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Biomedical subjects

T Tominaga

Publications and source records attributed to T Tominaga.

At least 55 records · Page 3Linked to original sources

Early rehabilitation effect for traumatic spinal cord injury.

OBJECTIVE: To determine the natural course of traumatic spinal cord injury (SCI) and the effect of early rehabilitation on it. DESIGN: A retrospective, multicenter study. SETTING: Sixteen Rosai hospitals and 1 medical school. PARTICIPANTS: One hundred twenty-three SCI patients (104 men, 19 women; mean age, 48.8 +/- 17.7yr) enrolled. INTERVENTIONS: Dividing the subjects into an early rehabilitation group and a delayed group; differences were ensured by international classification of SCI. MAIN OUTCOME MEASURES: Using the American Spinal Injury Association (ASIA) classifications, the motor recovery rate (MRR) was defined as (ASIA motor score at discharge - ASIA motor score at admission)/(100 - ASIA motor score at admission). The regression lines for FIM instrument score and ASIA motor score were determined for 6 subgroups (early or delayed tetraplegia, central cord injury, paraplegia) by the MRR staging. The regression lines for physical or cognitive FIM score and ASIA motor score were also determined for 6 subgroups. RESULTS: Three stages were obtained: acute stage: 2 weeks postinjury; recovery stage: 2 weeks to 6 months postinjury; and chronic stage: more than 6 months postinjury. Regression lines showed that rehabilitation improved physical functional independence for ASIA motor score, especially in the early rehabilitation subgroups. There was no correlation between cognitive FIM score and ASIA motor score in 6 subgroups. CONCLUSION: Early SCI rehabilitation contributes to good physical activities of daily living for motor function.

Activities of Daily Living↗

Collagen synthesis and collagenase activity of cryopreserved heart valves.

OBJECTIVE: Durability of the valve seems to be dependent on the remodeling ability of the valve itself, which is controlled by both collagen synthesis and collagenolytic activity of valvular fibroblasts and endothelial cells. However, the balance of collagen synthesis and collagenolysis of the cryopreserved valve has not yet been clearly revealed. Thus, we assessed the collagen synthesis and collagenolysis ability of the cryopreserved valve. METHODS: Twelve valves were divided into 2 groups: freshly harvested valves (n = 6) and cryopreserved valves (n = 6). We measured the collagen content using Sirius red, a dye selective to the collagen. Collagen synthesis was evaluated by means of the tritiated proline incorporation method. Noncollagenase-digestible counts, which represent protein synthesis, and collagenase-digestible counts, which represent collagen synthesis, were estimated. Collagenase activity of the valves was assessed by gelatin zymography. RESULTS: The collagen content of the cryopreserved group was maintained. The noncollagenase-digestible counts of the cryopreserved group decreased from 3862 +/- 1180 counts/mg to 1174 +/- 1362 counts/mg, and the collagenase-digestible counts of the cryopreserved group were 831 +/- 762 counts/mg compared with the value of 1062 +/- 136 counts/mg for the freshly harvested group. The collagenase activity of the cryopreserved group was observed at the same level as that of the freshly harvested group, despite the serious endothelial damage of the cryopreserved valves. CONCLUSIONS: Although the collagen synthesis of cryopreserved valves was relatively maintained, the protein synthesis was highly diminished, and the collagenolysis ability was activated immediately after the thawing process. These results imply that the cryopreservation procedure itself may cause the collagen metabolism to be on the degradable side, which will lead to valve failure.

Animals↗

Postoperative chemoendocrine therapy for women with node-positive stage II breast cancer with combined cyclophosphamide, tamoxifen, and 1-hexylcarbamoyl-5-fluorouracil.

