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Biomedical subjects

H Baba

Publications and source records attributed to H Baba.

At least 37 records · Page 2Linked to original sources

Use of osteonics UHR hemiarthroplasty for fractures of the femoral neck.

A clinical and radiographic study of bipolar hip arthroplasties was performed for fractures of the femoral neck. All patients were treated with the Osteonics UHR system. Clinical results were evaluated in 77 patients (77 hips) who were observed for an average of 4.8 years (range, 2-10 years). At the latest followup, 67 (87%) patients were rated as having a good or excellent outcome according to the Hospital for Special Surgery hip rating system. Clinical ratings in patients treated with cementless UHR were similar to or better than those of patients with cemented UHR. Hip dislocation occurred in only 3 (2.3%) patients, in whom the hip joint was reduced by a closed procedure without inducing disassembly of the prosthetic components. None of the patients had definitive acetabular erosion. The motion of the outer head was evaluated radiographically in 63 patients in weightbearing and non-weightbearing conditions, 3 to 108 months after surgery. The relative motion at the 2 sites of articulation of the outer head had stabilized by 3 months after surgery and subsequently remained unchanged. The authors' findings indicate that UHR hemiarthroplasty of the femoral head is a reliable treatment for fractures of the femoral neck.

Activities of Daily Living

GFAP gene expression during development of astrocyte.

Glial fibrillary acidic protein (GFAP) is expressed exclusively in astrocytes in the central nervous system. In order to characterize individual cultured cells in which the GFAP promoter is active and to identify the regulatory mechanisms of GFAP expression in these cells, we have developed a unique assay system for promoter activity using retrovirus vectors. Retrovirus containing the mouse GFAP promoter fused to the lacZ gene were used to infect mixed glial cultures. The infected cells, in which the GFAP promoter was active, were visualized by X-Gal staining. From these experiments, we found that a 256 bp fragment 5' of the transcription initiation site was sufficient to confer astrocyte-specific expression of GFAP. The GFAP promoter became active about 3 days before GFAP protein can be detected immunohistochemically, which indicates that detection of GFAP promoter activity can be used to identify astrocyte progenitors. We have also established immortalized astrocyte cell lines in which we detect GFAP promoter activity. Immorto mouse is a transgenic mouse generated by the introduction of thermolabile SV40 T Ag, tsA58. A mixed glial culture prepared from 2-day-old Immorto mouse brain was incubated at 32 degrees C, at which temperature most of the cells expressed T Ag. The culture was then infected with retrovirus containing GFAP promoter-lacZ, and the infected cells were selected. Using the fluorescence-activated cell sorter with fluorescein di-beta-D-galactopyranoside as a substrate (FDG-FACS), these cells were separated into two groups: FDG(+), in which the GFAP promoter was active, and FDG(-), in which it was inactive. Mature astrocyte cell lines were established from the FDG(+) cells by colony isolation. The FDG(-) cells were cloned by colony isolation and cultured at 32 or 39 degrees C. At the latter temperature the expression of T Ag was suppressed and cell differentiation was induced in most cells. The cells which became positive for X-Gal staining only after switching to 39 degrees C were collected as immature astrocyte cell lines. These immortalized cell lines should be useful to investigate the molecular mechanisms of astrocyte differentiation.

Animals

Astrocytic lineage analysis by detection of GFAP promoter activity in vitro.

To survey the emergence and onset of differentiation of the astrocytic lineage in the developing mouse cerebral wall, the promoter activity of a 2.5 kb 5'-flanking region of glial fibrillary acidic protein (GFAP) was measured in individual developing brain cells using a retrovirus-mediated gene transfer system. We identified precursors for astrocytes in primary culture of embryonic mouse cerebral wall cells by detection of GFAP promoter activity, which was detected approximately 3 days prior to the appearance of GFAP immunoreactivity. Since retroviruses only integrate into the chromosomes of actively proliferating cells, cells detected by this method should have been mitotically active at the time of retroviral infection on day 15 postfertilization (E15). Furthermore, we observed that cells activating GFAP promoter were located near the ventricular surface of cultured cerebral wall slices as a cluster of spherical cells. These results demonstrate that precursor cells for astrocytes exist within the germinative zone of developing cerebral wall, and that these cells are mitotically active on day E15, which is a late stage of neuronal production period in the mouse cerebral wall. The morphology, location and mitotic activity of these cells suggest that they are unlikely to be cells that have been transformed from radial glial cells.

