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Biomedical subjects

T Tominaga

Publications and source records attributed to T Tominaga.

At least 163 records · Page 9Linked to original sources

Bilateral horizontal gaze palsy with pontine cavernous hemangioma: a case report.

A 31-year-old man demonstrating acquired bilateral gaze palsy as an isolated symptom of a paramedian pontine reticular formation (PPRF) lesion due to a ruptured cryptic cavernous hemangioma is herein reported. MRI revealed a flow void surrounded by a hemorrhagic lesion, which was located in the lower dorsal part of the pons. This lesion corresponded to the PPRF. His eye movement almost completely recovered and MRI revealed the absorption of the hematoma 2 months later, with only conservative observation. This is a rare case presenting most likely with a minimal lesion for bilateral gaze palsy. Based on the above findings it is thus concluded that surgical removal of such a cryptic cavernous hemangioma should therefore not be the only choice.

Adult↗

The contractile vacuole fluid discharge rate is determined by the vacuole size immediately before the start of discharge in Paramecium multimicronucleatum

The precise relationship between the rate of contractile vacuole fluid discharge and the vacuole diameter at the start of systole was determined in cells of Paramecium multimicronucleatum subjected to various external conditions. The rate of discharge was higher when the diameter was larger. When the rate of discharge was plotted against the diameter, the points fell around a single parabolic line passing through the origin and were independent of the external conditions employed. This implies that the rate of discharge is proportional to the square of the vacuole diameter. We have previously proposed a hypothesis in which membrane tension in the contractile vacuole is altered as its planar membrane becomes tubular or as tubules become planar membrane (termed the membrane area-proportional tension hypothesis). We propose here that it is this change in membrane tension which determines the vacuole pore shape and sets the subsequent rate of fluid discharge.

Journal Article↗

How does the contractile vacuole of Paramecium multimicronucleatum expel fluid? Modelling the expulsion mechanism

To examine the forces needed for discharge of the fluid contents from the contractile vacuole of Paramecium multimicronucleatum, the time course of the decrease in vacuole diameter during systole (the fluid-discharging period) was compared with that of various vacuole discharge models. The observed time course did not fit that predicted by a model in which contraction of an actin­myosin network surrounding the vacuole caused discharge nor that predicted by a model in which the surface tension of the lipid bilayer of the vacuole caused discharge. Rather, it fitted that predicted by a model in which the cell's cytosolic pressure was responsible for discharge. Cytochalasin B, an effective inhibitor of actin polymerization, had no effect on the in vivo time course of systole. An injection of a monoclonal antibody raised against the proton pumps of the decorated spongiomes (now known to be the locus of fluid segregation in P. multimicronucleatum) disrupted the decorated spongiomes and reduced the rate of fluid segregation, whereas it did not alter the time course of systole. We conclude that in P. multimicronucleatum the internal pressure of the contractile vacuole is caused predominantly by the cytosolic pressure and that the fluid-segregation mechanism does not directly affect the fluid-discharge mechanism. Elimination of this cytosolic pressure by rupturing the cell revealed the presence of a novel fluid-discharge mechanism, apparently centered in the vacuole membrane. The involvement of tubulation of the vacuole membrane as the force-generating mechanism for fluid discharge in disrupted cells is discussed.

Journal Article↗

Adult respiratory distress syndrome in patients with malignant astrocytoma--three case reports.

Three patients treated for intracranial malignant astrocytomas developed adult respiratory distress syndrome (ARDS). All three patients had a Karnofaky performance status score of at least 80% and similar clinical characteristics. All demonstrated hypersensitivity to phenytoin. ARDS occurred in two patients during radiotherapy and in one with radiation-induced brain damage following initial radiochemotherapy. ARDS occurred shortly after tapering the long-term administration of betamethasone. The initial symptoms were dry cough, fever, and generalized toxic eruption. Serum lactic acid dehydrogenase (LDH) concentrations were increased up to 2500 IU/l. Several days later, the patients suddenly complained of dyspnea. All patients fulfilled the diagnostic criteria for ARDS. Two patients recovered, but a young woman died. Clinical symptoms such as fever of unknown origin, dry cough and skin eruptions, accompanied by abnormally increased serum LDH concentrations during or following the tapering of long-term administration of corticosteroids, are warning signs of ARDS in patients being treated for malignant gliomas.

Adult↗

[Determination of intratumoral estrone (E1) and estradiol (E2) in primary breast cancer tissues by sensitive HPLC-RIA].