OBJECTIVE: To find out whether the addition of 1-hexylcarbamoyl-5-fluorouracil to a postoperative regimen of oral cyclophosphamide and tamoxifen improved the prognosis of carcinoma of the breast. DESIGN: Randomised controlled clinical trial. SETTING: 127 Institutions in Japan. SUBJECTS: 785 Patients with stage II carcinoma (palpable axillary nodes) who had total mastectomy and axillary clearance. INTERVENTIONS: The control group were given oral cyclophosphamide 50 mg/day and tamoxifen 20 mg/day for 2 years; the experimental group were given these drugs plus 1-hexylcarbamoyl-5-fluorouracil 300 mg/day for 2 years. RESULTS: There was no survival advantage (and more toxicity) in the experimental group, except in a subgroup with 1-3 axillary nodes involved. CONCLUSION: The advantage of triple chemotherapy in the subgroup must be substantiated by a new randomised trial confined to patients with 1-3 axillary nodes involved.

Administration, Oral↗

Elevation of serum pro-gastrin-releasing peptide in patients with medullary thyroid carcinoma and small cell lung carcinoma.

Medullary thyroid carcinoma (MTC) arises from parafollicular or C cells of the thyroid gland and produces a variety of peptides such as calcitonin (CT) and gastrin-releasing peptide (GRP). Here we measured serum levels of pro-gastrin-releasing peptide (Pro-GRP), a more stable precursor of GRP, in 15 patients with MTC (4 males, 11 females) who did not show any clinical or radiologic signs of small cell lung cancer. Serum Pro-GRP levels were elevated in 80% (12/15) patients. Significant correlation was observed between serum Pro-GRP and CT (r = 0.52) and carcinoembryonic antigen (CEA) (r = 0.56). Serum Pro-GRP levels also correlated with tumor size (r = 0.70). Serum Pro-GRP levels also decreased below the cut-off range in one patient after surgical resection. Our data suggest that Pro-GRP, which is considered to be a specific marker for small cell lung carcinoma, seems to be also helpful and additional marker for the diagnosis and monitoring the response to therapy in patients with MTC in addition to calcitonin as the main tumor marker.

Adult↗

Correlation between fatty liver and coronary risk factors: a population study of elderly men and women in Nagasaki, Japan.

The relation between fatty liver, detected by ultrasonography as a marker of visceral fat accumulation, and coronary risk factors was studied in 810 elderly men and 1,273 elderly women in Nagasaki, Japan from 1990 to 1992. The prevalence of fatty liver was 3.3% in the male and 3.8% in the female non-obese participants (BMI, body mass index < 26.0 kg/m2) and 21.6% in the male and 18.8% in the female obese participants (26.0 kg/m2 < or = BMI). Fatty liver was significantly (p < 0.01) related to hypercholesterolemia and hypertriglyceridemia in the men and to hypertension, hypercholesterolemia, low-HDL cholesterol, hypertriglyceridemia and diabetes mellitus or impaired glucose tolerance (DM+IGT) in the women independent of age, obesity, smoking and drinking. Non-obesity with fatty liver, rather than obesity with or without fatty liver, had the highest odds ratio for hypertension and low-HDL cholesterol in the men and for hypercholesterolemia, low-HDL cholesterol, hypertriglyceridemia and DM+IGT in the women. The prevalence of fatty liver is the same in elderly men and women, and fatty liver is an independent correlate of coronary risk factors in the elderly.

Aged↗

Pulmonary nocardiosis associated with idiopathic thrombocytopenic purpura.

A 69-year-old woman with idiopathic thrombocytopenic purpura, who was regularly followed and treated with prednisolone and danazol, was admitted to our hospital because of shortness of breath. Chest roentgenogram showed a large amount of left-sided pleural effusion. Gram-positive branching rods, subsequently identified as Nocardia farcinica, were isolated from the fluid. Antibiotic treatment together with pleural drainage with an intercostal catheter resulted in complete remission of pyothorax. Pulmonary nocardiosis is a rare disease, but recognition of the disease in immunocompromised patients and the prompt initiation of appropriate treatments based on isolation of the pathogen can lead to a successful outcome.

Aged↗

Schedule dependency of antitumor activity in combination therapy with capecitabine/5'-deoxy-5-fluorouridine and docetaxel in breast cancer models.

