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Biomedical subjects

H Murai

Publications and source records attributed to H Murai.

At least 55 records · Page 3Linked to original sources

Total spondylectomy for solitary spinal metastasis of the thoracolumbar spine: a preliminary report.

Eight cases of solitary spinal metastasis with neurological deficit in thoracolumbar spine in which total en bloc spondylectomy (TS) was performed by bisecting the affected vertebra through both pedicles using fine thread wire saws were reviewed. Patient age ranged from 40 to 78 (mean, 62) years. Primary lesions were in the lung (2), kidney (2), thyroid (3) and prostate (1). TS was performed through a posterior approach in 5 cases (T6-7, T12, L2, L2 and L2-3) and through a one-stage anterior and posterior combined approach in the others (L2, L3 and L4). The spine was reconstructed with a ceramic vertebral prosthesis and a pedicle screw fixation system in 5 cases, and with augmented anterior spinal instruments in 3 cases. There were neither surgical complications nor surgical mortality. All patients became ambulatory and pain-free after surgery. Histologically, a marginal surgical margin was achieved in only one case. The other 7 cases had intralesional margin at the osteotomized pedicles. Four patients died from causes unrelated to local recurrence 4 to 44 (mean, 19) months after surgery. Effectiveness of surgery was maintained until death in all 4 of these patients. Asymptomatic local recurrence occurred in 2 patients with renal cancer at 10 and 33 months after surgery. These preliminary results suggest that TS for solitary spinal metastasis can achieve good control of local recurrence without major complications and is clinically acceptable surgery.

Adult↗

[Repeated deterioration of tuberculous meningitis due to a reduction in the corticosteroid dosage during chemotherapy].

A 17-year-old man with a high fever, confusion and neck stiffness was diagnosed to have tuberculous meningitis, and was immediately placed on prednisolone (40 mg/day) as well as standard antituberculosis drugs (isoniazid, rifampicin and pyrazinamide). The clinical symptoms improved rapidly and the number of cerebrospinal fluid(CSF) cells decreased from 1837/mm3 on admission to 76/mm3 on the 7th day. Thereafter the dosage of prednisolone was gradually reduced. As a result, however increased nuchal rigidity, papilloedema and an increase in the number of CSF cells of 934/mm3 were all observed on the 35th day. Prednisolone thus again administered at the original dosage and the patient quickly showed a clinical improvement. CSF cells decreased to 271/mm3 on the 70th day. When prednisolone was again tapered down, increased nuchal rigidity, abducent nerve palsy and papilloedema appeared again with a marked increase in the number of CSF cells of 1309/mm3 on the 91th day. Therefore, we continued to treat the patient with prednisolone, in addition to the standard antituberculosis treatment, at a dose of 80 mg/day and tapered off very slowly over six months. This treatment resulted in a marked recovery with no recurrence. In this case, prednisolone was indispensable for treating tuberculous meningitis in combination with appropriate antituberculosis drugs, though the role of corticosteroids has remained controversial over the years. This case might be an example of paradoxical progression in tuberculous meningitis.

Adolescent↗

Structure of the HIV-1 integrase catalytic domain complexed with an inhibitor: a platform for antiviral drug design.

HIV integrase, the enzyme that inserts the viral DNA into the host chromosome, has no mammalian counterpart, making it an attractive target for antiviral drug design. As one of the three enzymes produced by HIV, it can be expected that inhibitors of this enzyme will complement the therapeutic use of HIV protease and reverse transcriptase inhibitors. We have determined the structure of a complex of the HIV-1 integrase core domain with a novel inhibitor, 5ClTEP, 1-(5-chloroindol-3-yl)-3-hydroxy-3-(2H-tetrazol-5-yl)-pro penone, to 2.1-A resolution. The inhibitor binds centrally in the active site of the integrase and makes a number of close contacts with the protein. Only minor changes in the protein accompany inhibitor binding. This inhibitor complex will provide a platform for structure-based design of an additional class of inhibitors for antiviral therapy.

Binding Sites↗

Identification of Cancer Antigens in Breast Cancer by the SEREX Expression Cloning Method.

