Biomedical subjects

H Kuwabara

Publications and source records attributed to H Kuwabara.

At least 73 records · Page 4Linked to original sources

PubMed1995

Regional striatal DOPA transport and decarboxylase activity in Parkinson's disease.

METHODS: We measured blood-brain barrier transport and decarboxylation of 6-[18F]fluoro-L-DOPA (FDOPA) using PET in patients with Parkinson's disease (n = 7, 57 +/- 7 yr) and age-matched control subjects (n = 7, 60 +/- 6 yr). To visually present regional changes of FDOPA uptake in Parkinson's disease, we introduced maps of FDOPA uptake relative to occipital cortex, averaged across control subjects and Parkinson's disease patients in an MRI-based stereotaxic coordinate space. RESULTS: There was no significant changes in the blood-to-brain transport of FDOPA (KD1) in Parkinson's disease. The KD1 values of the head of caudate were lower than those of putamen in both normal subjects and Parkinson's disease patients. In Parkinson's disease, the activity of L-DOPA decarboxylase (DDC) was differentially reduced in subdivisions of striatum. The residual DDC activity was 63% of the control value in the head of caudate nucleus, 54% in the anterior putamen and 39% in the posterior putamen. The DDC activity in frontal and occipital cortices remained unchanged by the disease. Subtraction of averaged FDOPA uptake maps (control minus Parkinson's disease) visualized a spatial pattern of pathological changes in FDOPA uptake common to Parkinson's disease patients. CONCLUSION: The striatal blood-to-brain transport of FDOPA remained unchanged while the DDC activity was differentially reduced within the striatum in Parkinson's disease. We found the FDOPA uptake maps useful in identifying altered patterns of FDOPA metabolism common in Parkinson's disease.

Biological Transport↗

PubMed1994

Elevated dopa decarboxylase activity in living brain of patients with psychosis.

The hypofrontality theory of the pathogenesis of schizophrenia predicts that cortical lesions cause psychosis. During a search for abnormalities of catecholaminergic neurotransmission in patients with complex partial seizures of the mesial temporal lobe, we discovered an increase of the rate of metabolism of an exogenous dopa tracer (6-[18F]fluoro-L-dopa) in the neostriatum of a subgroup of patients with a history of psychosis. When specifically assayed for this abnormality, patients with schizophrenia revealed the same significant increase of the rate of metabolism in the striatum. The finding is consistent with the theory that a state of psychosis arises when episodic dopamine excess is superimposed on a trait of basic dopamine deficiency in the striatum. The finding is explained by the hypothesis that cortical insufficiency, a proposed pathogenetic mechanism of both disorders, causes an up-regulation of the enzymes responsible for dopa turnover in the neostriatum as well as the receptors mediating dopaminergic neurotransmission.

Adult↗

PubMed1994

Malignant fibrous histiocytoma of the larynx.

Malignant fibrous histiocytoma of the upper respiratory tract is rare. We report a case of a glottic malignant fibrous histiocytoma in a 46-year-old man. Ultrastructural findings demonstrated that tumor cells were composed of fibroblast-like cells with abundant rough endoplasmic reticulum, histiocyte-like cells with numerous lysosomes and transitional cells with characteristics of both the fibroblast-like and histiocyte-like cells. Laryngeal microsurgery was performed as surgery and the patient has done well without recurrence to date (8 months after surgery).

Endoplasmic Reticulum↗

PubMed1994

A correlation of argyrophilic nucleolar organizer regions with prognoses in patients with maxillary sinus squamous cell carcinoma.

Argyrophilic nucleolar organizer regions (AgNORs) were determined by a semiautomatic image analyzer in a group of 28 patients with T2 or T3 maxillary sinus squamous cell carcinoma. The group was separated into recurrent and non-recurrent groups, metastatic and non-metastatic groups, as well as groups strongly or weakly positive for epidermal growth factor receptor (EGFR). The mean number and area of AgNOR dots per nucleus and the mean size of each dot were calculated. The mean number and area were significantly greater than those in normal cells (P < 0.001), but not in recurrent and non-recurrent groups, metastatic and non-metastatic groups and groups separated by EGFR. There was also no difference found in the mean sizes of tumor and normal cells. These results suggest that AgNOR is related to malignant transformation, but not prognosis.

