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Biomedical subjects

T Kakuma

Publications and source records attributed to T Kakuma.

At least 55 records · Page 3Linked to original sources

Enhanced expression of uncoupling protein 2 gene in rat white adipose tissue and skeletal muscle following chronic treatment with thyroid hormone.

Evidence is rapidly emerging which suggests that uncoupling protein 2 (UCP2), by virtue of its ubiquitous expression, may be important for determining basal metabolic rate. To assess the functional modulation of UCP2 gene expression in relation to body weight control, we examined the effects of hyperthyroid state induced by chronic treatment with triiodothyronine (T3) on UCP2 mRNA expression in male rats. Daily subcutaneous injection of T3 (37 pmol/100 g body weight) for 7 days increased UCP2 mRNA expression in brown adipose tissue (BAT), white adipose tissue (WAT) and the soleus muscle 1.6-, 1.6- and 1.7-fold compared to the controls, respectively, and increased UCP1 mRNA expression in BAT 1.2-fold. In contrast, the same treatment with T3 decreased both ob mRNA expression in WAT and plasma leptin level 0.5-fold for each. The present results suggest that T3 may directly increase UCP2 expression independently of leptin action.

Adipose Tissue↗

Pain assessment in self-injurious patients with borderline personality disorder using signal detection theory.

Signal detection theory measures of thermal responsivity were examined to determine whether differences in reported pain experienced during self-injurious behavior in female patients with borderline personality disorder (BPD) are explained by neurosensory factors and/or attitudinal factors (response bias). Female patients with BPD who do not experience pain during self-injury (BPD-NP group) were found to discriminate more poorly between noxious thermal stimuli of similar intensity, low P(A), than female patients with BPD who experience pain during self-injury (BPD-P group), female patients with BPD who do not have a history of self-injury (BPD-C group), and age-matched normal women. The BPD-NP group also had a higher response criterion, B (more stoical) than the BPD-C group. These findings suggest that 'analgesia' during self-injury in patients with BPD is related to both neurosensory and attitudinal/psychological abnormalities.

Adolescent↗

Organization and expression of the mouse MTH1 gene for preventing transversion mutation.

An enzyme, 8-oxo-7,8-dihydrodeoxyguanosine triphosphatase (8-oxo-dGTPase), is present in various organisms and plays an important role in the control of spontaneous mutagenesis. The enzyme hydrolyzes 8-oxo-dGTP, an oxidized form of dGTP, to 8-oxo-dGMP, thereby preventing the occurrence of A:T to C:G transversion, caused by misincorporation. We isolated the mouse genomic sequence encoding the enzyme and elucidated its structure. The gene, named MTH1 for mutT homologue 1, is composed of at least five exons and spans approximately 9 kilobase pairs. A genomic region containing the pseudogene was also isolated. The promoter region for the gene is GC-rich, contains many AP-1 and AP-2 recognition sequences, and lacks a typical TATA box. Primer extension and S1 mapping analyses revealed the existence of multiple transcription initiation sites, among which a major site was defined as +1. The putative promoter region was placed upstream of the chloramphenicol acetyltransferase reporter gene, and control of expression of the gene was examined by introducing the construct into mouse NIH 3T3 cells. Deletion analysis indicated that a sequence from -321 to +9 carries the basic promoter activity while an adjacent region, spanning from +352 to +525 stimulates the frequency of transcription.

3T3 Cells↗

Interpersonal perceptions of depressed and borderline inpatients.

Distortions in interpersonal perceptions among patients with borderline personality disorder (BPD) were explored to investigate the validity of object relations theories. Depressed patients with BPD were compared to patients with major depressive disorder (MD) without BPD. Subjects were 77 male and female inpatients (BPD = 55, MD = 22). The mean ages were 30.5 for BPD subjects and 36.3 for MD subjects. Perceptions of patients, relatives, and interviewers were compared on the following measures: Structural Analysis of Social Behavior, Perceived Criticism Scale, and Camberwell Family Interview. Findings are consistent with object relations theory. BPD patients saw themselves as hostile, labile, and unstable. MD patients avoid acknowledging and responding to relatives criticallity.

