Biomedical subjects
Publications and source records attributed to H Kuwabara.
A secretory carcinoma of the breast, associated with axillary node metastasis, unilateral gynaecomastia, and chronic active hepatitis, occurred in a 66 year old man. Although secretory carcinoma of the breast usually occurs in children and adult women, our case shows that it can rarely occur in the elderly male.
The authors analyzed the histological effect of preoperative chemotherapy for 41 colorectal advanced cancer patients using resected specimens. Twenty patients in the UFT + LV group received 400 mg/day of UFT and 30 mg/day of leucovorin for 10-14 days just before the operations. Twenty-one patients with UFT alone received UFT 400 mg/day during the same period. Only one patient in the UFT + LV group developed the side effect of mild leukocytopenia. The histological effect of the UFT + LV group was superior to that of the UFT alone group (p = 0.03). The number of Grade 1a and 1b in the UFT + LV group was 14 (60.9%) and 7 (30.4%), while in the UFT group 16 (66.7%) and 2 (8.3%). Histological examination revealed no lesions which showed Grade 2 and 3 in both groups. There was the tendency for the histological effect in moderately differentiated adenocarcinomas to be superior to that in well-differentiated adenocarcinomas in both group. The histological effect in metastatic lymph nodes was superior to that in the original colorectal lesions in both groups. This suggests preoperative chemotherapy with UFT + LV and UFT could achieve the clinical down-staging of advanced colorectal cancer.
UNLABELLED: Nonuniform distributions of lung perfusion scintiscans obtained by SPECT were quantified to supplement qualitative lung scintiscans. A total of 126 lung perfusion scintigraphy examinations were performed between February and December 1996 on a subject population of 102 patients, including 8 control subjects. All of the subjects were broadly classified according to whether they had pulmonary disease or nonpulmonary disease. The latter group was subdivided into a group with cardiac disease and other diseases. The grade of breathlessness was classified according to whether oxygen inhalation was required, the clinical severity of the breathlessness and patient's performance status. Blood gas analysis was performed in 21 cases, and pulmonary function testing was performed in 26 cases. METHODS: With the subjects resting in the supine position, 185 MBq 99mTc-macroaggregate albumin was infused. From reconstructed SPECT images, the volume of lung as a whole calculated at 10% of threshold was assumed to be the functional lung volume, and the functional volume rates were calculated in 10% threshold widths from 10% to 100% of thresholds. Assuming the total absolute difference in functional volume rate between each subject and the control to be the distribution index of the lung as a whole (D index), we quantified the degree of nonuniform distribution in each subject. RESULTS: The D index of all subjects ranged from 2.7 to 72.2. The mean D index in pulmonary disease was significantly higher than in nonpulmonary disease (p < 0.0005) and cardiac disease (p < 0.005). It was significantly positively correlated with the grade of breathlessness, significantly negatively correlated with the oxygenation index and significantly positively correlated with measured vital capacity and forced expiratory volume in 1 sec as percentages of their predicted values. CONCLUSION: The D index is a useful indicator for quantifying nonuniform distributions on lung scintiscans. If it is used as a supplement to qualitative interpretation of scintiscans, pulmonary perfusion scintigraphy will become a more useful technique for clinical evaluation of treatment and assessment of breathlessness and respiratory failure than the usual one.
The kinetic behaviour of [3H]DOPA in living rat brain was investigated by compartmental modelling of measured activities from combined metabolite pools in a time-series (180 min) of static autoradiograms from right cerebral hemispheres. Two models of [3H]DOPA uptake and metabolism that incorporated the removal of the decarboxylation product, [3H]dopamine, from brain were significantly more accurate than a model in which [3H]dopamine accumulated irreversibly in situ. Present estimates of [3H]DOPA kinetic constants were compared to previously published results based on the analysis of measured activities from individual metabolite pools separated by chromatographic fractionation of [3H]DOPA metabolites in the left cerebral hemispheres of the same rats. Autoradiographic estimates of DOPA decarboxylase activity with respect to [3H]DOPA in brain (k3DOPA) were under-estimated several-fold relative to chromatographic estimates; this discrepancy is explained by post-mortem enzyme activity and omission of biological compartments from the models. However, autoradiographic estimates of the unidirectional blood-brain clearance of [3H]DOPA (K1DOPA) and monoamine oxidase activity with respect to [3H]dopamine in brain (k7DA') agreed with chromatographic estimates. This concordance represents the first empirical validation of compartmental modelling of autoradiographic data as a method for quantitatively investigating the kinetic behaviour of radiolabelled L-DOPA in living mammalian brain.
