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Biomedical subjects

H Hamakawa

Publications and source records attributed to H Hamakawa.

At least 55 records · Page 3Linked to original sources
PubMed1998

Histological effects and predictive biomarkers of TPP induction chemotherapy for oral carcinoma.

The effects of an induction chemotherapy with THP-adriamycin, cisplatin, and peplomycin (TPP) were studied in 32 patients with operable oral cancer. The histological evaluation according to the Shimozato-Oboshi classification was Grade (G) IV in ten cases (31.3%), GIII in one case, and GIIb in four cases. Induction of apoptosis and differentiation-inducing effects, hyperkeratinization or bone formation, were observed in some cases. The overall clinical response rate and histological response rate were 63% and 47%, respectively. Grade III was obtained in seven metastatic lymph nodes of three patients. The expressions of PCNA, p53, and AgNORs before and after chemotherapy were studied. The prechemotherapeutic PCNA positive cell index (PI) of the highly responsive tumors (GIII, IV) was significantly lower than that of the poorly responsive tumors (G0-IIb) (P < 0.01). Similar results were obtained in the evaluation of p53 PI (P < 0.05), suggesting that PCNA and p53 are useful biomarkers for predicting the efficacy of TPP chemotherapy.

Antibiotics, Antineoplastic↗
PubMed1998

Inhibitory effect of a marine microalgal polysaccharide on the telomerase activity in K562 cells.

An extracellular polysaccharide from marine microalga, dinoflagellate Gymnodinium sp. A3 (GA3), showed cytotoxicity to human myeloid leukemia K562 cells. We measured telomerase activity in K562 cells cultured with GA3 polysaccharide. 10.0 micrograms/ml of GA3 polysaccharide inhibited the telomerase activity in the cells completely. Also, we found a decrease in expression of the catalytic subunit of protein phosphatase (PP) type 1, PP1 gamma 1, in K562 cells cultured with GA3 polysaccharide.

Animals↗
PubMed1998

Decrease of nuclear protein phosphatase 1 activity and induction of mitotic arrest and apoptosis by a marine microalgal polysaccharide in human myeloid leukemia U937 cells.

An extracellular polysaccharide, which we designate GA3P, produced from a marine microalga dinoflagellate Gymnodinium sp. A3, has been previously reported to induce apoptosis in lymphoid and myeloid cell lines. We found that the GA3P accumulates cells into the mitotic phase of the cell cycle and decreases nuclear protein phosphatase 1 (PP1) activity in a dose-dependent manner in myeloid leukemia U937 cells. Dose-dependent patterns in the decrease of nuclear PP1 activity and in the accumulation of cells into mitotic phase or apoptotic status by the GA3P were concordant with each other, indicating that the decrease of nuclear PP1 activity at least mediates some of the etiological steps in development of mitotic arrest and apoptosis induced by the GA3P. In addition, the GA3P repressed the expression of protein levels of the PP1 catalytic subunit isoform PP1 gamma 1 gamma 1. We thus suggest that the decrease of nuclear PP1 activity is due to down-regulation of the protein levels of the PP1 gamma 1.

Animals↗
PubMed1998

Increased polyploidy, delayed mitosis and reduced protein phosphatase-1 activity associated with excess copper in the Long Evans Cinnamon rat.

Until now, it is not known whether copper hepatotoxicity impairs mitosis. Enlarged hepatocytes with huge nuclei considered as polyploids are frequently observed in the Long Evans Cinnamon (LEC) rat which exhibits an abnormal accumulation of hepatic copper due to a defect in the gene homologous to human Wilson's disease gene responsible for intracellular copper delivery. This defect may lead to a abnormal mitotic progression in increased polyploidization and is associated with excessive hepatic copper. This study was designed to examine whether excess copper impairs mitotic progression and results in increased polyploidization using a model of LEC rat liver. Polyploidy was analyzed by flow cytometry. The rate of mitotic progression was investigated using the fraction of mitotic hepatocytes or a mitosis-specific phosphoprotein retained in regeneration. Nuclear protein phosphatase-1 (PP-1) activity essential to mitotic progression was measured. The effect of excess copper on incidence of polyploidy, the rate of mitotic progression and nuclear PP-1 activity was investigated using age- or copper overload-dependent changes in them in LEC rat, or genetic profile-dependent changes of them in backcrosses. LEC rat liver showed an increase of polyploidy, a delay of mitotic progression, and a reduction of nuclear PP-1 activity. These abnormal features concurred with increase of copper concentration accompanied by changes of age in LEC rats from 2 to 4 months of age, induced by dietary copper overload in LEC rat, or caused by single genetic defect in backcrosses. Excess copper impairs mitotic progression, resulting in increased polyploidization. Nuclear PP-1 activity is likely to be at least one of targets of copper hepatotoxicity leading to impairment of mitotic progression.