Adult↗

Clinically defined vascular depression.

OBJECTIVE: The authors' goal was to examine the clinical presentation of a group of depressed elderly patients with clinically defined risk factors for vascular depression compared with a group of elderly depressed patients without such risk factors. METHOD: Cognitive deficits, disability, and depressive symptoms were examined in 33 consecutively recruited elderly patients defined as having vascular depression and 32 patients defined as having nonvascular depression according to their scores on the Cumulative Illness Rating Scale-Geriatrics. RESULTS: The patients with vascular depression had greater overall cognitive impairment and disability than those with nonvascular depression. Fluency and naming were more impaired in patients with vascular depression, and they had more retardation and less agitation as well as less guilt feelings and greater lack of insight. CONCLUSIONS: The symptoms of vascular depression are consistent with lesions that may damage striato-pallido-thalamo-cortical pathways and other areas. The concept of vascular depression can provide the impetus for investigations of prevention and treatment of cerebrovascular disease and for studies of the course of vascular depression and selection of antidepressants.

Age of Onset↗

Brainstem evoked response abnormalities in late-life depression with vascular disease.

OBJECTIVE: The purpose of this study was to examine whether the brainstem evoked responses of geriatric depressed patients with vascular disease show greater changes in wave V latency after increased stimulation than do responses of geriatric depressed patients without vascular disease and elderly comparison subjects with and without vascular disease. METHOD: Geriatric patients with unipolar depression (N = 53) were recruited from a university psychiatric hospital. Elderly comparison subjects (N = 23) were recruited through advertisements. All subjects were assessed for depressive symptoms, cognitive performance, overall medical burden, vascular disease, and disability. Brainstem evoked response was elicited at stimulation rates of 11.4 and 80.0 clicks/sec. RESULTS: The interaction between depression and vascular disease had a significant effect on change in wave V latency. This effect was synergistic, more than an additive effect. Post hoc comparisons showed that the depressed patients with vascular disease had greater changes in wave V latency that did the depressed patients without vascular disease, comparison subjects with vascular disease, and comparison subjects without vascular disease. Linear discriminant function analysis showed that 82% of the subjects with abnormal changes in wave V latency (sensitivity: 75%, specificity: 81%) could be identified on the basis of ratings for depression and vascular disease. CONCLUSIONS: Demyelination afflicting the pons and mesencephalon may explain the greater change in wave V latency for the brainstem evoked response in depressed patients with vascular disease. Further studies combining brainstem evoked response with brain imaging may determine whether depression develops only after vascular disease leads to demyelination.

Aged↗

The limits of history-taking in geriatric depression.

The authors assessed the limits of reliable history-taking in depressed elderly patients (N = 20) with some cognitive impairment. Each subject and an informant was interviewed with structured instruments by two trained raters. An expert panel formed consensus judgments after reviewing information reported by the patients, the informants, and each of the clinical raters. Intraclass correlation between the two raters was 0.99 for the duration of depressive episodes and 0.88 for age at onset. The raters agreed on the duration of major depressive episodes in 85% of cases and on age at onset in 80% of cases. The duration of previous depressive episodes and age at depression onset cannot always be determined reliably even when informants and structured interviews are used. Greater difficulties may be encountered in patients with minor depression or chronic intermittent depression and early-onset depression. Clinicians should obtain history from as many reliable sources as possible and critically evaluate this information while considering the entire clinical picture. The aggregate kappa statistic can provide a clinically meaningful way of assessing interrater reliability of psychopathological constructs for which several definitions are used.

Age of Onset↗

Pain and self-injury in borderline patients: sensory decision theory, coping strategies, and locus of control.