Aged↗

PubMed1994

Pigmented squamous cell carcinoma of the alveolar ridge in the oral mucosa.

The clinical and morphologic features of a pigmented squamous cell carcinoma of the alveolar ridge in an 81-year-old Japanese woman are reported. The tumor was typical, well-differentiated squamous cell carcinoma but had many melanin-containing cells within it. Electron microscopy showed melanosomes in macrophages, melanocytes, and neoplastic squamous cells. Those in the neoplastic squamous cells seemed to have been excreted from the cytoplasmic processes of melanocytes.

Aged↗

PubMed1994

A kinetic analysis of 6-[18F]fluoro-L-dihydroxyphenylalanine metabolism in the rat.

A previous study of the metabolism of 6-[18F]-fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) in rats pretreated with carbidopa contained information amenable to kinetic analysis. Using these data, tracer transfer coefficients and metabolic rate constants were estimated. After intravenous injection, FDOPA in circulation was O-methylated (k0D = 0.055 min-1), and the metabolite (O-methyl-FDOPA) escaped from plasma with a rate constant (k-1M) of 0.01 min-1. The initial clearance of FDOPA to striatum (K1D) was 0.07 ml g-1 min-1, and the equilibrium distribution volume (VeD) was 0.67 ml g-1. The initial clearance of O-methyl-FDOPA to striatum (K1M) was 0.08 ml g-1 min-1, and the equilibrium distribution volume (VeM) was 0.75 ml g-1. The rate constant of FDOPA decarboxylation (k3D) was 0.17 min-1 in striatum. The elimination of 6-[18F]fluorodopamine (FDA) from striatum suggested an apparent rate constant for monoamine oxidase activity (k7') of 0.055 min-1. 6-[18F]Fluorohomovanillic acid (FHVA) was formed from 6-[18F]fluoro-L-3,4-dihydroxyphenylacetic acid with a rate constant (k11) of 0.083 min-1, and FHVA was eliminated from striatum (k9) with a rate constant of 0.12 min-1. The steady-state concentration ratios of FDA and its metabolites were shown to be functions of these rate constants.

Animals↗

PubMed1994

[Evaluation of the method of treating non-Hodgkin's lymphoma].

Forty-two patients with non-Hodgkin's lymphoma were treated between October 1983 and December 1992 in the department of Otolaryngology, Kagawa Medical School Hospital. The twenty-six of these patients whose tumor originated in Waldeyer's ring and who were diagnosed as Stage I or II have been reviewed. In principle, method of treatment was a combination of chemotherapy and radiotherapy. Between 1983 to 1987, COP was primarily used (9 cases) as combination chemotherapy, and after 1988 CHOP was used (17 cases). VAMA was used to treat the poor response and recurring cases. The five-year estimated overall survival rates calculated by the Kaplan-Meier method were 33.3% and 94.1% in the COP and CHOP groups, respectively. We investigated age, stage, cell type and grade, as factors related to recovery, but except for cell type, there were no significant differences in overall survival. The most serious side effect was decreased leucocyte count, but we prescribed G-CSF and were able to continue treatment.

Adult↗

PubMed1994

[Immunohistological study of dendritic cells and macrophages in sino-nasal lesions--distributions in metaplastic squamous epithelium and squamous cell carcinoma].

Dendritic cells, macrophages and lymphocytes infiltrating the epithelia of sino-nasal lesions were investigated immunohistochemically using antibody S-100 protein for dendritic cells, Ki-M1P for macrophages, MT1 for T-cells and L26 for B-cells, respectively. Seventy-five specimens of sino-nasal mucosae involving 51 cases of metaplastic squamous epithelium (MSE), 12 of inverted papilloma, 1 of atypical hyperplasia and 11 of squamous cell carcinoma (SCC) were studied. Dendritic cells were observed in 12 cases of MSE (23.5%), in 4 of inverted papilloma (33.3%), and in 6 of SCC (54.5%). More dendritic cells were found infiltrating MSE of the infective and fibrotic types than of the mild and edematous types, histopathologically. Furthermore, infiltration correlated with the degree of squamous differentiation in MSE, but not in SCC. The number of macrophages was significantly smaller in MSE than in columnar ciliated epithelium, while that in SCC was significantly greater than that in MSE. With dendritic cell infiltration macrophages in MSE as well as SCC and T-cells in and around the carcinoma were often increased. These findings suggest that dendritic cells may be attracted to maturative squamous epithelium, and may play an important role in the immunologic defence mechanisms of MSE. Dendritic cells, in contrast, may play a role in the cellular immune response of T-cells against the carcinoma.