The alternation of intratumoral estrogen metabolism has been indicated in breast cancer tissues. We determined the intratumoral concentrations of estrone (E1) and estradiol (E2) by a sensitive HPLC-radioimmunoassay (RIA) and analyzed its clinical significance in 74 primary breast cancer tissues. The average intratumoral concentrations of E1 were 48.6 + 7.3 pg/g w.w and 80.6 + 43.2 pg/g w.w in pre- and post-menopausal patients, respectively. The E2 concentrations were 168.7 + 36.8 pg/g w.w and 104.7 + 23.6 pg/g in pre- and post-menopausal patients, respectively. The background analysis demonstrated that intratumoral E2 levels were significantly higher in estrogen receptor (ER) positive tumors compared to ER negative tumors (p < 0.01). A significant correlation was also found between intratumoral E2 concentrations and progesterone receptor (PgR) status, indicating that E2 synthesis is frequently upregulated in hormone dependent tumors. These findings are important for studying the hormonal microcircumstances of Japanese breast cancer patients and also for considering the indication for clinical treatment using aromatase inhibitors.

Adult↗

[Spontaneous spinal epidural hematoma: case report].

We report a case of spontaneous spinal epidural hematoma (SSEH) at the upper thoracic level which accompanied an epidural vascular lesion demonstrated by histological examination. A 62-year-old male was referred to our department, because of sudden onslaught of back pain, progressive paraparesis, and sensory disturbance below the dermatome of Th8. He had no history of a tendency to bleed, anticoagulant therapy, or trauma. There was no abnormality in the laboratory data. MRI revealed that an epidural mass at the level of dorsal T1 and T2 was compressing the spinal cord. Multilevel spondylotic change and thickened yellow ligament were also noted. Sixteen hours after the onset, we performed laminectomy at T1 and T2 and evacuated the epidural hematoma. An unusual vascular-net like tissue was found on the dura mater after removal of the hematoma. Postoperatively, neurological symptoms disappeared within three weeks. Histological appearance of the vascular tissue was a cluster of vessels containing a dilated vein with partially thin wall due to lack of elastic and collagen fibers. In reviewing the literature, there are several reports describing vascular lesions, such as cavernous angioma and AVM, as possible etiologies of SSEH. In the present case, long lasting compression of the posterior epidural venous plexus by the thick yellow ligament might have resulted in formation of an abnormal vein which ultimately caused bleeding.

Dura Mater↗

[The feasibility of CEF (cyclophosphamide, epirubicin, 5-FU) regimen in the adjuvant setting of primary breast cancer].

In Japan, 5-FU/5-FU derivatives or the combination therapy of CAF (cyclophosphamide, CPA; adriamycin, ADM; 5-fluorouracil; 5-FU) have been commonly used for the adjuvant treatment of breast cancer. Recently, a combination of CEF (CPA; Epirubicin, EPI; 5-FU) has come to the stage of adjuvant setting, because the cardiotoxicity was reduced in EPI. In this study, we investigated the feasibility of 6 cycles of CEF (CPA 700 mg/m2, EPI 70 mg/m2, 5-FU 700 mg/m2; day 1 iv every 3-4 weeks) in the adjuvant treatment of primary breast cancer patients with nodal involvements. All 12 patients completed 6 cycles of CEF within 8 months. The median treatment duration was 6.2 months. More than Grade III side effects of neutropenia, nausea/vomiting and alopecia were observed in 7/12 (58.3%), 5/12 (41.7%) and 12/12 (100%), respectively. No serious side effects, including cardiotoxicity, were shown. CEF seems to be feasible regimen as an adjuvant treatment for breast cancer.

Adult↗

[Fatal brain stem infarction due to rupture of a brain abscess: a case report].

We report a case of a brain abscess which initially presented with subcortical hematoma and ultimately resulted in fatal brain stem infarction due to its rupture into the subarachnoid space. A 50-year-old male was admitted to a nearby hospital with complaints of headache, fever, and sensory aphasia. He had ventricular septal defect found 15 years previously, sinusitis, and liver cirrhosis. Computerized tomographic (CT) scan revealed a left temporal subcortical hematoma. Gadolinium-DTPA enhanced magnetic resonance imaging (MRI) showed faint ring-like enhancement at the margin of the lesion. The left internal carotid angiogram demonstrated the vascular blush and early venous filling of the vein of Labbé. Administration of antibiotics and predonine resulted in resolution of fever within five days. MRI obtained 17 days after the onset showed typical ring-like enhancement. The mass was just adjacent to the lateral ventricle. The patient was transferred to our hospital for further examination and treatment 21 days after the onset. Fever had recurred 2 days before admission to our hospital. One day after admission, the patient began to vomit. About 15 hours following this symptom, he suddenly became comatose and tetraplegic. CT scan demonstrated a rupture of the abscess. Emergent drainage from the lateral ventricle and the abscess cavity was undertaken. Follow-up CT scan revealed multiple infarctions involving the upper brain stem and the bilateral thalamus. He died on the 29th day after the onset. The mechanisms of hemorrhage with a brain abscess and cerebral infarction after rupture of brain abscess are discussed. Hemorrhage with brain abscess is extremely rare. However, brain abscess should be considered as a possible etiology of an atypical hematoma. To avoid fatal rupture of the brain abscess, immediate treatment is essential. Once the rupture of the brain abscess occurs, its contents might cause vasospasm severe enough to cause cerebral infarction.