Age Factors↗
PubMed1998

Extraction of cytokeratin from the human submandibular gland and its electrophoretic analysis.

We evaluated a method for extracting cytokeratin (CK) from the normal human submandibular gland and analyzed CK distribution by one- and two-dimensional electrophoresis. Four submandibular glands without histological changes under a light microscope were used as specimens. Intermediate filamentous protein was extracted by a prior modified method CK was not adequately extracted in 1-2% sodium dodecyl sulfate -5% 2-mercaptoethanol solution. On the other hand, 11 bands with molecular weights of 40-58 K were obtained after extraction in 9.5 M urea -5% 2-mercaptoethanol solution. Although fragmentation of cytoskeletal protein was observed, there were no differences in bands according to the strength of homogenization. This fragmentation seemed to be due to restriction degradation by protease. Immunoblotting revealed the reaction of this CK extract to 2 pan-CK antibodies, i.e., K8.13, which recognizes type II basic CK, and C-11, which recognizes CK4, CK5, CK6, CK8, CK10, CK13, CK18. Among monospecific antibodies, anti-CK7 (LDS-68), CK8 (M20), CK13 (KS-1A3), CK18 (CY-90), and CK19 (BA17) antibodies showed positive reactions. Glial fibrillary acidic protein, neurofilament (NF) 68 K, NF160 K, or NF200 K showed no reactions. These results of one- and two-dimensional electrophoretic analysis suggest the presence of CK5, CK7, CK8, CK13, CK14, CK15, CK17, CK18, and CK19 in the normal submandibular gland.

Antibodies, Monoclonal↗
PubMed1997

Multiple regression analysis of relationship between frontal lobe phosphorus metabolism and clinical symptoms in patients with schizophrenia.

We investigated the differences among diagnostic types of 36 schizophrenic patients in the brain phosphorus metabolism in the frontal lobe. We performed phosphorus-31 magnetic resonance spectroscopy (31P-MRS) in the frontal region in patients with schizophrenia of the catatonic (n = 4), disorganized (n = 8), paranoid (n = 10) and undifferentiated (n = 14) types. In the disorganized type, the PME level was significantly decreased compared to those in the other three types, while the phosphodiester (PDE) level tended to be higher, although not significantly, than those in the other types. Using multiple regression analysis, we investigated whether or not the clinical symptoms were correlated with the brain phosphorus metabolism. An increased motor retardation factor score was significantly correlated with decreased PME level, whereas more severe emotional withdrawal and blunted affect were associated with increased PDE level. These results suggest that altered membrane phospholipid metabolism in the frontal region may be associated with negative symptoms and that schizophrenia of the disorganized type is associated with more severe negative symptoms and may present more severe brain abnormalities compared to the other types.

Adolescent↗
PubMed1997

"Chain-link" combined tissue transfer for the reconstruction of the mandible.

We describe a procedure for "chain-link" combined tissue transfer connecting the vascular pedicle of a deep circumflex iliac flap with that of a forearm flap after wide resection of the mandible. Combination of these flaps facilitated the reconstruction of the defect in both intra- and extraoral soft tissue and the mandibular bone. This method is useful when cervical recipient blood vessels are limited due to the wide resection of the primary tumor and radical neck dissection.

Aged↗
PubMed1996

Proton magnetic resonance spectroscopy of the basal ganglia in patients with schizophrenia: a preliminary report.

To examine metabolic changes in the left basal ganglia in chronic schizophrenia, we performed proton magnetic resonance spectroscopy (1H-MRS) in 21 medicated schizophrenic patients and 21 gender and age-matched normal controls. Compared to the normal subjects, the schizophrenic patients showed a significantly increased level of choline containing compounds (Cho) (t = 2.60, p < 0.05) and ratio of Cho to N-acetylaspartate (NAA) (t = 2.46, p < 0.05) in the left basal ganglia. No significant correlation was observed between the 1H-MRS measurements in the left basal ganglia and clinical symptom scores as evaluated using the Brief Psychiatric Rating Scale (BPRS). The chlorpromazine equivalent neuroleptic dosage was positively correlated with the level of NAA (r = 0.38, p < 0.05) and negatively correlated with the Cho/NAA ratio (r = -0.34, p < 0.05). These findings suggest that these changes in metabolites in the left basal ganglia may reflect some of the functional and morphological abnormalities reported previously for the brain in schizophrenia.