Adolescent↗

PubMed1993

CD7, CD34-positive stem cell leukemia arising in agnogenic myeloid metaplasia.

Agnogenic myeloid metaplasia (AMM) is a chronic myeloproliferative disorder arising from a single hematopoietic cell. Approximately 5% of reported cases of AMM have terminated in leukemic crisis; however, the precise characteristics of the leukemic cells have rarely been reported. We report a case of AMM that occurred in a 42-year-old man and was complicated by leukemic transformation. The leukemic cells were morphologically lymphoblastoid cells with a negative reaction to peroxidase staining, and phenotypically characterized as CD7+, CD34+, HLA-DR+, CD4-, CD8-, CD10-, CD13-, and CD33-. Southern blot analysis revealed that T cell receptor-beta, gamma, and immunoglobulin heavy chain genes in leukemic cells were retained in germ-line configuration. These observations suggest that leukemic cells in our case involved early hematopoietic stem cells rather than those strictly committed to myeloid or lymphoid precursors. To our knowledge, this is the first report of stem cell leukemia arising in a patient with AMM.

Acute Disease↗

PubMed1993

Administration of the new COMT inhibitor OR-611 increases striatal uptake of fluorodopa.

L-Dopa is metabolized to 3-O-methyldopa (3OMD) by catechol-O-methyltransferase (COMT). This reduces the amount of L-dopa available for entry into brain. We studied the effect of OR-611, a new COMT inhibitor, on plasma and brain 6-[18F]-fluoro-L-dopa (6FD) metabolism in cynomolgus monkeys with positron emission tomography (PET). OR-611 pretreatment substantially reduced plasma 6FD metabolism to 3-O-methylfluorodopa (3OMFD). PET measurements of striatal 6FD concentrations showed an average 2.3-fold increase following OR-611 pretreatment, compared to the same animals in the control state. OR-611 inhibits plasma metabolism of 6FD and increases brain uptake of this L-dopa analog. OR-611 appears to be a promising agent as an adjunct to L-dopa for the treatment of patients with Parkinson's disease.

Animals↗

PubMed1993

Absent recruitment of capillaries in brain tissue recovering from stroke.

The density of perfused capillaries (dCAP), defined as capillaries that transport glucose, as well as the volume fraction of these capillaries in the vascular bed (fCAP), and the mean transit time of blood through the capillaries (tCAP), were calculated from hemodynamic variables obtained in vivo by positron tomography of brains of six patients affected by stroke. Each patient was studied twice, within 38 hrs of the insult, and one week later. 38 ischemic and 38 contralateral mirror regions were compared. The metabolic rate for glucose (CMRglc) was determined on the basis of regional calculations of the lumped constant. No significant change of the lumped constant was observed in any region. In normal regions, no significant differences of any variables existed between the first and second studies. In the infarct regions of the first study, CMRglc and CMRO2 (cerebral metabolic rate for oxygen) were 30-50% of control (deactivation) and CBF (cerebral blood flow), capillary density, and the capillary diffusion capacity for fluorodeoxyglucose (K1) were similarly reduced, although the oxygen/glucose ratio was only 3.75 in the ischemic regions. While fCAP decreased, tCAP doubled. One week after the first study, blood flow returned to normal in the infarct regions despite continued depression of metabolism. Capillary density and diffusion capacity remained low, indicating absent recruitment of nutrition vessels (perfusion capillaries).

