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Biomedical subjects

H Baba

Publications and source records attributed to H Baba.

At least 55 records · Page 3Linked to original sources

Clinicopathologic and familial characteristics of endometrial carcinoma with multiple primary carcinomas in relation to the loss of protein expression of MSH2 and MLH1.

BACKGROUND: The frequency of synchronous or metachronous multiple primary carcinomas in patients with endometrial carcinoma has been reported to be between 10% and 23% and is highest among all gynecologic carcinomas. However, clinical characteristics and underlying genetic abnormalities in endometrial carcinoma with multiple primary carcinomas has not been well clarified. Endometrial carcinoma is the most commonly associated extracolonic malignancy in hereditary nonpolyposis colorectal carcinoma in which germ line mutations in DNA mismatch repair genes, particularly in MSH2 and MLH1, are known to cause this syndrome. The purpose of the current study was to investigate clinicopathologic and familial characteristics including MSH2, MLH1, and p53 expression in endometrial carcinoma with multiple primary carcinomas, by comparing them to endometrial carcinoma without other primary malignancies. METHODS: Patients were divided into two groups: 30 patients with synchronous or metachronous multiple primary carcinomas other than endometrial carcinoma and 116 patients with endometrial carcinoma without other primary malignancies. Clinicopathologic characteristics, family history of cancer, and immunohistochemical protein expression of MSH2, MLH1, and p53 expression were investigated in both groups, and 15 endometria from benign disease were used for normal controls in immunohistochemistry. RESULTS: The frequency of high risk clinicopathologic factors of endometrial carcinoma and 5-year survival rates and the frequency of p53 overexpression were not statistically different between the two groups. However, the loss of MSH2 and/or MLH1 expression was significant in endometrial carcinoma with multiple primary carcinomas, when compared with endometrial carcinoma alone (22 of 30 vs. 31 of 116). In cases with multiple primary carcinomas, particularly those diagnosed before the patient was 55 years of age or those in which the patient had a family history of cancer, the frequency of this loss was especially high (11 of 13 and 10 of 11, respectively). CONCLUSIONS: The clinical or biologic nature of endometrial carcinoma with multiple primary carcinomas seems to be similar to endometrial carcinoma alone. A high incidence of defective MSH2 and MLH1 protein in endometrial carcinoma with multiple primary carcinomas, however, suggests that abnormalities in the function of MSH2 and MLH1 may play an important role in tumorigenesis for patients with endometrial carcinoma with multiple primary carcinomas and their families.

Adaptor Proteins, Signal Transducing↗

Herniation of cervical intervertebral disc: immunohistochemical examination and measurement of nitric oxide production.

STUDY DESIGN: Surgically obtained cervical herniated intervertebral discs were examined histologically and immunohistochemically. The production of nitric oxide (NO) in the local tissue was examined using the electron spin resonance (ESR) method. OBJECTIVES: To investigate the local histologic and immunohistochemical changes in cervical disc herniation, including NO production, and to compare such changes with those in autopsy cases. SUMMARY OF BACKGROUND DATA: Very little is known about the histopathologic processes of cervical disc herniation. In addition, no information is available on the level of in vivo NO production in cervical disc herniation. METHODS: Thirty-six herniated cervical discs obtained from 31 patients were immunohistochemically examined for localization of blood vessels, matrix metalloproteinase (MMP)-3, and inducible NO synthetase (iNOS). We also compared the production of NO, measured by the ESR method, in eight specimens with that of five control discs obtained from fresh cadavers. RESULTS: The presence of herniated discs correlated with the degeneration of cartilaginous endplate and torn anulus fibrosus. Formation of new blood vessels around the herniated discs was detected, using von Willebrand factor antibody, in seven uncontained hernias and 20 contained hernias. Immunohistochemical studies showed the presence of cells positive for MMP-3 (chondrocytes), iNOS (chondrocytes and granulation tissue) in cervical disc hernias. ESR analysis showed a significantly higher NO production in herniated cervical discs than in disc samples of fresh cadavers. CONCLUSIONS: Herniated cervical intervertebral disc is characterized by the presence of an inflammatory process associated with neovascularization and increased expression of MMP-3. Production of NO was markedly high in both contained- and uncontained-type hernias.

Adult↗

Functional reorganization of sensory pathways in the rat spinal dorsal horn following peripheral nerve injury.