Fifteen women with borderline personality disorder who do not experience pain during self-injury were found to discriminate more poorly between imaginary painful and mildly painful situations, to reinterpret painful sensations (a pain-coping strategy related to dissociation), and to have higher scores on the Dissociative Experiences Scale than 24 similar female patients who experience pain during self-injury and 22 age-matched normal women. "Analgesia' during self-injury in borderline patients may be related to a cognitive impairment in the ability to distinguish between painful and mildly painful situations, as well as to dissociative mechanisms.

Adaptation, Psychological↗

Recovery in geriatric depression.

BACKGROUND: Clinical characteristics of depression, age at illness onset, medical burden, disability, cognitive impairment, lack of social support, and poor living conditions may influence the course of depression. This study investigates the timetable of recovery and the role of the above factors in predicting recovery in elderly patients with major depression. METHODS: Recovery was studied in 63 elderly (age >63 years) and 23 younger patients with depression who were followed up for an average of 18.2 months (SD, 13.1 months) under naturalistic treatment conditions. Diagnosis was assigned according to Research Diagnostic Criteria after administration of the Schedule for Affective Disorders and Schizophrenia. The Longitudinal Follow-up Interval Examination was used to identify recovery. RESULTS: The recovery rate of depressed elderly patients was similar to that of younger depressed patients. In the elderly patients, age, antidepressant treatment, age at onset, and chronicity of episode were significantly associated with time to recovery since entry. Among these parameters, late age at onset was the strongest predictor of slow recovery. In younger patients, long time to recovery was predicted by weak social support, younger age, cognitive impairment, and low intensity of antidepressant treatment. In the elderly, the intensity of antidepressant treatment began to decline within 16 weeks from entry and approximately 10 weeks prior to recovery. CONCLUSIONS: These findings challenge the view that geriatric depression has a worse outcome than depression in younger adults. However, depressed patients with onset of first episode in late life may be at higher risk for chronicity. Antidepressant treatment prescribed by clinicians may decline prior to recovery despite evidence that high treatment intensity is effective in preventing relapse.

Adult↗

Predictors of fall-related injuries among community-dwelling elderly people with dementia.

To determine the annual incidence of fall-related injuries among community-dwelling elderly people with dementia and to identify the factors predicting those likely to sustain such injuries, we conducted a cohort study with a one-year follow-up. As predicting factors, we paid particular attention to behavioural problems and difficulties in helping with activities of daily living based on the Assessment of Basic Care for the Demented (ABCD) scale. Thirty-five of 86 final study subjects and nine of 98 final control subjects sustained fall-related injuries. Significant factors associated with fall-related injuries to demented elderly subjects were ABCD score (adjusted odds ratio 0.73, 95% confidence interval 0.60-0.89), history of falls in the past year (3.65, 1.34-9.95), and Barthel index score (1.04, 1.00-1.08). This highlights the predictive value of better physical function but more difficult care status in relation to ADL for fall-related injuries.

Accidental Falls↗

Prevalence of dementia and distribution of ApoE alleles in Japanese centenarians: an almost-complete survey in Yamanashi Prefecture, Japan.

OBJECTIVE: To determine the prevalence and types of dementia in centenarians and to examine whether the ApoE epsilon 4 allele has significant impact on the development of Alzheimer's disease (AD) in the population. DESIGN: Cross-sectional study and a 6-month prospective study. SETTING: Yamanashi Prefecture, Japan. PARTICIPANTS: Forty-seven centenarians participated in the study to determine the prevalence and types of dementia. Thirty-three of the 47 participated in the study of ApoE genotyping. As controls, 224 demented older adults participated in the genetic study. Their age at onset was < 90 years. OUTCOMES: Prevalence of dementia based on DSM-III-R; types of dementia based on NINCDS-ADRDA and ICD-10; distribution on ApoE alleles in the centenarians and in the controls; and the 6-month mortality rate of the subjects. MAIN RESULTS: Of 47 centenarians, 70.2% had dementia, and AD accounted for the majority (75.8%) of the dementia cases. The distribution of ApoE alleles in all the subjects and the AD subjects was epsilon 2: 4.6% vs. 0%; epsilon 3: 90.1% vs. 94.1%; epsilon 4: 4.6% vs. 5.9%. The frequency of the epsilon 4 allele in the AD patients showed a tendency to decrease with increasing age, ranging from 38% for those with an age at onset of < 60 years to 22% for those with an age at onset of ranging from 80 to 89 years. The 6-month mortality rate was 27% (9/33) for the demented centenarians, whereas none of the 14 nondemented centenarians died. CONCLUSION: This almost-complete survey, conducted in a prefecture of Japan, revealed a high prevalence of dementia in centenarians. The ApoE epsilon 4 allele does not have an impact on the development of AD in centenarians.

