Biomedical subjects

R Kubota

Publications and source records attributed to R Kubota.

At least 91 records · Page 5Linked to original sources

PubMed1992

Dose-responsive effect of radiotherapy on the tumor uptake of L-[methyl-11C]methionine; feasibility for monitoring recurrence of tumor.

The L-[methyl-11C]methionine [( 11C]Met) uptake by rat AH109A tumor was decreased irradiation-dose dependently from the control to 5, 10 and 20 Gy. After 10 Gy irradiation, the [11C]Met uptake decreased earlier than the tumor volume reduction, and later, it significantly increased earlier than the recurrent growth. Double tracer autoradiography with [14C]Met and 4-[18F]fluoroantipyrine showed a decrease in the [14C]Met tumor uptake without change of blood flow after irradiation. The [11C]Met uptake representing amino acid metabolism is a sensitive indicator for monitoring radiotherapeutic effect on tumor.

Animals↗

PubMed1992

Active melanogenesis in non-S phase melanocytes in B16 melanomas in vivo investigated by double-tracer microautoradiography with 18F-fluorodopa and 3H-thymidine.

3,4-Dihydroxy-2-[18F]fluoro-L-phenylalanine (2-[18F]FDOPA) and [6-3H]thymidine ([3H]Thd) were simultaneously injected into mice transplanted with B16 melanomas of FM3A mammary carcinoma. Melanogenesis was differentiated from DNA synthesis in the mitotic cell cycle by monitoring grain distribution with double-tracer microautoradiography. The percentages of pigmented cells were inversely proportional to those of [3H]Thd-labelled cells, indicating that the greater the number of melanocytes, the smaller was the number of proliferating cells. The number of grains produced by 2-[18F]FDOPA in the [3H]Thd-unlabelled melanocytes was significantly higher (P < 0.001) than the numbers in the [3H]Thd-labelled melanocytes and in nonmelanocytes. The [3H]Thd-unlabelled non-melanocytes and FM3A cells showed the lowest accumulation of 2-[18F]DOPA, which may have resulted from the basic amino acid demand by malignant neoplasms via amino acid transport. The [3H]Thd-labelled cells, regardless of whether they were pigmented or not, had slightly more grains with 2-[18F]FDOPA than the [3H]Thd-unlabelled non-melanocytes (P < 0.05), which may have resulted from the enhanced amino acid requirement for proliferation. Melanogenesis appeared to be activated only in the non-S phase of the mitotic cycle in melanocytes.

Animals↗

PubMed1992

Efficiency of grain production and latent image fading in F-18 micro-autoradiography.

In 18F micro-autoradiography using a frozen section method, the grain production was measured relative to the exposure time and radioactivity. The grain production increased until 6-hr exposure, but 7-hr or longer exposure induced a characteristic of latent image fading. However, the ratios of the efficiency of grain production between two different 18F-radioactivities (11.9 and 2.3 mBq/100 microns2) were constant over experimental exposure times, thus indicating that quantitative analysis by grain counting is preserved.

Animals↗

PubMed1992

Tumor radiotherapy monitoring with radioscintigraphy tracers: a comparative study with multiple-tracer technique.

A comparative multiple-tracer study was performed to assess the tracer feasibility of monitoring tumor radiotherapy. Metabolic tracers for glucose, amino acid, nucleic acid metabolism: F-18-FDG, C-14-Met, H-3-Thd, and F-18-FdUrd and conventional Ga-67 were compared in the same AH109A radiotherapy model using a new quadruple-tracer technique. F-18-FDG showed a large uptake change and a steady response to radiotherapy which is similar to Ga-67. F-18-FdUrd showed a rapid decrease, but the range of change in uptake was narrow. H-3-Thd and C-14-Met showed a rapid response to irradiation and a high sensitivity for monitoring radiotherapy, suggesting that if labeled with C-11, they may be feasible for PET study.

Animals↗

PubMed1992

[Therapeutic effect of lymphocytapheresis on patients with HTLV-I-associated myelopathy (HAM)].