Brain Abscess↗

Indication of chemoembolization therapy without gelatin sponge for hepatocellular carcinoma.

This study evaluated the effect of chemoembolization (C-LIP) consisting of ethiodized oil (Lipiodol Ultra Fluid; André Guerbet, Aulnay-sous-Bois, France) and epirubicin, without gelatin sponge on hepatocellular carcinoma (HCC), administered by hepatic arterial infusion. We analyzed the cases from two points of view: the local recurrence rate for hypervascular solitary small HCC (tumor size: < or =3 cm in diameter) and the cumulative survival rate for advanced HCC (stage VI according to the criteria of Liver Cancer Group of Japan) following C-LIP therapy. The C-LIP also was compared with transcather arterial embolization (TAE; C-LIP followed by gelatin sponge) and percutaneous ethanol injection therapy (PEIT). In the small HCC cases, the recurrence rate at 1 year after C-LIP was 77% (10 of 13 patients), while the local recurrence rate was 46% (six of 13 patients) at 6 months and 61% (eight of 13 patients) at 1 year. The local recurrence rate at 1 year was 29% (four of 14 patients) after TAE and 20% (three of 15 patients) after PEIT. These results showed that the effect of local anticancer therapy by C-LIP was not as potent as that of TAE or PEIT. In advanced HCC cases, the cumulative survival rate for 13 patients treated by C-LIP was 72% at 6 months, 36% at 1 year, and 14% at 2 years. However, the survival rates for 13 patients at 6 months, 1 year, and 2 years after TAE were 46%, 23%, and 8%, respectively. There was no difference between the C-LIP patients and TAE patients with regard to the pretreatment liver function. Three patients died within 2 months after the initial TAE. These deaths were mainly due to damage to the noncancerous liver parenchyma. Therapy with C-LIP alone was not appropriate for hypervascular solitary small HCCs, and additional treatment was necessary. We think C-LIP therapy should be selected instead of TAE for advanced HCCs to avoid severe parenchymal damage.

Aged↗

Biomechanical evaluation of hydroxyapatite intervertebral graft and anterior cervical plating in a porcine cadaveric model.

The biomechanical properties of a porous hydroxyapatite (HA) intervertebral graft with or without anterior cervical plating were evaluated in cadaveric porcine cervical spine model using C3-4 discectomy and dissection of the posterior longitudinal ligament to cause instability. The experimental groups were intact (n = 11), instability (n = 11), autogenous bone implant (n = 6), HA graft implant (n = 5), autogenous bone with plating (n = 6), and HA graft with plating (n = 5). Porous HA with 40% porosity and scapular bone were used as grafts. The displacement rates of the cervical spine by compressive forces in the flexural, extensional, and lateral bending directions were evaluated using video-recording followed by computer-assisted analysis. The stiffness to compressive load was calculated from the load-displacement rate curve. The linear and non-linear coefficients of the Fung's equation were obtained based on the plot of Young's modulus against load. There were no statistical differences in the stiffness between the HA and autogenous bone graft in all directions. The two plating groups showed significantly increased stiffness in all directions. The non-linear coefficient value in Fung's equation was far larger in both HA and HA graft with plating groups than in the other groups in flexural compression. Porous HA graft has a compressive strength similar to autogenous graft in vitro, and anterior plating provides additional stiffness to the cervical spine. The larger non-linear coefficient value of the HA groups may represent the characteristic biomechanical brittleness of HA graft, but this is manifest only in flexural compression.

Animals↗

[Prospective controlled study on the usefulness of Carmofur as a postoperative adjuvant chemotherapy for colorectal cancer].