Enormous strides in cancer immunology have been made during the past decade. This is largely due to the development of methodologies capable of defining the antigenic targets on cancer cells that elicit a host immune response. The molecular cloning of antigens recognized by cytotoxic T cells by Boon and his colleagues has provided a growing list of tumor antigens, particularly for melanoma, that allows detailed monitoring of T cell responses to these antigens and offers promising targets for cancer vaccine development. An alternative new method, SEREX, for the serological identification of cancer antigens has been developed by Pfreundschuh and his colleagues. SEREX can be applied to all types of cancer including breast cancer that have been unapproachable by using cytotoxic T cells and thus offers an opportunity to define a vast range of cancer antigens. Toward thedevelopment of a vaccine for breast cancer, we have begun using SEREX to study breast cancer and have identified a few promising cancer antigens. Each antigen is now being critically evaluated as a possible vaccine target.

Journal Article↗

Surface strain distribution on thoracic and lumbar vertebrae under axial compression. The role in burst fractures.

STUDY DESIGN: The surface strain distribution on the thoracic and lumbar vertebrae during axial compressive loading was examined. OBJECTIVES: To examine the general mechanical behavior of the thoracic and lumbar vertebrae to evaluate their role in burst fractures. SUMMARY OF BACKGROUND DATA: Burst fractures are generally characterized by injury to the middle column and fracturing of the superior endplate. However, results in previous biomechanical investigations have not shown how these fractures are initiated during compression. METHODS: Twenty-one thoracic and lumbar vertebrae (5 T10, 10 L1, and 6 L4) with upper and lower vertebrae were studied. Three-axis rosette strain gauges were cemented to 11 sites on the vertebral surface. An axial compressive load was applied, and the strain was measured in each specimen. The strain recorded by each rosette gauge was converted into a tensile, compressive, and shear component. RESULTS: The highest tensile and compressive strain was recorded at the base of the pedicle. Shear strain in the vertebral body was significantly higher than that in the lamina at all three spinal levels. At L1 and L4, the tensile strain at the superior vertebral rim was higher than that at the inferior rim. CONCLUSIONS: The high tensile and compressive strains found at the base of the pedicle of T10, L1, and L4 indicate that the base of the pedicle is the site of fracture initiation. The higher tensile strain at the superior vertebral rim of L1 and L4 supports the clinical observation of the thoracolumbar burst fractures.

Aged↗

Dietary prevention of azoxymethane-induced colon carcinogenesis with rice-germ in F344 rats.

The modifying effect of dietary administration of defatted rice-germ and gamma-aminobutyric acid (GABA)-enriched defatted rice-germ on azoxymethane (AOM)-induced colon carcinogenesis was investigated in two experiments with male F344 rats. In the first experiment (the pilot study), the effects of the defatted rice-germ, the GABA-enriched defatted rice-germ and rice-germ on AOM-induced (15 mg/kg body wt once a week for 3 weeks) formation of aberrant crypt foci (ACF) were examined. The latter two preparations (2.5% in the diet) significantly inhibited ACF formation (P < 0.005). In the second experiment, a long-term study of the effects of rice-germ was done. One group was treated with AOM alone, four groups received the carcinogen and were fed the diets containing 2.5% rice-germ or 2.5% GABA-enriched defatted rice-germ for 5 (initiation phase) or 30 weeks (post-initiation phase), two groups were treated with rice-germ or GABA-enriched defatted rice-germ alone and one group was kept on the basal diet. At the termination of the study, dietary exposure to rice-germ during the initiation phase significantly reduced the incidence of colonic adenocarcinoma (71 versus 29%, P < 0.01). GABA-enriched defatted rice-germ or rice-germ during the post-initiation phase also decreased the frequency of colonic adenocarcinoma (71 versus 20%, GABA-enriched defatted rice-germ feeding, P < 0.01; 27%, rice-germ feeding, P < 0.01). These data suggest that constituents of rice-germ are possible dietary preventatives for human colon cancers.

Animals↗

A dose-finding study of lenograstim (glycosylated rHuG-CSF) for peripheral blood stem cell mobilization during postoperative adjuvant chemotherapy in patients with breast cancer. Lenograstim/Breast Cancer Study Group.