Docetaxel and capecitabine are being prescribed for the treatment of breast cancer. In this study, we tried to identify the optimal administration schedule in combination therapy with these anticancer drugs in human cancer xenograft models. Capecitabine was given p.o. daily for 2 weeks (days 1-14), whereas docetaxel was given i.v. on day 1, day 8, or day 15 in a 3-week regimen to the mice bearing MX-1 human breast cancer xenograft. The combination showed better antitumor efficacy than the monotherapy of either agent in either dosing regimen. However, the most potent and synergistic activity was observed when docetaxel was given on day 8. This potent effect appears to be characteristic of the combination of docetaxel with capecitabine or its intermediate metabolite 5'-deoxy-5-fluorouridine (doxifluridine; 5'-dFUrd). Docetaxel given on day 8 showed a potent effect in combination with 5'-dFUrd, but a much weaker effect was observed in combination with 5-fluorouracil or UFT, a fixed combination of tegafur and uracil. Better efficacy was also observed in the MAXF401 human breast cancer xenograft and in the mouse A755 mammary tumor when docetaxel was given at the middle of the capecitabine or 5'-dFUrd treatment rather than other dosing regimens. In contrast, the efficacy in WiDr human colon cancer xenograft was somewhat better when docetaxel was given on day 1. One possible explanation for the synergy is that docetaxel up-regulates tumor levels of thymidine phosphorylase, the enzyme essential for the activation of capecitabine and 5'-dFUrd to 5-fluorouracil. In fact, docetaxel up-regulated the thymidine phosphorylase levels 4.8- and 1.9-fold in the WiDr and MX-1 models, respectively. However, it did not significantly up-regulate in the MAXF401 and A755 models in which a potent combination effect was observed as well. Other mechanisms, particularly those for the synergy with docetaxel given at the middle during capecitabine/5'-dFUrd administration, would also exist. Based on these observations, clinical studies on the day 8 combination regimen with docetaxel and capecitabine/5'-dFUrd are warranted.

Animals↗

[Developments of hormonal agents for breast cancer].

Endocrine therapy for breast cancer, which began with ovariectomy, has a history of more than 100 years. Tamoxifen has been an epoch-making drug during the late 20th century. Recently LHRH analogues which work as downregulators of estrogen production and many aromatase inhibitors (AI), both non-steroidal and steroidal have been developed in Japan. Fadrozole was the only AI until anastrozole was approved a few months ago. Letrozole was shown to be a better AI than fadrozole by prospective randomized double blind examination; however, it is not licenced yet. The reason is that the appropriate dosage is not identical to that of Western countries. We have reached a time when order-made medicine should take into consideration such differences as race and individuality.

Adult↗

[A phase I study of docetaxel (TXT) and doxifluridine (5'-DFUR) combination therapy in patients with advanced and recurrent breast cancer].

We investigated efficacy and tolerance of chemotherapy with doxifluridine (5'-DFUR) and docetaxel (TXT) in advanced/recurrent breast cancer. Subjects were enrolled by central registration. The regimen included 5'-DFUR orally for 14 consecutive days, and TXT intravenously on day 8. It was repeated every 3 weeks, as long as possible, including dosage levels of 5 scheduled steps. Patient registration was started in August 1999 and 5 patients given level 1 regimen (5'-DFUR, 800 mg/day; TXT, 50 mg/m2) were evaluated. Although the results revealed neutropenia of grade 3 in 4/5 patients and leukocytopenia in 2/5 patients, no other side effects were observed. Taking into consideration the toxicity profiles of each drug in level 1, a level 2b regimen (5'-DFUR, 800 mg/day; TXT, 60 mg/m2) was accepted. Seven patients were registered for level 2b dosage and were examined for the safety of the regimen. Two patients discontinued the level 2b regimen due to percutaneous adverse reactions (DLT) and 6/7 patients developed neutropenia of grade 4. Clinical effects in level 1 group included: 1 CR, 2 PR, 1 long NC (NC longer than 24 weeks), and 1 NE, for a response rate of 60.0% (3/5 patients). Those in level 2b included: 2 CR, 2 PR, 1 NC, and 2 NE, for a response rate of 57.1% (4/7 patients). Based on the safety and efficacy of the combined therapy, the recommended dosage of this regimen is 5'-DFUR, 800 mg/day, combined with TXT, 60 mg/m2. A Phase II study is being conducted using this dosage.