Animals

[The causes and management of ischemic mitral regurgitation].

Ischemic mitral regurgitation (IMR) is recognized as one of the complications of coronary artery disease. The aim of this study is to evaluate the causes and surgical management of IMR. From October 1986 to March 1995, 443 of patients underwent isolated coronary artery bypass grafting (CABG). In forty-four of the patients (9.9%) who underwent isolated CABG, the severity of postoperative IMR was reduced by two or more grades by the Sellers index. Hemodynamic parameters of these patients included: left ventricle ejection fraction, left ventricle end-diastolic volume index and left ventricle regional wall motion. They were assessed by left ventriculography (LVG). In addition, cardiac index and pulmonary artery wedge pressure were assessed by S-G catheterization and mitral annulus diameter by ultrasonic echocardiography. Twenty-nine patients experienced an increase in IMR severity after CABG, one of whom required mitral valve replacement for cardiac failure, and later died due to low output syndrome postoperative. On the other hand, fifteen patients experience a reduction in IMR severity after CABG. We conclude that the causes of IMR were regional asynergy at the site of papillary muscle, mitral annulus dilation and left ventricle dilation. Our findings suggest that severe IMR patients required concomitant mitral valve surgery with CABG. Patients with mild or moderate IMR patients with mitral annulus dilation or regional asynergy at the site of mitral papillary muscle may require the same surgery.

Coronary Artery Bypass

[Pyrimidine nucleoside phosphorylase activity, 5-fluorouracil concentration and thymidylate synthase inhibition rate in colorectal cancer after oral administration of 5'-doxifluridine].

To assess the mechanism of the anticancer effect of doxifluridine (5'-DFUR), a clinicopharmacological study was performed. So far, no comparative study has been reported between the thymidylate synthase (TS) inhibition rate and the 5-FU concentration in colorectal cancer after oral administration of 5'-DFUR. In 37 patients with colorectal cancer, 5'-DFUR was administered orally/preoperatively (800 mg/day x more than 4 days before operation and 300 mg on the day of operation). The mean total dosage was 6.9 g. Specimens of tumor and normal intestinal tissue were obtained 4.4 hours on average after final administration. The TS inhibition rate as well as the 5-FU concentration and the activity of pyrimidine nucleoside phosphorylase (PyNPase) were analyzed in both tissues. The PyNPase activity was significantly higher in the tumor tissue than in the normal tissue (137.9 +/- 10.8 vs. 31.0 +/- 4.7 micrograms FU/mg protein/hr, p < 0.0001). The 5-FU concentration was also significantly higher in the tumor tissue than in the normal tissue (101.3 +/- 30.6 vs. 23.2 +/- 5.5 ng/g, p = 0.024). The TS inhibition rate correlated with the 5-FU concentration in the tumor tissue (r = 0.527, p = 0.047). These findings suggest that the TS inhibition rate may be an index of the anticancer effect of 5'-DFUR in colorectal cancer.

Adenocarcinoma

Scientific basis for the combination of tegafur with uracil.

Fujii et al reported that Uracil potentiated the antitumor activity of fluorouracil (5-FU) and 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur). This effect was due to inhibition of the degradation of 5-FU, yet the phosphorylation of 5-FU was unaffected. The molar ratio of tegafur and uracil was 1:4, a combination that has since been widely prescribed in Japan for the treatment of cancer patients. We present here our experimental and clinical results when investigating the antineoplastic effects of this combination of drugs--known as UFT--and provide evidence that UFT is an effective treatment for patients with cancer.