BACKGROUND: The optimum dose of granulocyte colony-stimulating factor (G-CSF) for peripheral blood stem cell (PBSC) mobilization after disease-oriented, conventional-dose chemotherapy remains unknown. METHODS: A multicenter dose-finding study of glycosylated G-CSF (lenograstim) for the mobilization of PBSCs following adjuvant CAF chemotherapy (cyclophosphamide, doxorubicin and 5-fluorouracil) was performed in 38 patients with postoperative breast cancer. Each 10, ten and eight patients were sequentially allocated to one of the three dose groups (2, 5 and 10 micrograms/kg, respectively) of lenograstim. Lenograstim was administered subcutaneously (s.c.) daily from day 8 to the day of the last apheresis and CD34+ cells and colony-forming units-granulocyte macrophage (CFU-GMs) in peripheral blood were measured serially. Additionally, 10 patients who received adjuvant CAF chemotherapy alone also participated in the study, as a control. RESULTS: Lenograstim was well tolerated up to 10 micrograms/kg, except for one patient given 10 micrograms/kg who developed transient grade 3 hepatic enzyme elevation. The peak levels of CD34+ cells and CFU-GMs in peripheral blood showed dose-response relationships. The median peak CD34+ cells for the 0, 2, 5 and 10 micrograms/kg dose groups were 5.4, 34.3, 55.0 and 127.6 cells/microliter, respectively, and those of CFU-GMs for the 0, 2, 5 and 10 micrograms/kg dose groups were 0.01, 0.33, 1.32 and 3.30 CFU-GMs/microliter, respectively. CONCLUSIONS: Considering the previous reports suggesting that a pre-apheresis number of 40-50 CD34+ cells/microliter in peripheral blood is highly predictive for achievement of more than 2.5 x 10(6) CD34+ cells/kg in a standard apheresis procedure of 10 litres, the optimum dose of lenograstim for PBSC mobilization following CAF chemotherapy in patients with postoperative breast cancer is 5 micrograms/kg/day s.c.

Adjuvants, Immunologic↗

Schwannoma of the oculomotor nerve: a case report with consideration of the surgical treatment.

OBJECTIVE AND IMPORTANCE: Oculomotor schwannoma is extremely rare. We report a case of oculomotor schwannoma with consideration of its surgical management. CLINICAL PRESENTATION: A 64-year-old woman with a history of chronic headache underwent a computed tomographic scan, which revealed a mass lesion in the right prepontine cistern. She had no neurological deficits at admission. INTERVENTION: The tumor originated from the right oculomotor nerve. It was subtotally removed, leaving a tiny part attached to the nerve. The nerve trunk was preserved. A pathological examination revealed a schwannoma. Transient right oculomotor nerve palsy occurred postoperatively, but it improved almost completely. CONCLUSION: The tumor in the present case was resected, preserving serviceable oculomotor function. However, among 16 patients reported in the literature, all but one developed or maintained severe postsurgical oculomotor nerve palsy. We conclude that surgical resection generally is not indicated for oculomotor schwannomas, excluding large tumors that cause intractable symptoms.

Cranial Nerve Neoplasms↗

Dermatomyositis associated with invasive thymoma.

We report a case of dermatomyositis (DM) associated with invasive thymoma in a 22-year-old woman who was admitted to our hospital complaining of dyspnea which required ventilation support. The reddened elevated scaly eruptions were prominent over the extensor surfaces. Chest X-ray and computed tomography showed mediastinal masses, which were diagnosed as mixed type thymoma. Muscle and skin biopsy specimens were compatible with DM. She was treated with methylprednisolone pulse therapy followed by extended removal of the anterior mediastinal tumor and subsequent radiotherapy. She has had a good clinical course without recurrence of thymoma or DM for more than 3 years. The role of thymoma in the development of DM is discussed.

Adult↗

[Clinical effect of arotinolol hydrochloride and its influence on renal function in elderly patients with essential hypertension].