Adult↗

[Distal anterior inferior cerebellar artery aneurysms: report of three cases and literature review].

Aneurysm at the distal portion of the anterior inferior cerebellar artery (AICA) is uncommon and only 55 cases have been documented in the literature. Here we report an additional three cases with review of the literature. All three patients presented with subarachnoid hemorrhage. The ruptured aneurysms were located at the meatal loop of the AICA in all three patients and one patient had another unruptured aneurysm at the lateral branch distal to the meatal loop. Two patients underwent surgical trapping of the aneurysms, and the other patient was treated with endovascular coiling because of poor clinical condition. Increase of hearing disturbance was found in two patients who underwent surgery or endovascular coiling, respectively. Clinical features and treatment of these rare lesions are discussed with reference to the 7th and 8th nerve impairments as preoperative symptoms and postoperative complications.

Adult↗

Cellular biology of cryopreserved allograft valves.

Although analyzing the precise mechanisms of cryopreserved allograft valve failure may be difficult due to a number of crucial reasons and the interrelationships between the overlapping mechanisms, there is some evidence that cryopreservation is currently the best method of storing allograft valves. The present review shows the basic cellular biology of cryopreserved allograft valves for long-term durability, particularly relevant to allograft valve cellular viability, the immune response mainly caused by viable donor cells, and the preservation and regeneration of the intrinsic extracellular matrix. The present findings are as follows. First, cryopreservation produces serious damage to cytosolic and mitochondrial functions of both endothelial cells and fibroblasts, which may cause valve failure after implantation. Second, although the collagen synthesis of cryopreserved valves was relatively maintained, total protein synthesis was highly diminished and the collagenolytic ability was activated immediately after the thawing process. These findings imply that the cryopreservation itself may cause the collagen metabolism to become degradable, which will lead to valve failure. Further examination of collagen metabolism and modulation of the collagenolytic activity will be necessary to improve the tissue preservation for improved clinical use.

Apoptosis↗

[Diffusion-weighted magnetic resonance imaging (MRI) in acute brain stem infarction].

Diffusion-weighted magnetic resonance imaging (DWI) provides one of the earliest demonstrations of ischemic lesions. However, some lesions may be missed in the acute stage due to technical limitation of DWI. We therefore conducted the study to clarify the sensitivity of DWI to acute brain stem infarctions. Twenty-eight patients with the final diagnosis of brain stem infarction(midbrain 2, pons 9, medulla oblongata 17) who had been examined by DWI within 24 hours of onset were retrospectively analyzed for how sensitively the initial DWI demonstrated the final ischemic lesion. Only obvious(distinguishable with DWI alone without referring clinical symptoms and other informations) hyperintensity on DWI was regarded to show an ischemic lesion. Sixteen(57.1%) out of 28 patients had brain stem infarctions demonstrated by initial DWI. In the remaining 12 cases, no obvious ischemic lesion was evident on initial DWI. Subsequent MRI studies obtained 127 hours, on average after the onset showed infarction in the medulla oblongata in 11 cases and in the pons in one case. Negative findings of DWI in the acute stage does not exclude possibility of the brain stem infarction, in particulary medulla oblongata infarction.

Adult↗

Quantification of optical signals with electrophysiological signals in neural activities of Di-4-ANEPPS stained rat hippocampal slices.

We have quantified the optical signals of synaptically induced neural activities in an in vitro brain slice preparation in terms of electrophysiological signals. The qualification was done using electrophysiologically well known neural activities in the CA1 area of rat hippocampal slices stained with externally applied fluorescent voltage-sensitive dye (VSD; Di-4-ANEPPS). Together with a newly designed CCD-based digital high-speed camera system and epi-fluorescent optics, our improvements were made on a protocol for staining using a newly designed chamber system. These improvements enabled us to make stable and reliable recordings of optical signals and electrophysiological measurements without affecting the physiological status and to make a quantitative comparison between them. The time course and amplitude of the optical signal showed fair agreement with intracellular and extracellular recordings, and was stable over 2 h. The optical signal followed synaptically induced long-term potentiation (LTP) as monitored by the electrophysiological signals. A regional difference in the amount of LTP was found in optical signals and was confirmed in the electrophysiological signals. These results demonstrate the capabilities of our improved method as an alternative but more potent tool to measure the neuronal activities of brain slice in addition to electrophysiological method.

