Biomedical subjects

T Kakuma

Publications and source records attributed to T Kakuma.

At least 19 recordsLinked to original sources

PubMed1999

Decreased dopamine beta-hydroxylase activity in unipolar geriatric delusional depression.

BACKGROUND: Decreased dopamine beta-hydroxylase (DBH) activity has been reported in unipolar psychotic depression. DBH comparisons between elderly delusional and nondelusional depressives and controls and determination of whether pretreatment group differences persist have not been reported. Our objective was to compare DBH activity in elderly delusional major depressives with that of nondelusional depressives and normal control subjects before and after hospital treatment. METHODS: Enzyme activity was assessed after hospital admission. A subsample had predischarge assessments. Treatment was not controlled but accounted for in analyses. Electroconvulsive therapy subjects were medication-free for posttreatment assays. RESULTS: Baseline and predischarge DBH assays were lower in subjects with delusional depression than in either comparison group. Despite high intraindividual correlation, treatment was associated with significant increases in activity in the clinical groups. CONCLUSIONS: Patients with late-life delusional depression have lower DBH activity before and after hospital treatment than age-matched nondelusional patients or normal controls.

Age of Onset↗

PubMed1999

Tumor necrosis factor-alpha regulates in vivo expression of the rat UCP family differentially.

A family of uncoupling proteins (UCPs), free fatty acid anion transporters, plays a crucial role in energy homeostatic thermoregulation. Tumor necrosis factor-alpha (TNF-alpha), a member of the cytokine family, is well known as an endogenous pyrogen. To evaluate the interaction of TNF-alpha with UCPs in thermogenesis, effects of TNF-alpha on rat UCP gene expression were examined in intrascapular brown adipose tissue (BAT), epididymal white adipose tissue (WAT) and soleus muscle (Muscle). Administration of TNF-alpha elevated rectal temperature by 0.7 degree C as well as serum leptin which peaked at 6 h, compared with saline controls. BAT UCP1 mRNA expression was increased by 1.2-fold at 6 h after the TNF-alpha treatment and decreased by 0.8-fold at 16 h after the treatment. In contrast to UCP1 expression in BAT, UCP2 mRNA expressions in BAT, WAT, and Muscle was increased to reach maximum levels of 1.3-, 1.6- and 1.8-fold, respectively, at 16 h after the treatment. UCP3 mRNA in Muscle, but not in BAT or WAT, was exclusively up-regulated by 1.7-fold at 16 h after the treatment. These results indicate that TNF-alpha up-regulates UCP gene expression differentially and tissue dependently, and add novel insights into thermogenesis under conditions of malignancy and inflammation.

Adipose Tissue↗

PubMed1999

Induction of rat uncoupling protein-2 gene treated with tumour necrosis factor alpha in vivo.

BACKGROUND: The cytokine tumour necrosis factor (TNF) alpha has been reported to induce metabolic abnormalities such as anorexia and thermogenesis. To investigate functional modulators of uncoupling protein-2 (UCP2) gene expression, we examined the effects of TNF-alpha on UCP2 mRNA expression in rats. METHODS: Mature male Wistar King A (WKA) rats at 10-11 weeks of age were treated with recombinant human TNF-alpha at a dose of 0.6 nmol 100 g-1 body weight by intraperitoneal administration. RESULTS: TNF-alpha treatment induced an increase in UCP2 mRNA expression in broadly distributed tissues including brown adipose tissue (BAT), white adipose tissue (WAT) and skeletal muscle, and an elevation of ob gene mRNA expression in WAT. After the TNF-alpha treatment, an increase in plasma leptin concentration occurred in an ob gene-dependent manner, accompanied by an anorectic effect. CONCLUSION: The present results provide evidence for a new regulatory loop involving TNF-alpha and UCP2, and add novel insights into the regulatory mechanisms of energy homeostasis.

Adipose Tissue↗

PubMed1999

Early pregnancy human chorionic gonadotropin (hCG) isoforms measured by an immunometric assay for choriocarcinoma-like hCG.