Lymphocytapheresis (LCP) was performed in 7 patients (1 male and 6 females) with HAM to delete lymphocytes from their peripheral blood, resulting in an improvement of motor disability in 6 of 7 patients with HAM. The therapeutic effect appeared within one day after first LCP, and reached maximum in 2 or 3 sessions of LCP. The side effects were only dysesthesia in 5 patients during LCP and mild leukopenia in a patient after LCP. Both of them were mild and transient. The effect of LCP continued for two to five months in 6 patients, the remaining one deteriorated in a month. In the study of T cell subsets of peripheral blood lymphocytes by flowcytometry, the CD4/8 ratio and the cell counts of CD4+ DR+, CD8+ DR+ and IL-2R positive cells were gradually decreased by LCP. These results suggest that LCP is one of the effective therapies for HAM and peripheral blood lymphocytes implicate in the pathogenesis of HAM.

Adult↗

PubMed1992

[Cerebrotendinous xanthomatosis--a case of brain MRI abnormality and osteoporosis].

A 37-year-old male with cerebrotendinous xanthomatosis showed brain abnormal MRI findings and osteoporosis. His parents had no similar symptoms. He had mental retardation since childhood. Swelling of Achilles tendons was noticed at age 28, and gait disturbance appeared at age 34. Physical examination revealed bilateral cataracts and swelling of Achilles tendons. Neurologically, he showed mental retardation, cerebellar ataxia and spastic tetraparesis. Cerebrotendinous xanthomatosis was diagnosed by marked elevations of serum cholestanol level (24.3 micrograms/ml) and cholestanol/cholesterol ratio (1.81%) as well as characteristic clinical manifestations. On brain MRI study, T2-weighted sequence showed bilateral focal lesions with high intensity signal in the globus pallidus and cerebellar white matter adjacent to the dentate nucleus, and T1-weighted sequence showed low to iso-intensity signal in the same regions. These findings suggested demyelination rather than xanthoma or lipid infiltration. Radiological examination showed mild osteoporosis of lumbar bone. However, serum levels of vitamin D3 and calcitonin were within normal range, and renal function was normal. Osteoporosis in this patient possibly resulted from disuse bone atrophy for several years. The combination therapy of oral administration of chenodeoxycholic acid and HMG-CoA reductase inhibitor (pravastatin), and LDL apheresis slightly improved EEG abnormality and gait disturbance, but not brain MRI abnormality.

Adult↗

PubMed1992

[Peripheral blood IgA bearing cells in children with Henoch-Schönlein purpura nephritis and IgA nephropathy. Relationship between IgA bearing cells and clinico-pathological findings or T alpha 4 cells].

It has been reported that patients with Henoch-Schönlein purpura nephritis (HSPN) and IgA nephropathy (IgAN) showed an familial increase of IgA bearing peripheral blood lymphocyte. To elucidate the relationship between IgA bearing cells and clinico-pathological findings or T cell subsets, especially IgA specific helper T cells (T alpha 4 cells), 20 patients with HSPN and 33 patients with IgAN were studied. The results demonstrated as follows; 1) IgA bearing cells were significantly increased in patients with both HSPN and IgAN (p < 0.001). 2) The increase of IgA bearing cells was well correlated to the degree of patients' proteinuria and hematuria (p < 0.05), and also correlated with the severity of patients' renal pathological findings in both diseases. 3) With relation to the T cell subsets in patients with both diseases, only the CD4+ Leu8- cells (helper T cells) and T alpha 4 cells were significantly increased, in addition, positive correlation between IgA bearing cells and CD4+ Leu8- cells or T alpha 4 cells was observed. 4) The increase of IgA bearing cells seemed to be transient in HSPN, but remained elevated in IgAN. In conclusion, it was indicated that patients with HSPN and IgAN could have IgA related immunological abnormalities, which may be reflected in the increase of IgA bearing cells and T alpha 4 cells. It was also suggested that determination of IgA bearing cells could be a useful parameter which may be reflected in the disease activity of HSPN and IgAN.

Adolescent↗

PubMed1992

Intratumoral distribution of fluorine-18-fluorodeoxyglucose in vivo: high accumulation in macrophages and granulation tissues studied by microautoradiography.