A novel GM-CSF-dependent myeloid cell line, OHN-GM, was established from a patient who developed acute myelogenous leukaemia (AML) as a consequence of myelodysplastic syndrome (MDS). As the patient had previously received cytotoxic chemotherapy for Hodgkin's disease, the MDS and AML were probably related to such therapy. Sequential karyotypic analysis established a del(5q) as the initial cytogenetic abnormality. Additional alterations, including t(10;13)(q24;q14), had developed subsequently during disease progression. Southern blot analysis of OHN-GM cells suggested deletion of one allele of the IRF-1 gene, although no aberrant transcripts were detected. Fluorescence in situ hybridization analysis revealed the deletion of the Rb gene due to the t(10;13)(q24;q14) translocation, and Western blot analysis demonstrated the absence of Rb protein in OHN-GM cells. Finally, the OHN-GM cells exhibited two missense point mutations in highly conserved regions of the p53 gene. These observations suggest that a multistep process, involving alterations of Rb and p53 genes, may have contributed to the patient's disease development and progression. To our knowledge, OHN-GM is the first cell line derived from a therapy-related AML. These cells may aid the investigation of leukaemogenesis as well as the biology of secondary leukaemia.
OBJECTIVE: To investigate the expression of sialosyl-Tn antigen (STn) in human benign and malignant prostate. MATERIALS AND METHODS: The expression of STn was investigated immunohistochemically in formalin-fixed and paraffin-embedded tissue specimens from 56 patients with primary prostatic adenocarcinoma (median age 74.3 years, range 47-89) and 20 patients with benign prostatic hyperplasia (median age 73.4 years, range 60-87). RESULTS: STn was expressed in only three (4%) of the 20 hyperplastic glands and the benign areas adjacent to the 54 carcinomas; by contrast, STn was expressed in 34 (61%) of the 56 carcinomas. The frequency of STn positivity was much higher in well-differentiated carcinomas than in those poorly differentiated. CONCLUSION: STn is expressed with malignant transformation of the prostatic epithelial cells and immunohistochemical methods using commercially available STn monoclonal antibody may be useful as an adjunct for distinguishing carcinoma from benign tissue.
When used to measure blood flow, water leaves a residue in the vascular bed, which may contribute to the calculation of increased blood flow during functional activation of brain tissue. To assess the magnitude of this contribution with the two-compartment positron emission tomography (PET) method, we mapped the water clearance (K1) of the brain as an index of cerebral blood flow (CBF) and the apparent vascular distribution of nonextracted H2 15O (Vo). The latter map represented mainly the cerebral arterial and arteriolar volume. We also prepared subtraction maps (delta K1, delta Vo) of the response to vibrotactile stimulation of the fingertips of the right hand of six normal volunteers. Using magnetic resonance (MR) images of all subjects, the data were rendered into Talairach's stereotaxic coordinates and the averaged subtraction images (activation minus baseline) merged with the corresponding averaged MRI image. The delta K1 map revealed the expected response in the primary sensory hand area; the delta Vo response was located about 13 mm more anteriorly, close to the central fissure, most likely reflecting changes of the arteries feeding the primary sensory hand area. We conclude that cerebral perfusion and cerebrovascular responses to vibrotactile stimulation may occur in disparate locations that can be identified separately by using the two-compartment method.
To test the hypothesis that dopamine (DA) receptors influence cerebral DOPA-decarboxylase (DDC) activity in vivo, we used HPLC to measure the kinetics of the cerebral uptake and metabolism of [3H]DOPA in carbidopa-treated rats, and in rats also treated acutely with a DA receptor antagonist (flupenthixol, 2 mg/kg, intraperitoneally) or a DA receptor agonist (apomorphine, 200 microg/g, subcutaneously). The unidirectional blood-brain clearance of [3H]DOPA (K1DOPA, 0.030 mL g(-1) min(-1)) increased by 50% after flupenthixol. The magnitudes of the relative DDC activity (k3DOPA) in striatum (0.20 min(-1)), olfactory tubercle (0.11 min(-1)), and hypothalamus (0.15 min(-1)) of carbidopa-treated rats were doubled with flupenthixol, but cortical DDC activity was unaffected (0.02 min(-1)). Apomorphine reduced the magnitude of k3DOPA in striatum by 20%. The rate constant for catabolism of [3H]DA formed in brain (k7', monoamine oxidase [MAO] activity), which ranged from 0.025 min(-1) in striatum to 0.08 min(-1) in hypothalamus of carbidopa-treated rats, globally increased 2- to 4-fold after flupenthixol, and decreased to 0.003 min(-1) in striatum after apomorphine. These in vivo results confirm the claim that acute blockade of DA receptors with flupenthixol stimulates the synthesis of [3H]DA from [3H]DOPA, and that this [3H]DA is subject to accelerated catabolism. Conversely, activation of the DA receptors with apomorphine inhibits DDC activity and DA catabolism.