Arotinolol hydrochloride with alpha-and beta-receptor blocking action, developed in Japan, is mainly used for the treatment of hypertension. The study population consisted of 42 outpatients with essential hypertension with a blood pressure greater or equal to 160/96 mmHg. 10 men and 32 women, with a mean age of 77.5 year. The patients received 10 mg arotinolol hydrochloride daily for 24 weeks which was taken orally twice a day. We evaluated the changes of blood pressure, heart rate and chief complaints of patients before and every 4 weeks during treatment and the renal function before, 12 weeks after and 24 weeks after, the administration of arotinolol hydrochloride. Blood pressure and heart rate decreased significantly after 4 weeks of treatment with arotinolol hydrochloride (p < 0.05). However, no significant changes were found in blood urea nitrogen, serum creatinine, serum albumin, beta2-microglobuline, NAG or creatinine clearance during the 24 weeks of treatment. These results indicate that arotinolol hydrochloride has antihypertensive effects without renal dysfunction in elderly patients with essential hypertension.

Adrenergic alpha-Antagonists↗

[A case of cerebellar degeneration showing amaurosis fugax due to primary angle-closure glaucoma].

We reported a 76-year-old woman with cerebellar degeneration who had transient monocular visual loss following the acute attacks of angle-closure glaucoma. The episodes occurred only at night approximately every ten days. She denied pain or any other associated symptoms. Ophthalmological examinations including intraorbital pressure, ocular fundus, visual acuity and visual field showed no abnormalities between the attacks. Provisional diagnosis on admission was amaurosis fugax from retinal embolization. After admission, she developed a typical acute attack of glaucoma accompanied by severe pain in her left eye. Intraorbital pressures were 12 mmHg in the right eye and 58 mmHg in the left, and the diagnosis of primary angle-closure glaucoma was made gonioscopically. Following peripheral iridotomy by laser therapy, her visual acuity recovered and episodes of visual loss disappeared. In this case, the attacks of glaucoma were unusually painless, so it is very difficult to distinguish between glaucoma and amqurosis fugax from retinal embolization. The transient visual loss always occurred at night, and retrospectively, this characteristic feature might indicate that these episodes were acute attacks of angle-closure glaucoma. Glaucoma is one of the diseases that can cause painless amaurosis fugax.

Aged↗

A Randomized Controlled Trial on the Prevention of Seroma after Partial or Total Mastectomy and Axillary Lymph Node Dissection.

BACKGROUND: Wound seroma is one of the most frequent complications of mastectomy, but an effective strategy for its prevention has not yet been established. The purpose of this study was to determine the effectiveness of delayed shoulder exercise on the prevention of wound seroma after partial or total mastectomy with axillary dissection for the treatment of cancer. METHODS: This study prospectively randomized two exercise schemes after mastectomy with axillary lymph node dissection. The immediate exercise group (n =58) started shoulder exercise on the first postoperative day. In the delayed exercise group (n =58) the movement of the upper limb was limited to usual daily activities during the first postoperative week. RESULTS: Preoperative levels of shoulder function were regained within one month when shoulder exercise was delayed for one week after operation. Significant decrease of drainage volume and lower incidence of seroma formation were seen in the delayed exercise group. CONCLUSION: These observations suggest that seven days of unrestricted moverment and avoiding active exercise of the shoulder joint, is the optimal routine reduce seroma formation after mastectomy.

Journal Article↗

Neutropenia associated with T-cell large granular lymphocyte leukemia: long-term response to cyclosporine therapy despite persistence of abnormal cells.

T-cell large granular lymphocyte (T-LGL) leukemia is clinically indolent, but is associated with severe neutropenia in approximately 50% of cases. The pathogenesis of the neutropenia is unclear. We report reversal of severe neutropenia associated with T-LGL leukemia in five patients treated with cyclosporine (CSA). All five had persistent neutrophil counts below 0.5 x 10(9)/L, two had agranulocytosis, and four had recurrent infections. Increased populations of LGL were present in blood and marrow, with a T-LGL immunophenotype (CD3(+)CD8(+)CD16(+/-)CD56(+/-)CD57(+)) shown by multiparameter flow cytometry, and clonal T-cell receptor (TCR) gene rearrangements in two of two pretreatment blood samples studied. CSA was initiated at doses of 1 to 1.5 mg/kg orally every 12 hours, with subsequent dose adjustments based on trough serum levels. Four patients attained normal neutrophil counts with CSA alone; one required addition of low-dose granulocyte-macrophage colony-stimulating factor. Time to attainment of 1.5 x 10(9)/L neutrophils ranged from 21 to 75 days. Attempts to taper and withdraw CSA resulted in recurrent neutropenia. Three patients have maintained normal neutrophil counts on continued CSA therapy for 2, 8, and 8.5 years. Two patients died 1.7 and 4.6 years after initiation of CSA despite normal neutrophil counts-one of metastatic melanoma and one of complications after aortofemoral bypass surgery. Despite resolution of neutropenia, increased populations of T-LGL cells have persisted in all patients during CSA therapy, as shown by morphology and flow cytometry and by the presence of clonal TCR gene rearrangements in four patients' posttreatment blood samples. We conclude that CSA is an effective therapy for neutropenia associated with T-LGL leukemia, and that resolution of neutropenia despite persistence of abnormal cells implies that CSA may inhibit T-LGL secretion of yet unidentified mediators of neutropenia.