Functional reorganization of sensory pathways in the rat spinal dorsal horn following sciatic nerve transection was examined using spinal cord slices with an attached dorsal root. Slices were obtained from animals whose sciatic nerve had been transected 2-4 weeks previously and compared to sham-operated controls. Whole-cell recordings from substantia gelatinosa neurones in sham-operated rats, to which nociceptive information was preferentially transmitted, revealed that dorsal root stimulation sufficient to activate A afferent fibres evoked a mono- and/or polysynaptic EPSC in 111 of 131 (approximately 85%) neurones. This is in contrast to the response following A fibre stimulation, where monosynaptic EPSCs were observed in 2 of 131 (approximately 2%) neurones and polysynaptic EPSCs were observed in 18 of 131 (approximately 14%) neurones. In sciatic nerve-transected rats, however, a polysynaptic EPSC following stimulation of A afferents was elicited in 30 of 37 (81%) neurones and a monosynaptic EPSC evoked by A afferent stimulation was detected in a subset of neurones (4 of 37, approximately 11%). These observations suggest that, following sciatic nerve transection, large myelinated A afferent fibres establish synaptic contact with interneurones and transmit innocuous information to substantia gelatinosa. This functional reorganization of the sensory circuitry may constitute an underlying mechanism, at least in part, for sensory abnormalities following peripheral nerve injuries.

Afferent Pathways↗

Direct activation of rat spinal dorsal horn neurons by prostaglandin E2.

Whole-cell patch-clamp and intracellular recording techniques have been used to study the action of prostaglandin E2 (PGE2) on neurons in adult rat transverse spinal cord slices. Bath-applied PGE2 (1-20 microm) induced an inward current or membrane depolarization in the majority of deep dorsal horn neurons (laminas III-VI; 83 of 139 cells), but only in a minority of lamina II neurons (6 of 53 cells). PGE2 alone never elicited spontaneous action potentials; however, it did convert subthreshold EPSPs to suprathreshold, leading to action potential generation. PGE2-induced inward currents were unaffected by perfusion with either a Ca(2+)-free/high Mg(2+) (5 mm) solution or tetrodotoxin (1 microm), indicating a direct postsynaptic action. Both 17-phenyl trinor prostaglandin E2 (an EP1 agonist) and sulprostone (an EP3 agonist) had little effect on membrane current, whereas butaprost methyl ester (an EP2 agonist) mimicked the effect of PGE2. Depolarizing responses to PGE2 were associated with a decrease in input resistance, and the amplitude of inward current was decreased as the holding potential was depolarized. PGE2-induced inward currents were reduced by substitution of extracellular Na(+) with N-methyl-d-glucamine and inhibited by flufenamic acid (50-200 microm), which is compatible with activation of a nonselective cation channel. These results suggest that PGE2, acting via an EP2-like receptor, directly depolarizes spinal neurons. Moreover, these findings imply an involvement of spinal cord-generated prostanoids in modulating sensory processing through an alteration in dorsal horn neuronal excitability.

Action Potentials↗

Guide DNA technique reveals that the protein component of bacterial ribonuclease P is a modifier for substrate recognition.

We developed a guide DNA technique with which the cleavage efficiency of pre-tRNA substrate raised in the RNase P reaction. The 20-mer guide DNAs hybridizing to the upstream region of the cleaving site enhanced the cleavage reactions of RNA substrates by Escherichia coli RNase P. This guide DNA technique was also applicable to cleavage site selection by choosing the DNA-hybridizing site. Results showed that RNase P accepts DNA/RNA double-stranded 5'-leader region with high catalytic efficiency as well as single-stranded RNA region in pre-tRNAs as substrates, which suggests that the protein component of bacterial RNase P prefers bulky nucleotides. The protein component did not affect the normal 5'-processing reaction of pre-tRNAs, but enhanced the mis-cleaving (hyperprocessing) reactions of tRNA in non-cloverleaf folding. Our results suggested that the protein component of RNase P is a modifier for substrate recognition.

Bacterial Proteins↗

Essential role of domain 4 of pneumolysin from Streptococcus pneumoniae in cytolytic activity as determined by truncated proteins.

Pneumolysin (PLY), an important virulence factor of Streptococcus pneumoniae, is one of the members of thiol-activated cytolysins (TACYs) consisting of four domains. TACYs commonly bind to membrane cholesterol and oligomerize to form transmembrane pore. We have constructed full-length and various truncated PLYs to study the role of domains of PLY in the cytolytic activity. Full-length PLY had binding ability to both cell membrane and immobilized cholesterol. A truncated PLY which comprised only domain 4 molecule, the C-terminal domain of PLY, sustained the binding ability to cell membrane and cholesterol, whereas domain 1-3 molecule had no binding ability to them. Furthermore, the domain 4 molecule inhibited both the membrane binding and the hemolytic activity of full-length PLY. Accordingly, the present results provided the direct evidence that domain 4 was essential for the initial binding to membrane cholesterol and the interaction led to the subsequent membrane damage process.