Malignant myoepithelioma (myoepithelial carcinoma) of the breast is extremely rare. A case is reported of a 46 year old female with clear cell mammary malignant myoepithelioma that, on histological examination, was glycogen abundant clear cell carcinoma. Immunohistochemically, the clear cells showed myoepithelial differentiation--that is, they were a smooth muscle actin and S100 protein positive. This case shows that glycogen abundant clear cell carcinoma is a variant of malignant myoepithelioma of the breast.
A 28-year-old male patient with both IgA nephropathy and an unusual case of Fabry's disease has been followed for 10 years. Diagnosis of both these diseases was made by histological examination of renal biopsy tissues and the enzyme activities of alpha-galactosidase A. Serial biopsies revealed the hithertofore unrecognized process of glomerular glycolipid accumulation peculiar to Fabry's disease at the initial stages of the disease. Physical examinations and routine laboratory analyses failed to show significant signs of Fabry's disease throughout the 10-year period. While alpha-galactosidase A activity is markedly decreased in the plasma of this patient as in classical Fabry hemizygotes, the activity in leukocytes and culture fibroblasts showed a considerable residual activity. Fabry's disease associated with IgA nephropathy apparently is extremely rare, and the present subclinical case is unique in that the early stages of substrate accumulation are demonstrable.
Primary malignant melanomas of the lacrimal sac are extremely rare. In this report, the histologic findings of primary malignant melanoma of the lacrimal sac with surrounding melanosis are presented. Histologically, the surrounding melanosis showed radial proliferation of atypical melanocytes along the mucosal epithelium. Although we came to no firm conclusion as to whether the malignant melanoma in the present case was preceded by melanosis (radial proliferation of atypical melanocytes), to our knowledge this is the first description of lacrimal sac malignant melanoma associated with a lesion of this kind in the surrounding epithelium.
It is uncertain if acute lymphoblastic leukemia (ALL) cells expressing myeloid makers can respond to granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage colony-stimulating factor (GM-CSF). We investigated the effects of G-CSF (0.01 microgram/ml) and GM-CSF (0.01 microgram/ml) on [3H]thymidine (TdR) uptake, and the cytotoxicity of 1-beta-D-arabinofuranosylcytosine (ara-C) in leukemia cells from 17 pediatric patients. ALL cells without myeloid markers did not respond to G-CSF or GM-CSF. On the other hand, these cytokines enhanced the [3H]TdR uptake and cell growth, not only of AML cells but also of ALL cells expressing myeloid antigens. However, G-CSF and GM-CSF did not always enhance the growth inhibitory effect of the cell cycle specific drug ara-C when the cells were co-cultured with the drug. There was no relationship between cell growth and the amount of [3H]TdR incorporation or the intracellular ara-CTP level. These results indicate the heterogeneous effects of G-CSF and GM-CSF on cell growth and ara-C sensitivity in childhood leukemia cells.
We investigated the effects on leukocyte adhesion to cultured human dermal microvascular endothelial (DMvE) cell by antibody mediated ligation of platelet/endothelial cell adhesion molecule-1 (PECAM-1) on neutrophils. Preincubation of neutrophils with anti-PECAM-1 antibody markedly enhanced their adhesion to DMvE cells, while the adhesion-increasing action was cancelled out by anti-CR3 or anti-LFA-1 beta (CD18) antibody. These findings suggest that ligation of PECAM-1 on neutrophils increases their adhesion to cultured DMvE cells depending on the beta 2 integrin family, and PECAM-1 may have a crucial role in dermal inflammation.