Age Distribution↗

Hypoxic contraction of contractile interstitial cells isolated from bovine lung.

Although contractile interstitial cells (CIC) in the alveolar septum have been suggested to be involved in hypoxic pulmonary vasoconstriction (HPV), direct demonstration of cellular contraction under hypoxia has been lacking. To achieve this, we purified CIC from collagenase-dissociated bovine lung cells and examined the response of these cells to hypoxia. Prostaglandin (PG) F synthase served as a marker of CIC, and the isolated PGF synthase-positive cells were shown to preserve the ultrastructural features characteristic of CIC, most notably bundles of microfilaments. Isolated CIC seeded onto collagen gel disks became embedded and formed a lattice network with collagen fibrils. Exposure of these CIC-bearing gels to hypoxia (PO2 = 20-40 Torr) evoked a reversible reduction in gel volume, as assessed by measuring the surface area of the gel disks photographically. Thus CIC were shown to contract under hypoxia, providing the supportive evidence for the involvement of CIC in HPV.

Animals↗

Disability in geriatric depression.

OBJECTIVE: The authors' purpose was to identify the relationship of disability to clinical measures that are part of a comprehensive psychiatric examination of depressed elderly patients. METHOD: The disability of 75 elderly inpatients and outpatients with major depression whose cognitive function ranged from normality to mild dementia was assessed with the Philadelphia Multilevel Assessment Instrument. Age at onset of depression, chronicity of depression, severity of depression, cognitive impairment, medical burden, social support and living environment were assessed with standardized instruments. RESULTS: Impairment in instrumental activities of daily living was significantly associated with advanced age, severity of depression, and medical burden. The relationship of depressive symptoms to impairment in instrumental activities of daily living was not influenced by age or medical burden. Anxiety and depressive ideation as well as retardation and weight loss were significantly associated with impairment in instrumental activities of daily living. Interviewer-rated global disability was associated with advanced age at onset of depression, medical burden, and overall cognitive impairment. Specifically, a disturbance in initiation and perseveration was significantly related to global disability. CONCLUSIONS: Impairment in instrumental activities of daily living appears to be a relatively independent dimension of health status that is related to depressive symptoms, particularly anxiety and depressive ideation as well as retardation and weight loss. Global disability may be associated with impairment in initiation and perseveration and with late onset of depression. These findings provide a basis for studies investigating whether psychotherapy aimed at depressive ideation and rehabilitation efforts focused on instrumental activities of daily living can improve the outcome of geriatric depression.

Activities of Daily Living↗

Age at onset of geriatric depression and sensorineural hearing deficits.

Comorbidity of sensorineural hearing deficits and both depressive states and dementia in late life provided the rationale for this investigation. Cognitively intact geriatric major depressives (n = 43) were assessed for depressive symptoms, cognitive performance, and delusions while symptomatic, and following treatment, when audiometry was performed. Late-onset depressed patients (LOD) had more hearing deficits compared to early-onset depressives (EOD). Age at onset of depression was found to have a significant effect on Pure-Tone Thresholds for 0.5-4.0 kHz and on Word Recognition in Noise in the better ear (0.001 < p < 0.031; ANCOVA). Criteria for neural deficit were met more frequently in LODs compared to EODs, although this was attributable to the older age of LOD. Additional investigations can contribute to our understanding of the relationship between forms of hearing loss and both the course of geriatric depression and its relationship to dementia.