Animals↗

Closing-opening wedge osteotomy to correct angular kyphotic deformity by a single posterior approach.

STUDY DESIGN: Seven patients with angular kyphotic deformity of the thoracic or thoracolumbar spine were treated by closing-opening wedge osteotomy using a single posterior approach. OBJECTIVES: To examine the safety and efficacy of closing-opening wedge osteotomy for angular kyphosis. SUMMARY OF BACKGROUND DATA: Correction osteotomy of severe kyphosis is a challenging operation. A two-stage operation has been commonly used: anterior release and decompression followed by posterior correction and fusion. METHODS: Seven patients with angular kyphosis were treated. The apex level of kyphosis was T5 in one patient, T11 in one, and T12 in five. There was old fracture in five patients, congenital deformity in one, and neurofibromatosis in one. The first 30-35 degrees of kyphosis are corrected using the closing wedge technique with the hinge of the anterior longitudinal ligament after veretebrectomy and circumspinal decompression of the spinal cord. Then the hinge is moved posteriorly to the spinal cord and the remainder of the requisit angle of osteotomy is corrected using the opening-wedge technique (closing-opening wedge osteotomy). Spinal curvature is stabilized using posterior instrumentation and graft. RESULTS: Localized kyphosis was reduced from an average of 67 degrees to 18 degrees at 2.2 to 7.5 years' follow-up. Sagittal alignment from T1 to the sacrum became more physiologic than before. There were no neurologic complications. Bony fusion was achieved in all patients, and there was no correction loss. CONCLUSIONS: Satisfactory correction is safely performed by closing-opening wedge osteotomy with a direct visualization of the circumferentially decompressed spinal cord. Although the performance is technically laborious, it offers good correction without jeopardizing the integrity of the spinal cord.

Adult↗

Gait analysis of spastic walking in patients with cervical compressive myelopathy.

To assess neurological status and to evaluate the effect of surgical decompression in patients with cervical myelopathy, we performed computerized gait analysis in 24 patients with cervical compressive myelopathy who showed spastic walking. Gait analysis was repeated during neurological follow-up that averaged 32.4 months. The gait pattern in patients with severe myelopathy was characterized by hyperextension of the knee in the stance phase without plantar flexion of the ankle in the swing phase, significantly reduced walking speed and step length, prolonged stance phase duration and decreased single-stance phase duration, and increased step width. The angle of flexion of the knee joint in the stance phase was significantly correlated with the Japanese Orthopaedic Association (JOA) score. Postoperative neurological improvement was associated with increased walking speed and decreased extension angle of the knee joint (single-stance phase and swing phase). Postoperatively, 12 patients had normalized extension of the knee in stance phase and their walking speed, cadence, stance phase duration, and single-stance phase duration, as well as step length and width, showed nonsignificant differences from these parameters in healthy controls. Our results show that kinesiological gait analysis is clinically useful for the functional assessment of the severity of spastic walking in cervical myelopathy.

Adult↗

Adjuvant chemotherapy for gastric cancer: a comprehensive review.

The role of adjuvant chemotherapy in gastric cancer has been studied extensively over the past three decades in an attempt to further improve the prognosis of patients with gastric cancer who have undergone curative surgery. To date, no definitive conclusions have been drawn from randomized clinical trials of adjuvant chemotherapy for gastric cancer, because few studies have shown a significant positive impact on survival as compared with surgery alone. The negative results of most previous clinical studies do not necessarily mean that the adjuvant chemotherapy approach to treatment of gastric cancer does not work. Recent published reports of meta-analyses concerning adjuvant chemotherapy of gastric cancer revealed small but clear survival advantages for adjuvant therapy over surgery alone. The positive data from meta-analyses suggests that there are potential survival advantages of adjuvant chemotherapy, but this must be proven in the future by well-designed clinical trials that compare adjuvant chemotherapy with surgery alone, in which sufficient numbers of patients are enrolled and effective chemotherapeutic regimens with appropriate dose intensity are employed. Newly developed anticancer agents and/or newer therapeutic combinations or strategies (neoadjuvant chemotherapy, chemoradiotherapy, intraperitoneal chemotherapy) have the potential to benefit high-risk patients.

Antineoplastic Combined Chemotherapy Protocols↗

Remyelination of the adult demyelinated mouse brain by grafted oligodendrocyte progenitors and the effect of B-104 cografts.