Chemotherapy, Adjuvant

Potential role of streptozotocin in enhancing ossification of the posterior longitudinal ligament of the cervical spine in the hereditary spinal hyperostotic mouse (twy/twy).

We investigated the effects of streptozotocin-induced diabetes mellitus on ossification of the posterior longitudinal ligament (OPLL) in the murine cervical spine. A genetically-bound spinal hyperostotic mouse, the tip-toe walking Yoshimura (twy) mouse, was used in these experiments. Histological examination showed that streptozotocin enhanced membranous and enchondral ossification of the posterior longitudinal ligament of the cervical spine, particularly in the area of the ligamentous enthesis. It also increased the number of alkaline phosphatase-positive osteoblast-like mesenchymal cells particularly around the enthesis, while the number of such cells was less in control twy mice and ICR mice treated with streptozotocin. The area of OPLL subsequently increased in size in streptozotocin-treated twy mice. We suggest that streptozotocin-induced diabetes enhances OPLL in the genetically-bound spinal hyperostotic mouse (twy/twy).

Age Factors

Enhanced aggregation of beta-amyloid-containing peptides by extracellular matrix and their degradation by the 68 kDa serine protease prepared from human brain.

To explore whether extracellular matrix components in human brain affect the deposition and aggregation of beta-amyloid containing peptides, human brain samples from patients with sporadic Alzheimer's disease and normal aged were analyzed by Western blot analysis. All major beta-amyloid-containing peptides contained epitope(s) which is recognized by anti heparan sulfate antibody. Incubation of brain beta-amyloid-containing peptides with human collagen type IV in neutral pH efficiently generated a high molecular weight aggregated band, approximately 5-fold that of the control sample. We have previously found a serine protease which is capable of cleaving an oligopeptide at the N-terminus of beta-amyloid. In this study, the protease, which also contains heparan sulfate glycoconjugates, degraded the above brain peptides as natural substrates, although with different efficiency. These findings suggest that extra-cellular matrix components affect the processing and aggregation of beta-amyloid-containing peptides in human brain.

Aged

Independent and differential expression of two isotypes of human Nm23: analysis of the promoter regions of the nm23-H1 and H2 genes.

We isolated genomic clones of two isotypes of human NDP kinase, nm23-H1 and H2. The nm23-H1 and H2 genes located in a tandem array contained 5 exons and most of the splicing sites in the exon-intron junctions of two isotypes were essentially identical. The regulatory elements of nm23-H1 and H2 genes were also analysed. One major and several minor transcriptional initiation sites were detected in the two isotypes by 5' RACE analysis in HeLa cell. We also identified them by means of an RNase protection assay and primer extension analysis. Promoter activities were found in the 5' flanking sequences of the two genes when placed upstream of the chloramphenicol acetyltransferase gene. Transcriptional activities of nm23-H1 and H2 regulatory regions were measured in a series of human cancer lines. The nm23-H1/nm23-H2 gene transcriptional activity ratio varied depending on the cell line. DNA sequencing of these two genes showed that their promoter regions contain distinct binding sites for known transcriptional factors. These studies suggest that the two isotypes of the nm23 genes might be regulated dissimilarly, and in cell type specific manner.

Base Sequence

Human brain beta-secretase contains heparan sulfate glycoconjugates.

A polyclonal antibody against the 68 kDa beta-secretase was established, which recognizes a single 68 kDa band in brain homogenate of Alzheimer's disease patients and normal aged. Western analysis revealed that the protease is an acidic glycoprotein with negative charge on its glycoconjugate(s). Sensitiveness to heparitinase and glycopeptidase A indicates that the protease contains asparagine-linked oligosaccharide with heparan sulfate moieties. Specific detection of the 68 kDa band in the analysis using anti-heparan sulfate antibody, and its time-course-dependent degradation, also confirm the above results. It seems that, like human blood coagulation factors IXa and XIa, the glycoconjugate(s) attached to the protease interfere with substrate specificity, stability and topological restriction of proteolysis in brain extracellular matrix, where diffuse plaque formation is taking place.