Human chorionic gonadotropin (hCG) exhibits molecular heterogeneity in both its protein and carbohydrate moieties. This communication describes changes in hCG isoforms detected directly in clinical samples. These isoforms, quantified in blood or urine specimens, show a progression of change throughout normal pregnancy. Early pregnancy produces a type of hCG that resembles, in terms of immunoreactivity, a major form of hCG excreted in choriocarcinoma. The isoforms predominate for the first 5-6 weeks of gestation and then diminish, being replaced with the hCG isoforms which predominate throughout the remainder of pregnancy. The alteration in hCG isoform content occurs in both blood and urine. The progression of isoforms is best delineated by calculating the change in the ratio of the two forms, as many hCG assays either do not detect or fail to discriminate among these isoforms. An analogous pattern of hCG isoforms was observed in patients with in vitro fertilization pregnancies. hCG isolated from the pituitary displayed binding characteristics similar to those of the hCG derived from normal pregnancy urine. The early pregnancy hCG isoforms appear to have a differential expression in normal pregnancy as opposed to pregnancies which will not carry to term, suggesting that a determination of the relative balance of hCG isoforms may have diagnostic application in predicting pregnancy outcome.

Biomarkers↗

PubMed1999

Evaluation of nicked human chorionic gonadotropin content in clinical specimens by a specific immunometric assay.

We report the development and characterization of an IRMA for the direct measurement of nicked human chorionic gonadotropin (hCGn) in blood and urine. hCGn derived from a reference preparation of hCG used as an immunogen elicits monoclonal antibodies (mAbs) with enhanced recognition of human luteinizing hormone epitopes. The most specific assay for pregnancy hCGn is an IRMA composed of one mAb to choriocarcinoma-derived hCGn (C5) and a second mAb developed from immunization with normal-pregnancy hCGn. This assay was used to evaluate hCGn profiles in normal, in vitro fertilization, Down syndrome, and ectopic pregnancies. In all pregnancies, hCGn was usually present in much lower concentrations than the non-nicked hCG isoform. Our results suggest that some form of physical separation from the overwhelming quantities of non-nicked hCG present in clinical specimens will be required before accurate immunochemical estimations of hCGn can be made.

Abortion, Spontaneous↗

PubMed1998

Peripheral serotonin measures in prepubertal psychiatric inpatients and normal children: associations with suicidal behavior and its risk factors.

BACKGROUND: This study reports relationships between suicidal behavior and its risk factors in prepubertal children and whole blood and platelet serotonin-related measures. METHODS: Seventy-five prepubertal psychiatric inpatients including 23 (30.7%) nonsuicidal, 32 (42.7%) with suicidal ideation, and 20 (26.6%) with a suicide attempt were compared to 35 normal prepubertal controls with regard to platelet serotonin content, serotonin-amplified platelet aggregation, and whole blood tryptophan. RESULTS: Mean whole blood tryptophan content was significantly lower among inpatient children with a recent suicide attempt than among normal controls or inpatients with suicidal ideation (F = 3.94, df = 3.54, p < or = .01). Inpatient children with a mood disorder had significantly higher platelet serotonin content than inpatients without a mood disorder (F = 3.86, df = 2.80, p < or = .03). Racial/ethnic differences were also observed for inpatients and normal controls, with whites having significantly lower levels of platelet serotonin (expressed as ng/mL blood or ng/10(9) platelets) than blacks or Latinos. Blacks had significantly higher levels of whole blood tryptophan than other racial/ethnic groups. CONCLUSIONS: The results suggest that whole blood tryptophan and platelet serotonin content should be studied for their predictive validity as risk factors for suicidal behavior in youth while controlling for racial/ethnic differences.

Attention Deficit and Disruptive Behavior Disorder↗

PubMed1998

Novel mutation of the DAX1 gene in a patient with X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism.

X-linked adrenal hypoplasia congenita (AHC) is characterized by primary adrenal insufficiency and is frequently associated with hypogonadotropic hypogonadism (HHG). Mutations of the DAX1 gene have been reported in patients with AHC and HHG. We found a novel DAX1 mutation in our patient. Sequence analysis of the patient's DAX1 demonstrated a 1-bp (G) deletion at codon 49 in exon 1. The mutation shifts the reading frame, resulting in completely different amino acid sequences from codon 49 to the premature stop codon at 84. The G was present at this position in the sequences of the father and 2 younger brothers. Direct sequence and single-strand conformation polymorphism analyses of polymerase chain reaction fragments revealed that the mutation at codon 49 was heterozygously present in the mother's DAX1 gene. The codon 84 is located in the first half of the DNA binding domain, and the mutation site is closer to the N-terminus than those in previously reported cases. The onset of adrenal insufficiency in the neonatal period as seen in our patient has also been reported in other patients with different DAX1 mutations, especially in a patient with DAX1 protein lacking 11 amino acids at the C-terminus. Therefore, it is less likely that position of termination codons correlate to clinical manifestations.