While 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is a useful tumor imaging agent, its intratumoral distribution has not been described well at the cellular level. In order to demonstrate cellular localization of [18F]FDG and 2-deoxy-D-[3H]glucose (3H-DG) uptake by the tumor in vivo, C3H/He mice transplanted subcutaneously with FM3A tumors were studied 1 hr after intravenous injection of [18F]FDG or 3H-DG using micro- and macro-autoradiography. Fluorine-18-FDG and 3H-DG showed the same distribution pattern in the tumor with both autoradiographic methods. The newly formed granulation tissue around the tumor and macrophages, which were massively infiltrating the marginal areas surrounding necrotic area of the tumor showed a higher uptake of [18F]FDG than the viable tumor cells. A maximum of 29% of the glucose utilization was derived from nontumor tissue in this tumor. The comparison of double-tracer autoradiographic distribution patterns of [18F]FDG and [6-3H]-thymidine showed the differences and the similarities between glucose utilization and the DNA synthesis. Whole proliferating tissue metabolizes [18F] FDG but not vice versa. High accumulation of [18F]FDG in the tumor is believed to represent high metabolic activity of the viable tumor cells. Our results showed that one should consider not only the tumor cells proper but also the non-neoplastic cellular elements, which appear in association with growth or necrosis of the tumor cells, for precise analysis of [18F]FDG uptake in tumor-bearing subjects, especially after anti-neoplastic treatment.

Animals↗

PubMed1992

[Enhancement of the effects of anticancer agents on B16 melanoma cells by combination with cepharanthine--I. Alkaloids].

The anticancer effect of a podophyllotoxin derivative, etoposide (ETOP), and the vinca alkaloids, vincristine (VCR) and vindesine (VDS), on the colony forming efficiency (CFE) of B16 melanoma cells, and the CFE inhibition by the combination with a biscoclaurine alkaloid, Cepharanthine (Ceph) were studied in vitro. By combination with Ceph, CFE was reduced about 44% for ETOP, 31% for VCR and 30% for VDS compared to CFE without Ceph. Therefore, the effect of each anticancer agent was enhanced by combination with Ceph, especially that of Ceph and ETOP. The combination effect was greater when the low concentration of the agents was used. From the present study, the combination of ETOP and Ceph appears to be the more effective form of treatment.

Alkaloids↗

PubMed1992

[Enhancement of the effects of anticancer agents on B16 melanoma cells by combination with cepharanthine--II. Antimetabolite, alkylating agent, nitrosourea].

We have studied chemotherapy enhancement by the combination of the biscoclaurine alkaloid, Cepharanthine (Ceph), using the inhibition of colony forming efficiency (CFE) of B16 melanoma cells in vitro. Hydroxyurea, antimetabolite, showed a time-dependent inhibition of CFE, and the combination with Ceph enhanced CFE inhibition by 29%, which is stable and independent of the treatment time. Dacarbazine, a biological alkylating agent, given with Ceph showed a time-dependent inhibition of CFE (43%). MCNU, a nitrosourea, with Ceph showed the greatest inhibition of CFE (67%) among the anticancer agents used. The CFE inhibition was time-dependent and required a higher concentration of MCNU. In this series of studies using CFE inhibition of B16 melanoma cells in vitro, etoposide showed the best effect by the combination with Ceph, which seems to be a candidate for in vivo evaluation.

Alkaloids↗

PubMed1992

[Autoradiographic demonstration of 18F-FDG distribution within mouse FM3A tumor tissue in vivo].

To demonstrate the distribution of 2-deoxy-2-18F-fluoro-D-glucose (FDG) within the tumor in vivo, C3H/He mice transplanted with FM3A tumors were studied one hour after intravenous injection of FDG using whole-body, macro- and micro-autoradiography. The whole-body autoradiograph showed that the tumor mass as well as the brain, heart, bone marrows, and the diaphragm and crus diaphragm were clearly visualized. The macro-autoradiograph showed the heterogeneous distribution of FDG in the tumor mass. Markedly dense areas surrounding the tumor and the necrotic area were observed. Micro-autoradiograph showed the high grain densities in the macrophages between the necrosis and viable tumor cells, and in the young granulation tissues demarcating between the tumor and surrounding intact host tissues. Our results showed that the FDG uptake in the tumors may reflect not only the uptake by the tumor cells but also that by the inflammatory reaction elements.

Animals↗

PubMed1991

Possibility for tumor detection with fatty acid analogs.