A prospective controlled study, the 7th cooperative study of the Japanese Foundation for Multidisciplinary Treatment, was conducted to evaluate the usefulness of concomitant therapy with MMC + HCFU as a postoperative adjuvant therapy in patients with colorectal cancer who had undergone curative resection for a period of 2 years and 11 months from February, 1986. The Dukes B and C patients with colorectal cancer classified by macroscopic examination who had an intravenous MMC 6 mg/m2 on the day of operation and followed by oral HCFU for 12 months from 2 weeks after operation (Group X) were compared with patients who had operation only (Group Y). Some 978 patients with colon cancer and 713 patients with rectal cancer were enrolled in the study, 85 (5.0%) of whom were not eligible. The 5-year survival rate of Group X in colon cancer was 79.3% and that of Group Y was 76.4%: thus the survival rate of Group X was slightly better than that of Group Y, but no significant difference was found between the two groups. Subset analysis revealed that the survival rate of Group X in advanced cancer of stage III b + IV, according to the General Rules for Clinical and Pathological Studies on Cancer of the Colon, Rectum and Anus in Japan, was 62.4% and that of Group Y was 46.2%. Thus, the survival rate of Group X was significantly better than that of Group Y (logrank test: p = 0.035, generalized Wilcoxon test: p = 0.025). The disease-free survival rate was not significantly different between the groups with colon cancer and rectal cancer. The above results suggest that HCFU is useful for patients with a high risk of recurrence who had advanced colon cancer (stage III b + IV). However, additional prospective studies are required to verify them.

Antineoplastic Combined Chemotherapy Protocols↗

[New molecular target of cancer therapy--angiogenesis regulator VEGF].

Recent studies on angiogenesis in human solid tumors have underlined its importance as therapeutic target. In particular, of interest is to suppress the function of several positive regulators including vascular endothelial growth factors (VEGF), basic fibroblast growth factor and thymidine phosphorylase, because they are evident to be responsible for the promotion of neovascularization in a variety of tumor types. In this review, we picked up VEGF, probably one of most promising target, and discuss about the therapeutic tools for controlling VEGF function in human tumors.

Antibiotics, Antineoplastic↗

Hepatitis C virus genotypes in the United States: epidemiology, pathogenicity, and response to interferon therapy. Collaborative Study Group.

OBJECTIVE: To study 1) the geographic distribution and clinical significance of hepatitis C virus (HCV) genotypes in the United States and 2) the influence of HCV genotypes on response to interferon therapy. DESIGN: Hepatitis C virus genotype was determined in 179 stored serum samples obtained from patients who were positive for antibody to HCV and for HCV RNA by using polymerase chain reaction. SETTING: Tertiary referral centers in four geographic regions of the United States. PATIENTS: Patients who visited medical centers in the Midwest (50 patients), Northeast (42 patients), Southeast (35 patients), and West (52 patients). MEASUREMENTS: Chaotropic lysis and isopropanol precipitation were used to extract RNA from serum. Polymerase chain reaction was done on the NS5 region and was followed by automated direct sequencing and genotyping of desalted amplification products. RESULTS: 104 patients (58%) had subtype 1a; 38 (21%) had subtype 1b; 4 (2%) had subtype 2a; 23 (13%) had subtype 2b; 8 (5%) had subtype 3a; and 2 (1%) had subtype 4a. Examination of the known risk factors for acquiring HCV showed no association between genotype and mode of acquisition (blood transfusion, injection drug use, employment at a health care facility) or histologic findings at presentation (mild active hepatitis, moderately active hepatitis, or cirrhosis). Sixty-eight percent of patients with genotype 1a, 80% of patients with genotype 1b, and 37% of patients with genotype 2a or 2b had severe hepatitis. Thirteen of 46 (28%) patients with genotype 1a and 4 of 15 (26%) patients with genotype 1b had a complete biochemical response after 6 months of interferon therapy. In contrast, 10 of 14 (71%) patients with genotype 2a or 2b had a complete response to interferon therapy. Five of 39 (13%) patients with genotype 1a, 1 of 14 (7%) patients with genotype 1b, and 2 of 11 (18%) patients with genotype 2a or 2b had a sustained biochemical response. CONCLUSIONS: In the United States, HCV genotypes 1a and 1b are the predominant genotypes in patients with chronic hepatitis C. Genotype is not correlated with mode of virus acquisition or with histologic findings at presentation. Patients with HCV genotype 1a or 1b had more severe liver disease and lower rates of response to interferon therapy than did patients with HCV genotype 2a or 2b. These findings may have implications for predicting outcome and selecting patients for interferon treatment.

Adult↗

Enhanced fast synaptic transmission and a delayed depolarization induced by transient potassium current blockade in rat hippocampal slice as studied by optical recording.