Adrenal Glands↗

PubMed1998

Molecular cloning of rat uncoupling protein 2 cDNA and its expression in genetically obese Zucker fatty (fa/fa) rats.

We isolated rat UCP2 cDNA, which has been proposed to play an important role in mammalian thermogenesis and body weight regulation. The nucleotide sequence of the cDNA revealed that the rat UCP2 protein is composed of 309 amino acid residues, and is 99% and 95% identical to the mouse and human proteins, respectively. The molecular weight of rat UCP2, calculated from the predicted amino acid sequence, was 33,369, and the UCP2 protein of this size was detected when the cDNA was expressed in vitro. Northern blot analysis revealed that the corresponding mRNA is approximately 1.7 kb in size, and is expressed in a variety of rat organs, with predominant expression in the heart, lung and spleen. UCP2 mRNA levels in the heart, liver, muscle and epididymal adipose tissue of Zucker fatty (fa/fa) rats were comparable to those in the lean littermates, while ob mRNA level markedly increased in the epididymal adipose tissue of Zucker (fa/fa) rats.

Amino Acid Sequence↗

PubMed1998

Differential urinary gonadotrophin profiles in early pregnancy and early pregnancy loss.

Early pregnancy loss (EPL), detected by patterns of human chorionic gonadotrophin (hCG) in urine, is the biomarker employed in investigations of the impact of personal, workplace or environmental reproductive toxins on human fertility. An issue central to these studies is what, in terms of urinary hCG expression, constitutes an EPL. This report describes the urinary molecular forms of hCG expressed in menstrual cycles in which a normal pregnancy was conceived, or an EPL occurred, or no apparent conception occurred. Qualitative and significant quantitative differences in the expression of hCG-associated analytes were found between normal pregnancy cycles and EPL cycles. Discriminant analysis calculation based on mole fractions of the different hCG-associated molecules afforded 91 per cent and 80 per cent correct classification of clinical pregnancy cycles and EPL cycles, respectively. Although hCG-associated molecules unique to either EPL or normal pregnancy were not found, what is thought to be an early form of hCG is expressed both at a high frequency and at a significantly higher concentration in early normal pregnancy when compared with EPL. The relative absence of this molecule very early in pregnancy may signal a pregnancy loss.

Abortion, Spontaneous↗

PubMed1998

Suicidal children grow up: relations between family psychopathology and adolescents' lifetime suicidal behavior.

Standard family history and family study methods were used with 650 first- and 1174 second-degree biological relatives of 133 adolescents who were studied initially 6 to 8 years ago. They included 69 prepubertal children considered at risk for suicidal behavior and 64 prepubertal children selected from the community. This study aimed to identify relationships between family psychopathology and adolescents' lifetime history of suicidal states. Family discord, suicide attempts of mother, and substance abuse of mothers and fathers were significantly more prevalent among adolescents with lifetime history of a suicide attempt. Mothers' and fathers' substance abuse was associated with adolescents' lifetime history of suicidal ideation. Results highlight importance of evaluating and treating family psychopathology to reduce risk for youth suicidal states.

Adolescent↗

PubMed1998

P300 latency in geriatric depression.

OBJECTIVE: The purpose of this study was to determine if P300 latency is prolonged in geriatric depression and if longer P300 latency and deficits in initiation and errors of perseveration in depressed elderly patients are related to risk factors for vascular disease. METHOD: Geriatric patients with unipolar depression (N = 43) and elderly comparison subjects (N = 24) were assessed for depressive symptoms, cognitive functions, risk factors for vascular disease, and P300 latency. RESULTS: Depressed elderly patients had longer P300 latency than normal elderly subjects. In the depressed patients, P300 latency was related to deficits in initiation and errors in perseveration. Risk factors for vascular disease were associated not only with P300 latency but also with deficits in initiation and errors in perseveration. CONCLUSIONS: Functional impairment of the cortico-striato-pallido-thalamo-cortical pathways from vascular disease, implicated in late-life depressive disorders, may explain not only deficits in initiation and errors in perseveration but also longer P300 latency in depressed elderly patients. These results are preliminary and need further examination with brain imaging and more sensitive neuropsychological measures.

Aged↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

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↗