Newly synthesized 17-[18F]fluoro-3-methylheptadecanoic acid ([18F]BMHDA), 16-[18F]fluoropalmitic acid ([18F]PA) and 15-(p-[125I]iodophenyl)-3-R,S-methylpentadecanoic acid ([125I]BMIPP), fatty acid tracers, were examined for the possibility of tumor imaging using 10 tumor models in rats and mice. The highest tumor/muscle ratios with [18F]BMHDA were 2.3 using rat tumor AH109A and 1.9 using mouse tumor B16F1 (tumor accumulation 0.41 +/- 0.05, 4.29 +/- 0.77% ID/g, respectively). Tumor/muscle ratios with [125I]BMIPP and [18F]PA were lower than those with [18F]BMHDA. Labeled fatty acids seem to have a lower potential for tumor detection.

Animals↗

PubMed1991

Epidemiology of progressive muscular dystrophy in Okinawa, Japan. Classification with molecular biological techniques.

We studied the prevalence of various types of progressive muscular dystrophy (PMD) in Okinawa, Japan on December 31, 1989 and the incidence of Duchenne muscular dystrophy (DMD) in 5-year periods from 1957 to 1985. We classified patients with PMD clinically, electrophysiologically, molecular biologically and immunohistochemically with antidystrophin antibody, especially for sporadic cases of DMD, Becker muscular dystrophy (BMD) and limb-girdle muscular dystrophy (LG). The prevalence for all PMD in Okinawa was 7.13 X 10(-5) for DMD, 1.82 X 10(-5) for BMD in the male population, 1.55 X 10(-5) for LG, 1.14 X 10(-5) for congenital muscular dystrophy, 2.03 X 10(-5) for facioscapulohumeral muscular dystrophy (FSH), and 9.13 X 10(-5) for myotonic dystrophy (MD) in the total population. The incidence of DMD in the period 1957-1985 was 15.41 X 10(-5) live-born males (LBM) and 3.21 X 10(-5) LBM for BMD. The incidence has apparently declined in Okinawa since 1975. The prevalence of BMD, FSH and MD was rather high in Okinawa compared with previous reports. Molecular biological techniques for classifying patients were indispensable for the epidemiological study of PMD.

Cross-Cultural Comparison↗

PubMed1991

[A case of rigid spine syndrome associated with severe respiratory failure].

Rigid spine syndrome (RSS) is clinically characterized by progressive limitation of flexion of the spine and contractures of other joints. We herein report a 27-year-old man with RSS, who underwent tracheotomy because of severe restrictive respiratory failure. He had limitation of neck flexion and proximal muscle weakness from early childhood and was diagnosed as having muscular dystrophy at 16 years old. He was suffered from dyspnea and his first tracheotomy was performed at 24 years old. Two years later, the second tracheotomy was done because his respiratory failure was aggravated. He had limitation of spine flexion, scoliosis, but no limited range of elbow and wrist joints movement except mild contracture of ankle joints. Serum CK level was elevated to 590 IU/L. Repeated ECG examinations showed negative T wave but no conduction block. In his family, his parents and brother had neither similar clinical symptoms nor heart block. Chest X-ray study showed elevated diaphragm and enlarged heart shadow (CTR = 65%). Percent VC and FEV1 in sitting position were 14.6% and 100%, respectively. Arterial blood gas analysis showed PaO2 of 34.2 mmHg and PaCO2 of 77.2 mmHg. The density of paraspinal muscle in CT scan was severely decreased. Needle EMG showed myogenic change. Muscle biopsy from left biceps brachii showed myopathic change with mild type 2 fiber grouping. After the second tracheotomy, he was on a respiratory during sleep but mostly off in the daytime. His clinical features are different from Emery-Dreifuss muscular dystrophy because he had no heart conduction block and no family history, but progressive respiratory failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Tracer feasibility for monitoring tumor radiotherapy: a quadruple tracer study with fluorine-18-fluorodeoxyglucose or fluorine-18-fluorodeoxyuridine, L-[methyl-14C]methionine, [6-3H]thymidine, and gallium-67.