Adolescent↗
PubMed1996

High-energy phosphate metabolism in the frontal lobes of patients with panic disorder detected by phase-encoded 31P-MRS.

Using phosphorus-31 magnetic resonance spectroscopy (31P-MRS), we analyzed the brain phosphorous metabolism in 18 patients with panic disorder (PD) and in 18 sex-, age-, and handedness-matched normal controls (NC). All patients were receiving ongoing drug treatments for PD. The evaluation of phosphorous metabolism in the whole frontal lobes revealed no significant differences between the patients and controls in 31P metabolite levels, although the PD patients showed slightly decreased inorganic phosphate (Pi) concentration of the frontal lobes. Moreover, we found a significant asymmetry (left > right) of phosphocreatine (PCr) concentration in the frontal lobes in the patients with PD, suggesting that abnormalities of phosphorous metabolism are present in the frontal lobes of PD patients. Two patients in whom a limited panic episode occurred during measurements showed frontal lobe intracellular pH higher than that in the other patients and that in the NC, suggesting respiratory gaseous alkalosis due to hyperventilation in the anxiety state. 31P-MRS has potential for application in the assessment of brain abnormalities and anxiety state, such as that accompanied by hyperventilation, in PD patients.

Adolescent↗
PubMed1996

Prevalence of cavum septum pellucidum detected by MRI in patients with bipolar disorder, major depression and schizophrenia.

The incidence of cavum septum pellucidum (CSP), which has been widely regarded as a developmental anomaly of little clinical importance in neuropathology, was examined in 113 patients with affective disorders (69 with bipolar disorder and 44 with major depression), 40 schizophrenic patients, and 92 control subjects by magnetic resonance imaging (MRI). Significantly higher incidence of Grade 3-4 CSP (moderate to large) compared with the controls was found only in the schizophrenics. When a broader interpretation of CSP, including indeterminant (Grade 1) and small (Grade 2) CSP was used, three additional patients with bipolar disorder were found to have Grade 1-2 CSP, and the total prevalence of Grade 1-4 CSP in the patients with bipolar disorder was significantly higher than that in the control subjects but slightly lower than that in the schizophrenic patients. CSP was not observed in any patient with major depression. There were no differences between the patients with and without CSP in age, sex, education, or the duration of illness. These findings are consistent with the hypothesis that neurodevelopmental abnormality may be present in schizophrenia, and such an abnormality may also be present in some patients with bipolar disorder.

Adult↗
PubMed1996

Effect of photic stimulation on energy metabolism in the human brain measured by 31P-MR spectroscopy.

Effect of photic stimulation (PS) on energy metabolism in the human occipital cortex was examined by using phosphorus-31 magnetic resonance spectroscopy in 9 normal subjects. Phosphocreatine (PCr)/total phosphorus signal peak area ratio significantly decreased from 12.3% to 10.9% during the 12 minutes of PS (P < 0.05). PCr once returned to a normal level after PS (11.9%) but significantly decreased again 12-18 minutes after PS (10.8%; P < 0.05). Intracellular pH increased from 7.08 to 7.16 during PS, although this increase was not significant. These results suggest that functional alteration of energy metabolism in the brain is different from that in muscles.

Adult↗
PubMed1996

Choline-containing compounds detected by proton magnetic resonance spectroscopy in the basal ganglia in bipolar disorder.

Choline-containing compounds (Cho) were examined by proton magnetic resonance spectroscopy (1H-MRS) in the left subcortical region, including basal ganglia, in 19 euthymic patients with bipolar disorder and 19 age-matched normal controls. Ten of the patients were treated with lithium; the remaining 9 were not treated with lithium for at least 30 d. The Cho to creatine + phosphocreatine (Cr) peak ratio in the bipolar patients (0.75 +/- 0.38 [mean +/- SD]) was higher than that in the normal controls (0.52 +/- 0.26, P < 0.05). There was no significant difference in the Cho:Cr peak ratio between patients treated with lithium (0.63 +/- 0.36) and without lithium (0.89 +/- 0.35). These results do not support the hypothesis that lithium increases the brain choline-containing compounds, but rather imply that membrane breakdown may occur in the basal ganglia of patients with bipolar disorder.