Action Potentials↗

Viability of cryopreserved semilunar valves: an evaluation of cytosolic and mitochondrial activities.

BACKGROUND: Despite long-standing, widespread use of cryopreserved allografts, the basic cellular biology of these tissues is still yet unknown. The present investigation was undertaken to study cryopreserved heart valves from the standpoint of cytosolic esterase and mitochondrial dehydrogenase activities. METHODS: Cryopreserved porcine aortic cusps were observed in an unfixed fresh condition with a confocal laser scanning microscope using fluorescent dye. Porcine cusps and cultured human umbilical vein endothelial cells were divided into three groups, including fresh, cold-preserved, and cryopreserved specimens, and cytosolic esterase activity and mitochondrial dehydrogenase activity were analyzed in each. RESULTS: Confocal laser scanning microscope findings disclosed a widely distributed fluorescence in the cusp. Cytosolic esterase activity within human umbilical vein endothelial cells (28%+/-9.0%) after cryopreservation was significantly less than that it was in the cusps (72%+/-21%). Mitochondrial dehydrogenase activity of cryopreserved human umbilical vein endothelial cells and that of cusps fell to 44%+/-6.1% and 64%+/-17% respectively; the difference between the two values was not significant. CONCLUSIONS: Cryopreservation appeared to produce serious damage to cytosolic and mitochondrial functions of endothelial cells. The cytosolic function of cusps, mainly consisting of fibroblasts, was comparatively preserved after cryopreservation, but mitochondrial function of the cusps was more diminished.

Animals↗

Mössbauer studies on laser evaporated iron atoms and their reactions with oxygen in argon matrices.

Laser-evaporated iron atoms were isolated in low-temperature Ar matrices and their chemical reactions with oxygen were investigated by means of Mössbauer spectroscopy. Reactions of iron atoms with oxygen produce FeO, Fe(O2), FeO3, (O2)FeO2 and OFeO isolated in the Ar matrices and their yields vary depending on the concentration of oxygen. Similarly, FeO and Fe(O2) were obtained by the reaction of iron atoms with N2O. Infrared spectroscopy and molecular orbital calculations were applied to support their assignments.

Calorimetry↗

Diaphanous-related formins bridge Rho GTPase and Src tyrosine kinase signaling.

We have examined the role of the mouse Diaphanous-related formin (DRF) Rho GTPase binding proteins, mDia1 and mDia2, in cell regulation. The DRFs are required for cytokinesis, stress fiber formation, and transcriptional activation of the serum response factor (SRF). 'Activated' mDia1 and mDia2 variants, lacking their GTPase binding domains, cooperated with Rho-kinase or ROCK to form stress fibers but independently activated SRF. Src tyrosine kinase associated and co-localized with the DRFs in endosomes and in mid-bodies of dividing cells. Inhibition of Src also blocked cytokinesis, SRF induction by activated DRFs, and cooperative stress fiber formation with active ROCK. Our results show that the DRF proteins couple Rho and Src during signaling and the regulation of actin dynamics.

3T3 Cells↗

A powerful aromatic volatile thiol, 2-furanmethanethiol, exhibiting roast coffee aroma in wines made from several Vitis vinifera grape varieties.

The chemical compound 2-furanmethanethiol (2FM), with a strong roast coffee aroma, has been identified in sweet white wines made from the Petit manseng grape variety, and in certain red Bordeaux wines (made from the Merlot, Cabernet franc, and Cabernet sauvignon grape varieties). This was done by extracting specific volatile thiols using p-hydroxymercuribenzoate. The 2FM has also been found in toasted oak used in barrel-making. All the Petit manseng sweet white wines and some of the red Bordeaux wines analyzed contained between a few ng/L and several dozen ng/L of 2FM. Taking into account its very low perception threshold (0.4 ng/L in a model hydro alcoholic environment), 2FM could therefore contribute to the roast coffee aroma of certain wines.

Chromatography, Gas↗