In a rat AH109A tumor model, metabolic tracers for glucose, amino acid, and nucleic acid metabolisms (2-deoxy-2-[18F]fluoro-D-glucose (18FDG), L-[methyl-14C]methionine (14C-Met), [6-3H]thymidine (3H-Thd), and 2'-deoxy-5-[18F]fluorouridine (18FdUrd], and the conventional radionuclide 67Ga-citrate were used to assess the feasibility of monitoring tumor radiotherapy using a quadruple tracer technique. Two combinations of four tracers (18FDG or 18FdUrd, 14C-Met, 3H-Thd and 67Ga) were compared in a time-course study after single-dose irradiation (20 Gy) and were also used in a dose-dependency study performed 6 days after 5, 10, 15, or 20 Gy of irradiation. Fluorine-18-FDG showed a large change in uptake and a steady response to radiotherapy. Fluorodeoxyuridine showed a rapid decrease after radiotherapy, but the range of change in uptake was narrow. Gallium-67 could not detect tumor response early after treatment, but showed a marked change in uptake later. [6-3H]Thd and 14C-Met showed a rapid response to irradiation and a high sensitivity for monitoring radiotherapy, suggesting that they may be feasible for PET studies.

Animals↗

PubMed1991

Selective 2-[18F]fluorodopa uptake for melanogenesis in murine metastatic melanomas.

The relationship between 3,4-dihydroxy-2-[18F]fluoro-L-phenylalanine (2-[18F]FDOPA) uptake and melanogenesis was studied using mice bearing two B16 melanomas: B16-F1 has a higher melanin synthesis ability and a slower growing rate than the higher metastatic B16-F10. A significantly higher 2-[18F]FDOPA uptake by B16-F1 than by B16-F10 and a reverse relationship for the uptake of [14C] 2-deoxy-2-fluoro-D-glucose and [3H]thymidine were observed 1 hr postinjection. F1-to-F10 ratios of both the 2-[18F]FDOPA uptake and the acid-insoluble radioactivity increased to about 5 at 6 hr, which paralleled the melanin content. FM3A mammary carcinoma showed a 2-[18F]FDOPA uptake similar to the B16-F10 but without the acid-insoluble radioactivity. With D,L-DOPA loading, a 55% decreased uptake by FM3A 1 hr postinjection was significantly greater than the 20% reduction in both melanomas. O-Methylated 2-[18F]FDOPA was a predominant acid-soluble metabolite in all tumors. Whole-body autoradiography discriminated the two melanomas clearly. 2-[18F]FDOPA may be a promising tracer for the selective imaging of melanogenesis.

Animals↗

PubMed1991

[Nationwide survey of necrotizing myelopathy associated with malignancy in Japan].

Twenty-two cases of transverse myelopathy associated with malignancy were collected in nationwide survey in Japan. Paraneoplastic necrotizing myelopathy (PNM) was suspected in 9 of them and 8 cases were diagnosed as radiation myelopathy (RM), clinically and pathologically. Other 5 cases had different causes of transverse myelopathy. In comparison with PNM and RM, malignant lymphoma, flaccid paraplegia and sphincter dysfunction were highly associated in the patients with PNM. On the other hand, lung cancer, spastic paraplegia, abnormality in spinal MRI and dysesthesia in legs as an initial symptom were prevalent in the cases of RM. Six cases of them were compared pathologically. Although all cases had no metastasis of malignant cells, five cases of PMN showed acute and chronic necrosis and rarefaction of spinal cord with or without perivascular cuffing. One case of RM had focal spinal cord atrophy and no lymphocytes infiltration. Immunohistochemically, herpes simplex virus type 2 (HSV2) infection in spinal cord was shown in the 2 cases of the necrotizing myelopathy. Virus infection such as HSV2 could be one of causes of PNM and virological study must be done in the cases of necrotizing myelopathy associated with malignancy.

Adult↗

PubMed1990

Localization of [18F]fluorodeoxyglucose in mouse brain neurons with micro-autoradiography.

This is the first study of micro-autoradiography (micro-ARG) for [18F]2-fluoro-2-deoxy-D-glucose [( 18F]FDG). The localization of [18F]FDG was demonstrated in dendrites of neuron and also in the myelinated axon in mouse normal brain in vivo. The nucleolus was relatively free of label. The counted silver grain numbers in autoradiogram were linearly correlated to the 18F radioactivities in the specimen. The micro-ARG using positron emitting 18F is a very time-saving technique with 4 hours exposure compared with the conventional method using 3H- or 14C-labeled tracers.

Animals↗