Aged

Cadaveric vascular anatomy for total en bloc spondylectomy in malignant vertebral tumors.

STUDY DESIGN: The authors studied the vascular anatomy of the thoracic and lumbar spine in cadavers related to the clinical use of total en bloc spondylectomy in malignant vertebral tumors. OBJECTIVE: To enhance anatomic knowledge on major and associated segmental vessels surrounding the anterior vertebral column of the thoracic and lumbar spine. SUMMARY OF BACKGROUND DATA: No reports have, to the authors' knowledge, referred clinically to the anatomic relationship between the vascular system and the anterior vertebral column in performing posterior total en bloc spondylectomy on the thoracic and lumbar spine. METHODS: The authors studied the major vessels, segmental arteries and veins, and tendinous portions of the lumbar diaphragm inserting onto the vertebrae in 21 cadavers to view the vascular system surrounding the anterior vertebral column in the thoracic and lumbar spine. RESULTS: The aorta descended in direct contact with the anterior vertebral column below T4 or T5 and branched into two common iliac arteries at L3 in one cadaver, at L3-L4 in two, at L4 in eight, at L4-L5 in nine, and at L5 in one. The uppermost intercostal artery originated at T4 or T5, and 48 (14%) variations in 348 intercostal arteries did not originate from the thoracic aorta. Two common iliac veins became confluent at L3-L4 in one subject, at L4-L5 in 13, and at L5 in seven. The inferior vena cava ascended in tight contact with the vertebral column and entered into the vena caval foramen of the diaphragm anterior to the right medial crus. The right medial crus of the diaphragm originated from the vertebra at L1-L2 in one subject, at L2 in two, at L2-L3 in 14, and at L3-L4 in four, whereas, on the left, this ligamentous origin located at L1-L2 in six, at L2 in two, at L2-L3 in 11, and at L3-L4 in two. The first two lumbar arteries ran consistently in the space between the medial crus and the vertebral column. CONCLUSIONS: Total en bloc spondylectomy conducted posteriorly is less likely to damage the thoracic aorta from T1 to T4 but, distal to T5, the aorta must be carefully retracted anteriorly before manipulation of the affected vertebra(e). For a malignant tumor involving L1 or L2, the medial and, occasionally, the intermediate crura of the diaphragm and the first two lumbar arteries must be treated carefully before spondylectomy. Malignant tumors involving the L3 and L4 vertebral bodies can be approached with a total en bloc spondylectomy technique only when the inferior vena cava has been safely retracted anteriorly.

Aged

Laminoplasty with foraminotomy for coexisting cervical myelopathy and unilateral radiculopathy: a preliminary report.

STUDY DESIGN: An assessment was made of the efficacy of a combined laminoplasty and foraminotomy operation for patients with coexisting myelopathy and unilateral radiculopathy. The procedure was done in 17 patients. OBJECTIVES: The patients were followed with lateral flexion and extension radiographs, computed tomography scans, and an assessment system specially designed to qualitatively evaluate the patients' neurologic status. Follow-up period averaged 4 years (range, 2.1-9.3 years). SUMMARY OF BACKGROUND DATA: Excellent-to-good results were obtained for 76% (13 of 17) of the patients without any significant functional compromise based on the radiographs. Sixteen nerve roots were decompressed with a less than 25% foraminotomy, whereas eight were decompressed by a 25%-50% foraminotomy without serious neurologic damage, except for one patient. The neurologic results appeared unrelated to the extent of foraminotomy. METHODS: A refined procedure for combined laminoplasty and foraminotomy was reviewed retrospectively in terms of neurologic outcome and radiographic data. RESULTS: The present series is small, and results are not comparable directly with other methods. The procedure appears effective for myelopathy and radiculopathy. This procedure is applicable to patients with myelopathy and coexisting nerve root impingement anterolaterally or in the neural foramen. CONCLUSION: The combined laminoplasty and foraminotomy operation may provide greater neurologic improvement in patients with coexisting myelopathy and unilateral radiculopathy, while maintaining cervical spine stability after surgery.