Age of Onset↗

Mouse MTH1 protein with 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphatase activity that prevents transversion mutation. cDNA cloning and tissue distribution.

8-Oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate (8-oxo-dGTP) is formed in the nucleotide pool of a cell during normal cellular metabolism, and when it is incorporated into DNA causes mutation. Organisms possess 8-oxo-dGTPase, an enzyme that specifically degrades 8-oxo-dGTP to 8-oxo-dGMP. We isolated cDNA for mouse 8-oxo-dGTPase, using as a probe human MTH1 (Escherichia coli mutT homolog) cDNA. The nucleotide sequence of the cDNA revealed that the mouse MTH1 protein (molecular weight of 17,896) comprises 156 amino acid residues. When the cDNA for mouse 8-oxo-dGTPase was expressed in E. coli mutT- mutant cells devoid of their own 8-oxo-dGTPase activity, an 18-kDa protein, which is cross-reactive with an anti-human MTH1 antibody, was formed. In such cells, the level of spontaneous mutation frequency that was elevated reverted to normal. High levels of 8-oxo-dGTPase activity were found in liver, thymus, and large intestine, whereas all other organs examined contained smaller amounts of the enzyme. In embryonic stem cells, an exceedingly high level of the enzyme was present.

Amino Acid Sequence↗

cDNA and genomic sequences for rat 8-oxo-dGTPase that prevents occurrence of spontaneous mutations due to oxidation of guanine nucleotides.

The enzyme, 8-oxo-7,8-dihydrodeoxyguanosine triphosphatase (8-oxo-dGTPase), is present in various organisms and plays an important role in control of spontaneous mutagenesis. This enzyme degrades 8-oxoguanine-containing deoxyribonucleoside triphosphate, a potentially mutagenic substrate for DNA synthesis, to the corresponding monophosphate. To obtain appropriate probes for expression of the gene in various tissues and also to construct appropriate experimental models for carcinogenesis, we cloned cDNA for rat 8-oxo-dGTPase and elucidated its structure. The nucleotide sequence of the cDNA revealed that the rat 8-oxo-dGTPase protein is composed of 156 amino acid residues. The molecular weight of rat 8-oxo-dGTPase, calculated from the predicted amino acid sequence, was 18,006, and the 8-oxo-dGTPase protein of this size was detected when the cDNA was expressed in 8-oxo-dGTPase-deficient Escherichia coli mutT- cells. The predicted amino acid sequence of the rat 8-oxo-dGTPase has a close homology with those of human and bacterial counterparts. Using the cDNA as a probe, part of the rat gene for 8-oxo-dGTPase was isolated and was found to consist of at least three exons and spanned about 10 kb. A genomic region containing the pseudogene was also isolated.

Amino Acid Sequence↗

Racial differences in treatment of psychiatric inpatients.

OBJECTIVE: The study examined several aspects of inpatient psychiatric treatment to determine if differences existed between treatment of African-American and white patients. METHODS: Using a structured chart review, data were collected on 76 African-American and 88 white patients consecutively admitted to an acute inpatient setting with a principal axis I diagnosis of a major mood or psychotic disorder. Racial differences in treatment were examined using analysis of variance and logistic regression to assess the effects of diagnosis and socioeconomic status. RESULTS: Nonpsychotic African-American patients had shorter lengths of stay than white patients with similar disorders. White patients were more likely to be on one-to-one observational status. Clinicians were more likely to order urine drug screens for African-American patients with high socioeconomic status than for comparable white patients. African-American patients with schizophrenic disorders received higher neuroleptic dosages than white patients with similar diagnoses. CONCLUSIONS: Most racial differences cited in earlier studies of psychotic patients were not found or were not statistically significant once socio-economic status and diagnosis were accounted for. However, racial differences related to the detection, phenomenology, treatment, and course of psychotic disorders and the diagnosis and management of alcohol and drug use disorders and personality disorders were found.

Adolescent↗