Adult↗

PubMed1993

Prognostic significance of epidermal growth factor receptor in squamous cell carcinoma of the maxillary sinus.

The expression of epidermal growth factor receptor (EGFR) was determined immunohistochemically in two groups of maxillary sinus squamous cell carcinomas, one with recurrences at the primary site after combination therapy with radiotherapy, chemotherapy and/or surgery and one without local recurrences. Using a four-graded scale (-, +, + +, + + +), 9 of the 10 recurrent carcinomas had a staining intensity and proportion of stained cells of + + or more. A comparable staining intensity was found in 9 of the 18 non-recurrent carcinomas. This difference is statistically significant (Fisher's exact probability test, P < 0.05). These results indicate that an increased expression of EGFR may influence the recurrence rate of squamous cell carcinoma of the maxillary sinus after combined therapy.

Aged↗

PubMed1993

Human striatal L-dopa decarboxylase activity estimated in vivo using 6-[18F]fluoro-dopa and positron emission tomography: error analysis and application to normal subjects.

DOPA decarboxylase is the enzyme directly responsible for the synthesis of the neurotransmitters dopamine and serotonin, and indirectly of noradrenaline, in brain. We used the decarboxylation coefficient (k3D) of 6-[18F]fluoro-DOPA (FDOPA) to denote the relative activity of L-DOPA decarboxylase in vivo in the human brain. To determine the relative enzyme activity with positron emission tomography (PET), we evaluated the model that separates the metabolism into compartments of nondiffusible and diffusible (i.e., transient) tracer metabolites. Error analysis indicated that the least-squares optimization alone was not sufficient to yield accurate estimates of k3D in the presence of the inherent error of PET. To improve the accuracy of the k3D estimates by optimizing the number of parameters, we introduced biological constraints which included a tracer partition volume (Ve) common to frontal cortex and striatum, and a fixed ratio (q) between the blood-brain barrier transport coefficients of O-methyl-[18F]fluoro-DOPA and FDOPA, the two sources of radioactivity in plasma. We found that a two-step analysis yielded sufficiently accurate estimates of k3D. The two steps include the initial estimation of the partition volume in frontal cortex and the subsequent use of this value to determine k3D in striatum and other structures. We studied twelve healthy controls (age 45 +/- 15 years). The average k3D value was 0.081 +/- 0.024 min-1 (coefficient of variation (COV) 30%) for caudate nucleus, 0.074 +/- 0.013 min-1 (COV 18%) for putamen, and 0.010 +/- 0.005 min-1 (COV 50%) for cerebral cortex.

Adult↗

PubMed1993

6-[18F]fluoro-L-dopa metabolism in living human brain: a comparison of six analytical methods.

In 11 normal volunteers and six patients with Parkinson's disease, we compared six different analyses of dopaminergic function with L-3,4-dihydroxy-6-[18F]fluorophenylalanine (FDOPA) and positron emission tomography (PET). The caudate nucleus, putamen, and several reference regions were identified in PET images, using magnetic resonance imaging (MRI). The six analyses included two direct determinations of DOPA decarboxylase activity (k3D, k3*), the slope-intercept plot based on plasma concentration (K), two slope-intercept plots based on tissue content (k3r, k3s), and the striato-occipital ratio [R(T)]. For all analyses, the difference between two groups of subjects (normal volunteers and patients with Parkinson's disease) was larger in the putamen than in the caudate. For the caudate nucleus, the DOPA decarboxylase activity (k3D, k3*), tissue slope-intercept plots (kr3, ks3); and striato-occipital ratio [R(T)] analyses significantly discriminated between the normal volunteers and the patients with Parkinson's disease (p < 0.005) [with least significance for k3* (p < 0.05)], while the plasma slope-intercept plot (K) failed to do so. For the putamen, the values for k3D, k3*, K, k3r, k3s, and R(T) of normal volunteers were significantly higher than those of patients (p < 0.005) [with least significance for K (p < 0.025)]. Linear correlations were significant between k3D and k3s; k3D and k3r; k3D and R(T); and k3D and k3*, in this order of significance. We found no correlation between k3D and K values in the caudate nucleus.