Adult↗
PubMed1995

Lateralized abnormality of high-energy phosphate and bilateral reduction of phosphomonoester measured by phosphorus-31 magnetic resonance spectroscopy of the frontal lobes in schizophrenia.

Magnetic resonance spectroscopy (one-dimensional chemical shift imaging) was used to measure membrane phospholipid metabolism and high-energy phosphate metabolism in the left and right frontal lobes of 27 schizophrenic patients. In the schizophrenic patients, the phosphomonoester peak area was decreased in bilateral frontal lobes compared with that in age-matched normal subjects. On the other hand, the peak area of beta-adenosine triphosphate was increased in the left frontal lobe in the schizophrenic group. The phosphocreatine peak area was increased in the left frontal lobe of schizophrenic patients with high scores on the Scale for the Assessment of Negative Symptoms (SANS).

Adenosine Triphosphate↗
PubMed1995

Lateralized abnormality of high energy phosphate metabolism in the frontal lobes of patients with bipolar disorder detected by phase-encoded 31P-MRS.

High energy phosphate metabolites were measured using phase-encoded in vivo phosphorus-31 magnetic resonance spectroscopy (31P-MRS) in both the left and right frontal lobes of 25 patients with bipolar disorder. Eleven patients were examined in the depressive state, 12 in the manic state, and 21 in the euthymic state. Twenty-one age-matched normal volunteers were also examined. The phosphocreatine (PCr) peak area percentage in the left frontal lobe in the patients in the depressive state was decreased compared with that in the normal controls. It was significantly negatively correlated with the Hamilton Rating Scale for Depression score evaluated at the time of 31P-MRS examination. The PCr peak area percentage in the right frontal lobe in the patients in the manic and the euthymic states was decreased compared with that in the controls. These results are compatible with previous reports describing reduction of glucose metabolism in the left frontal lobe in depressive patients with bipolar disorder and trait-dependent right hemisphere dysfunction in bipolar disorder.

Arousal↗
PubMed1994

Reduction of brain phosphocreatine in bipolar II disorder detected by phosphorus-31 magnetic resonance spectroscopy.

Brain phosphorus metabolism was measured by 31P-MRS in 15 patients with bipolar II disorder (BP II) and 14 patients with bipolar I disorder (BP I). Phosphocreatine (PCr)levels were significantly lower in patients with BP II in all three psychiatric states compared to 59 normal controls (PCr (%) was 13.5 +/- 1.5 (mean +/- SD) for controls, and 12.2 +/- 1.7, 12.1 +/- 1.3, 12.0 +/- 1.9 for hypomanic, euthymic and depressed bipolar II patients respectively). High values of phosphomonoester (PME) were found in BP II patients in the hypomanic and depressive states, but PME values in the euthymic state did not differ significantly from controls. Intracellular pH of BP II patients in all three psychiatric phases was similar to control values, whereas euthymic BP I patients had lower pH values. These results suggest that brain high energy phosphate metabolism may be impaired in BP II and that there may be pathophysiological differences between BP I and BP II.

Adenosine Triphosphate↗
PubMed1994

Phosphorus-31 magnetic resonance spectroscopy and ventricular enlargement in bipolar disorder.

Phosphorus-31 magnetic resonance spectroscopy (31P-MRS) was used to examine whether reduced levels of phosphomonoesters (PME) were correlated with ventricular enlargement in 40 patients with bipolar disorder and 60 age-matched normal control subjects. Ventricular enlargement was assessed by magnetic resonance imaging (1H-MRI) using the following three methods: Evans ratio (ER), Huckman number (HN), and minimum distance of caudate nuclei (MDCN). Although MDCN and ER were significantly larger in the patient group, no significant correlations were found between 31P-MRS and 1H-MRI. PME was negatively correlated with age in bipolar disorder. Decreased levels of PME were found only in bipolar I disorder. Intracellular pH was positively correlated with duration of lithium treatment. These results suggest that the observed PME reduction was not related to ventricular enlargement, but the issue should be further studied with volumetric MRI analysis.

Adult↗