Adult

Clinical manifestations in patients with hereditary nonpolyposis colorectal cancer.

The clinical manifestations of 1,042 Japanese patients with nonpolyposis colorectal cancer who underwent a resection between 1972 and 1992 at the National Kyushu Cancer Center were examined. Hereditary nonpolyposis colorectal cancer (HNPCC) was found in 39 (3.7%) patients. Some characteristic findings in HNPCC cases included early age of onset, a preponderance of right colon cancers, an increased frequency of colorectal cancers, and a favorable survival. Metachronous (postoperative) colorectal cancers developed significantly more often in cases with HNPCC than in those without (12.8% vs. 1.8%, P = 0.0001). Metachronous (postoperative) extracolonic cancers tended to develop more often in cases with HNPCC than in those without (10.2% vs. 3.5%, P = 0.053). In cases with HNPCC, the mean interval between the initial surgery and the diagnosis of the second cancer was 61 months (range; 12-153 months). These findings thus indicate the importance of routine and long-term follow-up to identify any second lesions, especially in patients with HNPCC.

Adolescent

Lordotic alignment and posterior migration of the spinal cord following en bloc open-door laminoplasty for cervical myelopathy: a magnetic resonance imaging study.

We investigated lordotic alignment and posterior migration of the spinal cord following en bloc open-door laminoplasty for cervical myelopathy. Fifty-five patients (32 men and 23 women) were studied, with an average follow-up of 2.4 years. Radiological examination included evaluation of lordosis of the cervical spine and spinal cord, degree of enlargement of bony spinal canal, and the magnitude of posterior cord migration. We also correlated these changes with neurological improvement. Postoperatively, there was an average of 5% loss of cervical spine lordosis (P > 0.01) on radiographs and 12% reduction in the lordotic alignment of the spinal cord (P > 0.05) on magnetic resonance imaging. Postoperatively, the size of the bony spinal canal increased by 48%. Posterior cord migration showed a significant correlation with the preoperative cervical spine and spinal cord lordosis (P < 0.05). Thirty-seven (67%) patients with neurological improvement exceeding 50% showed significant posterior cord migration following laminoplasty compared with those demonstrating less than 50% improvement (P = 0.01). Our results suggest that a significant neurological improvement is associated with posterior cord migration after cervical laminoplasty.

Adult

Quantitative analysis of the spinal cord motoneuron under chronic compression: an experimental observation in the mouse.

We investigated quantitative changes in spinal cord motoneurons following chronic compression using a mouse model of cervical cord compression. Twenty-five tip-toe-walking Yoshimura (twy) mice with calcified mass lesions compressing the spinal cord posterolaterally at the C1-C2 vertebral levels were compared with five Institute of Cancer Research (ICR) mice that served as controls. Spinal cord motoneurons in the anterior grey horn between the C1 and C3 spinal cord segments were Nissl-stained and counted topographically and then analysed in relation to the extent of spinal cord compression. The number of motoneurons in C1-C3 spinal cord segments decreased significantly with a linear correlation with the transverse area of the spinal cord when the cord was compressed to 50-70% of control values. A significant reduction in the number of motoneurons occurred at the C2-C3 spinal cord segment compressed at the C1-C2 vertebral level. In contrast, at the level rostral to the C1 vertebra, the number of motoneurons increased significantly in proportion to the magnitude of compression. The current study demonstrates that a number of neurons, morphologically consistent with anterior horn cells, were observed at a rostral site absolutely free of external compression where no such cells normally exist.

Animals

Lumbosacral dumb-bell neurilemmoma approached by microsurgical interlaminar foraminotomy. A case report.

