psychomotor Performance/physiology , Reference Values , Reproducibility of Results , Spectroscopy, Near-Infrared
15.
J Med Invest ; 52 Suppl: 302-3, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16366522

ABSTRACT

To investigate the brain activation in the prefrontal cortex (PFC) during mental works, we examined blood oxygenation changes of healthy subjects by using multi channel near infrared spectropcopy (NIRS). It was directly confirmed that the PFC was activated during mental tasks in vivo and it was suggested that distribution of the activation in the PFC is different among healthy individuals.


Subject(s)
Hemodynamics , Mental Processes/physiology , Prefrontal Cortex/blood supply , Spectroscopy, Near-Infrared/methods , Functional Laterality , Health Status , Hemoglobins/metabolism , Humans , Neuropsychological Tests , Oxygen/blood , Oxyhemoglobins/analysis , Prefrontal Cortex/metabolism , Spectroscopy, Near-Infrared/instrumentation , Volunteers
16.
J Biol Chem ; 278(12): 10067-72, 2003 Mar 21.
Article in English | MEDLINE | ID: mdl-12531904

ABSTRACT

T-protein, a component of the glycine cleavage system, catalyzes a tetrahydrofolate-dependent reaction. Previously, we reported a conformational change of Escherichia coli T-protein upon interacting with E. coli H-protein (EH), showing an important role for the N-terminal region of the T-protein in the interaction. To further investigate the T-protein catalysis, the wild type (ET) and mutants were subjected to limited proteolysis. ET was favorably cleaved at Lys(81), Lys(154), Lys(288), and Lys(360) by lysylendopeptidase and the cleavages at Lys(81) and Lys(288) were strongly prevented by EH. Although ET was highly resistant to trypsinolysis, the mutant with an N-terminal 7-residue deletion (ETDelta7) was quite susceptible and instantly cleaved at Arg(16) accompanied by the rapid degradation of the resulting C-terminal fragment, indicating that the cleavage at Arg(16) is the trigger for the C-terminal fragmentation. EH showed no protection from the N-terminal cleavage, although substantial protection from the C-terminal fragmentation was observed. The replacement of Leu(6) of ET with alanine resulted in a similar sensitivity to trypsin as ETDelta7. These results suggest that the N-terminal region of ET functions as a molecular "hasp" to hold ET in the compact form required for the proper association with EH. Leu(6) seems to play a central role in the hasp function. Interestingly, Lys(360) of ET was susceptible to proteolysis even after the stabilization of the entire molecule of ET by EH, indicating its location at the surface of the ET-EH complex. Together with the buried position of Lys(81) in the complex and previous results on folate binding sites, these results suggest the formation of a folate-binding cavity via the interaction of ET with EH. The polyglutamyl tail of the folate substrate may be inserted into the bosom of the cavity leaving the pteridine ring near the entrance of the cavity in the context of the catalytic reaction.


Subject(s)
Amino Acid Oxidoreductases , Carrier Proteins/physiology , Escherichia coli Proteins/chemistry , Hydroxymethyl and Formyl Transferases/chemistry , Aminomethyltransferase , Carrier Proteins/chemistry , Glycine Decarboxylase Complex H-Protein , Glycine Dehydrogenase (Decarboxylating) , Hydroxymethyl and Formyl Transferases/metabolism , Protein Conformation , Trypsin/pharmacology
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