Adult↗

Twofold overexpression of human beta-amyloid precursor proteins in transgenic mice does not affect the neuromotor, cognitive, or neurodegenerative sequelae following experimental brain injury.

By using transgenic mice that overexpress human beta-amyloid precursor proteins (APPs) at levels twofold higher than endogenous APPs, following introduction of the human APP gene in a yeast artificial chromosome (YAC), we examined the effects of controlled cortical impact (CCI) brain injury on neuromotor/cognitive dysfunction and the development of Alzheimer's disease (AD)-like neuropathology. Neuropathological analyses included Nissl-staining and immunohistochemistry to detect APPs, beta-amyloid (Abeta), neurofilament proteins, and glial fibrillary acidic protein, whereas Abeta levels were measured in brain homogenates from mice subjected to CCI and control mice by using a sensitive sandwich enzyme-linked immunosorbent assay. Twenty APP-YAC transgenic mice and 17 wild type (WT) littermate controls were anesthetized and subjected to CCI (velocity, 5 m/second; deformation depth, 1 mm). Sham (anesthetized but uninjured) controls (n = 10 APP-YAC; n = 8 WT) also were studied. Motor function was evaluated by using rotarod, inclined-plane, and forelimb/hindlimb flexion tests. The Morris water maze was used to assess memory. Although CCI induced significant motor dysfunction and cognitive deficits, no differences were observed between brain-injured APP-YAC mice and WT mice at 24 hours and 1 week postinjury. By 1 week postinjury, both cortical and hippocampal CA3 neuron loss as well as extensive astrogliosis were observed in all injured animals, suggesting that overexpression of human APPs exhibited no neuroprotective effects. Although AD-like pathology (including amyloid plaques) was not observed in either sham or brain-inj ured animals, a significant decrease in brain concentrations of only Abeta terminating at amino acid 40 (Abeta x-40) was observed following brain injury in APP-YAC mice (P < 0.05 compared with sham control levels). Our data show that the APP-YAC mice do not develop AD-like neuropathology following traumatic brain injury. This may be because this injury does not induce elevated levels of the more amyloidogenic forms of human Abeta (i.e., Abeta x-42/43) in these mice.

Amyloid beta-Peptides↗

Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin.

Glycogen synthase kinase-3 (GSK-3) mediates epidermal growth factor, insulin and Wnt signals to various downstream events such as glycogen metabolism, gene expression, proliferation and differentiation. We have isolated here a GSK-3beta-interacting protein from a rat brain cDNA library using a yeast two-hybrid method. This protein consists of 832 amino acids and possesses Regulators of G protein Signaling (RGS) and dishevelled (Dsh) homologous domains in its N- and C-terminal regions, respectively. The predicted amino acid sequence of this GSK-3beta-interacting protein shows 94% identity with mouse Axin, which recently has been identified as a negative regulator of the Wnt signaling pathway; therefore, we termed this protein rAxin (rat Axin). rAxin interacted directly with, and was phosphorylated by, GSK-3beta. rAxin also interacted directly with the armadillo repeats of beta-catenin. The binding site of rAxin for GSK-3beta was distinct from the beta-catenin-binding site, and these three proteins formed a ternary complex. Furthermore, rAxin promoted GSK-3beta-dependent phosphorylation of beta-catenin. These results suggest that rAxin negatively regulates the Wnt signaling pathway by interacting with GSK-3beta and beta-catenin and mediating the signal from GSK-3beta to beta-catenin.

Amino Acid Sequence↗