In hippocampal neurons, a slowly inactivating aminopyridine-sensitive transient potassium current, D-current, influences the time course of action potential repolarization and therefore activity-dependent Ca2+ entry. We used high-speed optical recording techniques to study the effects of selectively inhibiting D-current with 4-AP (40 microM) on transmission at the Schaffer collateral (CA3)-CA1 synapse in rat hippocampal slices stained with the voltage-sensitive dye RH-155. We observed that addition of 4-AP to the bathing solution resulted in (1) augmentation of a fast component of the optical signal corresponding to the postsynaptic EPSP and action potential, and (2) the appearance of a delayed depolarization of CA1 neurons and other adjacent cells. 4-AP appeared to alter the presynaptic action potential and the dynamics of synaptic transmission to both reduce the sensitivity of the postsynaptic EPSP and action potential to omega-toxin calcium channel blockers (omega-conotoxin GVIA and omega-agatoxin IVA) and the Ca(2+)-dependent potassium channel blocker charybdotoxin, and to increase sensitivity to the dihydropyridine nifedipine, the NMDA receptor blocker aminophosphonopentanoic acid, and the intracellular Ca2+ release inhibitor thapsigargin. The delayed depolarization induced by 4-AP was inhibited in hyperosmotic extracellular solution, suggesting that enhanced transmitter release resulted in increased accumulation of K+ in the extracellular space. Because 4-AP is a convulsant at concentrations similar to those used here, we suggest that the 4-AP-targeted channel(s) carrying D-current may contribute to the hyperexcitability associated with epilepsy.

4-Aminopyridine↗

Prognostic factors for patients with colon or rectal carcinoma treated with resection only. Five-year follow-up report.

BACKGROUND: The prognostic factors and natural history of recurrence in patients with colorectal carcinoma who underwent curative resection and no other therapy were analyzed. METHODS: The object of analysis was the potentially curative resection only subgroup in the randomized clinical trial (RCT) that we performed. Cox's proportional hazards model was used mainly to analyze recurrence rates during the first 5 years after surgery. RESULTS: The analysis was performed on a subgroup of the RCT (279 patients with colon carcinoma and 293 patients with rectal carcinoma). Five-year disease free survival rates were 76.3% and 56.5% for colon and rectal carcinomas, respectively. The prognostic factors for recurrence for colon carcinoma patients were different from those with rectal carcinoma. For colon carcinoma, only Dukes stage was significant, whereas for rectal carcinoma, Dukes stage, age, location of the tumor, and serosal and venous invasion by cancer cells were prognostic factors. Log-transformed disease free survival rates were linear in Dukes Stage B and biphasic in Dukes Stage C for both colon and rectal carcinoma. The two phases in Dukes Stage C intersected at 2.85 and 3.04 years, respectively. The annual hazard value was high for the first 3 years in both colon and rectal carcinoma. CONCLUSIONS: We conclude that follow-up of patients with colorectal carcinoma who undergo potentially curative resection is of particular importance in the first 3 years after surgery. Furthermore, the usefulness of adjuvant chemotherapy can be adequately evaluated from data yielded during this postoperative period.

Chemotherapy, Adjuvant↗

Expression of heme oxygenase and inducible nitric oxide synthase mRNA in human brain tumors.

Heme oxygenase-1, a key enzyme in heme catabolism, and inducible nitric oxide synthase (iNOS) are responsible for production of carbon monoxide and nitric oxide (NO), respectively. Expression of each enzyme has been shown to be modulated by heme and NO, raising a possibility for the coordinated regulation of the two enzymes. We therefore analyzed the expression levels of both mRNA in humans using brain tumors. Either heme oxygenase-1 or iNOS mRNA was expressed at higher levels in brain tumors compared to the brain tissue, but their expression levels were not apparently correlated. In the brain tumor cell lines, treatment with cytokines increased the expression of iNOS mRNA but not heme oxygenase-1 mRNA, whereas treatment with an NO donor increased the expression of heme oxygenase-1 mRNA but not iNOS mRNA. These results suggest the separate regulation of expression of both enzyme mRNA in humans.

Adult↗

Entorhinal-hippocampal interactions revealed by real-time imaging.

The entorhinal cortex provides the major cortical input to the hippocampus, and both structures have been implicated in memory processes. The dynamics of neuronal circuits in the entorhinal-hippocampal system were studied in slices by optical imaging with high spatial and temporal resolution. Reverberation of neural activity was detected in the entorhinal cortex and was more prominent when the inhibition due to gamma-aminobutyric acid was slightly suppressed. Neural activity was transferred in a frequency-dependent way from the entorhinal cortex to the hippocampus. The entorhinal neuronal circuit could contribute to memory processes by holding information and selectively gating the entry of information into the hippocampus.

Animals↗