We discuss a 45-year-old man who presented with ileus due to multiple submucosal tumors of the small and large intestines. Emergency operation was performed and histological examination of the tumors revealed pleomorphic cells with helper/inducer T-cell phenotype. Polymerase chain reaction (PCR) analysis using DNA extracted from the paraffin-embedded material showed that the intestinal, jejunal and femoral lymphoma samples contained human T-cell leukemia virus type-I (HTLV-I) DNA. Although no atypical lymphocytes were found in the peripheral blood, a diagnosis of adult T-cell leukemia was made. The PCR analysis of HTLV-I infection using paraffin-embedded materials seems to be useful when we encountered patients with T-cell lymphoma in the gastrointestinal tract.
6-[18F]fluoro-L-DOPA (FDOPA) has been used as a tracer for the cerebral activity of L-3,4-dihydroxyphenylalanine (DOPA)-decarboxylase in studies of positron emission tomography (PET). However, the substitution of fluorine on the aromatic ring may alter the disposition and metabolism of FDOPA from that of endogenous DOPA. In the present study, the kinetics of the peripheral metabolism and the facilitated unidirectional blood-brain clearance of [3H]DOPA and FDOPA were compared in Wistar rats pretreated with carbidopa. In arterial plasma, FDOPA was O-methylated with an apparent rate constant (0.031 min-1) 3-fold that of [3H]DOPA in the same rats. The O-methylated metabolite of FDOPA (OMe-FDOPA) was eliminated from plasma at a rate constant (0.018 min-1) 3-fold that of OMe-[3H]DOPA. The mean unidirectional blood-brain clearance of FDOPA (4.5 mL.hg-1.min-1) in six brain regions was 60% higher than that of [3H]DOPA.
The expressions of the three catalytic subunits of protein phosphatase (PP) type 1 and 2A, PP1 alpha, PP1 gamma 1, and PP2AC, were examined in 14 cases of three types of osteogenic tumor using immunohistochemical analysis. The percentage of tumor cells stained positively with antiserum against PP1 catalytic subunit-isoform PP1 gamma 1 was significantly higher in malignant osteogenic tumors than in benign osteogenic tumors. Furthermore, malignant osteogenic tumor showed markedly high S-phase fraction in the cell cycle of tumor cells, as compared to benign osteogenic tumors. These results suggest that PP1 gamma 1 is involved in the accelerated growth of malignant cells in osteogenic tumors.
To test the hypothesis that L-DOPA decarboxylase (DDC) is a regulated enzyme in the synthesis of dopamine (DA), we developed a model of the cerebral uptake and metabolism of [3H]DOPA. The unidirectional blood-brain clearance of [3H]DOPA (K1D) was 0.049 ml g-1 min-1. The relative DDC activity (k3D) was 0.26 min-1 in striatum, 0.04 min-1 in hypothalamus, and 0.02 min-1 in hippocampus. In striatum, 3,4-[3H]dihydroxyphenylacetic acid ([3H]DOPAC) was formed from [3H]DA with a rate constant of 0.013 min-1, [3H]homovanillic acid ([3H]HVA) was formed from [3H]DOPAC at a rate constant of 0.020 min-1, and [3H]HVA was eliminated from brain at a rate constant of 0.037 min-1. Together, these rate constants predicted the ratios of endogenous DOPAC and HVA to DA in rat striatum. Pargyline, an inhibitor of DA catabolism, substantially reduced the contrast between striatum and cortex, in comparison with the contrast seen in autoradiograms of control rats. At 30 min and at 4 h after pargyline, k3D was reduced by 50% in striatum and olfactory tubercle but was unaffected in hypothalamus, indicating that DDC activity is reduced in specific brain regions after monoamine oxidase inhibition. Thus, DDC activity may be a regulated step in the synthesis of DA.
Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease) is a bleeding disorder attributed to a vascular developmental abnormality. It is transmitted as an autosomal dominant trait. A 63-year-old female was admitted because of repeated episodes of severe anemia which resulted from bleeding of telangiectases in the gastric mucosa. Conventional therapies including endoscopical microwave coagulation and ethanol injection were not effective. The persistent anemia necessitated frequent blood transfusion. Estrogen was orally administrated and blood transfusion became unnecessary. Thus, estrogen therapy should be considered as one of the effective treatments for recurrent severe anemia due to hereditary hemorrhagic telangiectasia.