Adult↗

PubMed1993

Pharmacokinetics of plasma 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine ([18F]Fdopa) in humans.

Like native DOPA, [18F]-6-fluoro-L-3,4-dihydroxyphenylalanine ([18F]FDOPA) is subject to methylation and decarboxylation. To determine the rates of formation and elimination of [18F]FDOPA metabolites, plasma from human subjects undergoing positron emission tomographic (PET) studies was analyzed by high-performance liquid chromatography (HPLC). In addition to the principal metabolite O-methyl-[18F]FDOPA (OMe[18F]FDOPA), two decarboxylated metabolites were detected in plasma from carbidopa pretreated subjects. The concentrations of each metabolite during 90 min following tracer injection could be described as a function of the concentration of [18F]FDOPA, and two rate constants; k0, the rate of formation, and k-1, the rate of clearance. Plasma metabolite time series generated from total plasma activity curves and measured rate constants were in close agreement with the actual concentrations determined by HPLC fractionation. Population means for k0 (0.011 +/- 0.002 min-1) and k-1 (0.010 +/- 0.003 min-1) were used to generate "simulated" plasma curves. The measured and generated plasma curves were used as inputs for estimation of partition and decarboxylation coefficients of [18F]FDOPA in brain. The use of generated input functions from normal population means of transfer coefficients did not introduce a systematic error into the estimate of the enzyme activity. However, the high variability of these estimates in patients precludes the use of this technique as an alterative to individual HPLC measurements.

Adult↗

PubMed1993

Striatal L-dopa decarboxylase activity in Parkinson's disease in vivo: implications for the regulation of dopamine synthesis.

L-DOPA is a large neutral amino acid subject to transport out of, as well as into, brain tissue. Competition between dopamine synthesis and L-DOPA egress from striatum must favor L-DOPA egress if decarboxylation declines relatively more than transport in Parkinson's disease. To test this hypothesis, we injected patients with Parkinson's disease with a radiolabeled analogue of L-DOPA and recorded regional brain radioactivity as a function of time by means of positron emission tomography. We simultaneously estimated the activity of the decarboxylating enzyme and the amino acid transport. In the striatum of patients, we found the L-DOPA decarboxylase activity to be reduced in the head of the caudate nucleus and the putamen. However, the rate of egress of the DOPA analogue was unaffected by the disease and thus inhibited dopamine synthesis more than predicted in the absence of L-DOPA egress.

Corpus Striatum↗

PubMed1993

Human T lymphotropic virus type I associated myelopathy with pulmonary and cutaneous lesions.

A necropsy case of human T lymphotropic virus I (HTLV-I) associated myelopathy (HAM) in a 64 year old man with serological and genetical confirmation of HTLV-I infection is reported. The spinal cord, lung, and skin were mainly affected. Severe degeneration had occurred in the spinal cord, not only in the lateral columns but also in the anterior and posterior columns. The degenerate lesions showed proliferation of capillaries, loss of myelin and axon, and perivascular and parenchymal infiltration with T lymphocytes and foamy macrophages in the white matter. T lymphocytes had infiltrated the lung and there was vascular proliferation in the peribronchus. OPD4 positive cells predominated in the lung. The patient also had erythrodermia where dense and bandlike HTLV-I infected lymphoid cell infiltration was observed, with mild atypia and epidermotropism. HTLV-I may cause multiorganic inflammatory disorders, although the definitive role of HTLV-I in the pathogenesis is still unknown.

Bronchial Diseases↗

PubMed1993

Enhanced incorporation of 1-beta-D-arabinofuranosylcytosine by pretreatment with etoposide.

We examined the effects of timing of administration of etoposide on cytosine arabinoside (ara-C) incorporation into DNA in L1210 ascites tumor. At 1 hr after injection of ara-C, 3-hr and 6-hr pretreatments with 15 mg/kg of etoposide increased ara-C incorporation to more than 200% as compared to that of ara-C given alone. Simultaneous administration of etoposide, however, decreased ara-C incorporation to 33% of that of ara-C alone. These results might explain the previously reported sequence dependency of the antitumor effect of etoposide and ara-C.

Animals↗