The case history of a patient with a dumb-bell neurilemmoma arising from the L5 nerve root is described. The tumour extended into the outlet of the neural foramen at L5-S1 on the left and was also compressing the dural sac and the S1 nerve root. A limited laminotomy at L4-5 and L5-S1, with preservation of the neural arch, was followed by microsurgical medial foraminotomy at L5-S1 which allowed visualisation of the nerve root and enucleation of the tumour. The technique maintains stability of the posterior elements and spinal movement, and is recommended for the removal of this type of tumour.

Adult

Flavone acetic acid increases the cytotoxicity of mitomycin C when combined with hyperthermia.

Flavone acetic acid (FAA, NSC 347512) is known to selectively reduce tumor blood flow. Taking advantage of this pharmacodynamic effect, we have previously shown that FAA in combination with hyperthermia (HT) can produce a marked improvement in antitumor response in mice. In the present study, we investigated whether FAA could increase the cytotoxicity of mitomycin C (MMC), a bioreductive drug with selective cytotoxicity against hypoxic cells, under either normothermic or hyperthermic conditions. In vitro, the cytotoxicity of MMC against B16 melanoma cells was not enhanced with exposure to FAA at concentrations less than 100 microgram/ml, even when combined with HT (43 degrees C, 60 min). The cytotoxicity of MMC (1 microgram/ml) at pH 6.5, however, was enhanced by exposure of cells to hypoxia in combination with HT. In vivo, the tumor growth time, calculated as the time required to double the initial tumor volume, was 5.2, 6.8, 8.5, and 15.0 days with FAA (150 mg/kg) alone, MMC (4 mg/kg) alone, FAA + MMC, or FAA + MMC + HT (43 degrees C, 15 min) treatment groups, respectively. Antitumor response obtained in animals treated with FAA plus MMC with HT was clearly better than that obtained in any of the other groups. Scheduling of FAA, MMC, and HT was found to be important in producing optimal antitumor response. Administration of MMC (4 mg/kg) prior to FAA (150 mg/kg) and subsequent HT treatment was superior to administration of FAA before MMC. In an attempt to explain these findings, the influence of FAA on blood flow in skeletal muscle and in tumor was examined using a laser blood flowmeter. FAA administration to mice produced a 75% reduction in blood flow to the tumor for up to 2 h but had no detectable effect on normal skeletal blood flow. Our current explanation of the increased antitumor response achieved with the combination of MMC, FAA, and HT is as follows. The FAA-mediated decrease in blood flow to the tumor, when combined with HT, may produce sufficiently hypoxic conditions to significantly increase the antitumor efficacy of the bioreductive drug, MMC. We believe that clinical testing of this combined drug treatment with hyperthermia is warranted.

Animals

Spinal tracts producing slow components of spinal cord potentials evoked by descending volleys in man.

Slow negative (N) and slow positive (P) waves are frequently produced in the posterior epidural space at the lumbosacral enlargement by epidural stimulation of the rostral part of human spinal cord. The production of these slow potentials are thought to be responsible for analgesia at the stimulated segment as well as below that level. In order to define the spinal tract which mediates these slow potentials, we stimulated directly or from the epidural space the dorsal, dorsolateral, lateral and ventral columns at the cervical or thoracic level, and epidurally recorded spinal cord potentials (des.SCPs) at the lumbosacral enlargement in 7 patients who underwent spine or spinal cord surgery. The des.SCPs recorded in the lumbosacral enlargement consisted of polyphasic spike potentials followed by slow N and P waves. At a near threshold level of stimulus intensity the slow N and P potentials were consistently elicited only by stimulation of the dorsal column. The slow waves were also produced by intense stimulation of other tracts, but remained significantly (P < 0.05 - P < 0.01) smaller than those evoked by dorsal column stimulation when compared at the same stimulus intensity. Moreover, the slow P wave could not be elicited even by intense stimulation (10 times the threshold strength for the initial spike potentials) of the ventral column. Thus, the results suggest that the slow N and P waves are mostly mediated by the antidromic impulses descending through the dorsal column.

Adult