The 4e transgenic mouse is characterized by overexpression of the PLP gene. Heterozygous littermates containing three PLP gene copies develop and myelinate normally. However, a progressive CNS demyelination begins at 3-4 months of age. Despite focal demyelination, these animals survive for one year with hind limb paralysis. We used this CNS demyelination model to determine if grafts of CG4 oligodendrocyte progenitors would survive and myelinate the adult CNS. Either CG4 cells, or co-grafts of CG4/B 104 cells 11:1 ratio respectively) were performed. Grafted cells survived and migrated in the normal and transgenic brain. Non-treated transgenic animals revealed extensive lack of myelin. Three months post-transplant hosts with CG4 or co-transplants displayed a near normal myelin pattern. Double immunofluorescence for neurofilament and myelin basic protein revealed the presence of many naked axons in non-grafted transgenic animals. Those grafted with progenitor CG4 cells or cografts displayed a clear increase in remyelination. This data provides a new direction for the development of cell replacement therapies in demyelinating diseases.

Animals↗

In vivo kinematic analysis of total knee arthroplasty with four different polyethylene designs.

The femorotibial contact point on the sagittal plane was measured under weight-bearing conditions in 45 subjects with implanted and nonimplanted knees. They consisted of 11 knees with flat bearing inserts, 16 knees with shallow dished inserts, 10 knees with posterior lipped inserts, 10 knees with posterior stabilized bearing inserts, and 8 normal knees selected as controls. The average amount of anterior translation of the knee with a flat bearing insert was significantly larger than that of the other implanted knees. The average femorotibial contact point did not differ significantly among knees with shallow dished, posterior lipped, and posterior stabilized bearing inserts, but posterior stabilized knees exhibited most frequently a normal posterior movement. Based on our results, it may be safer to use more anteroposterior constrained bearing inserts in total knee arthroplasty, particularly when the posterior cruciate ligament is loose.

Aged↗

Relationships among bone mineral densities, static alignment and dynamic load in patients with medial compartment knee osteoarthritis.

OBJECTIVE: To investigate the relationships among bone mineral density (BMD), static alignment and the adduction moment of the knee in patients with tibiofemoral osteoarthritis (OA). METHODS: Sixty-nine patients with medial compartment knee OA underwent radiographic evaluation, gait analysis and BMD measurements at the proximal tibia and lumbar spine. RESULTS: The bone mineral distribution of the medial to lateral part of the proximal tibia correlated significantly with the peak knee adduction moment and the mechanical axis. Furthermore, the adduction moment correlated significantly with the mechanical axis. However, the BMD of the lumbar spine and the bone mineral distribution of the posterior to anterior part of the proximal tibia did not correlate with any other measurement. CONCLUSIONS: Our results suggest that the bone mineral distribution of the proximal tibia is directly affected but lumbar BMD is not influenced by the local mechanical stress around the knee with medial compartment OA.

Absorptiometry, Photon↗

The placement of the epidural catheter at the predicted site by electrical stimulation test.

UNLABELLED: More accurate segmental and sagittal positioning of the epidural catheter tip is required for the success of continuous epidural analgesia, spinal cord monitoring, and percutaneous epidural spinal cord stimulation. We examined the usefulness of an electrical stimulation test for verifying the proper placement of the epidural catheter tip at the predicted site in the posterior epidural space by using a locally developed epidural catheter with electrodes at its tip. The test included the observation of segmental bilateral muscle twitches and the patient's report of feeling in the region stimulated by moving the epidural catheter electrode back and forth and changing the direction of the bevel of the Tuohy needle. The success rate of midline placement at the required spinal segment was significantly more frequent (99%; P < 0.001) in the group (n = 289) receiving the electrical stimulation test compared with the group (n = 277) not receiving the test (success rate 57%). The results indicate the usefulness of this method. We concluded that the electrical stimulation test is effective for verifying the proper placement of the catheter electrode tip. IMPLICATIONS: Ideally the epidural catheter tip should be positioned in the posterior epidural space near the midline. We concluded that the electrical stimulation test is effective for verifying the proper placement of the catheter electrode tip.

Aged↗

Coaggregation of Porphyromonas gingivalis and Prevotella intermedia.

Porphyromonas gingivalis cells coaggregated with Prevotella intermedia cells. The coaggregation was inhibited with L-arginine, L-lysine, Nalpha-p-tosyl-L-lysine chloromethyl ketone, trypsin inhibitor, and leupeptin. Heat- and proteinase K-treated P. gingivalis cells showed no coaggregation with P. intermedia cells, whereas heat and proteinase K treatments of P. intermedia cells did not affect the coaggregation. The vesicles from P. gingivalis culture supernatant aggregated with P. intermedia cells, and this aggregation was also inhibited by addition of L-arginine or L-lysine and by heat treatment of the vesicles. The rgpA rgpB, rgpA kgp, rgpA rgpB kgp, and rgpA kgp hagA mutants of P. gingivalis did not coaggregate with P. intermedia. On the other hand, the fimA mutant lacking the FimA fimbriae showed coaggregation with P. intermedia as well as the wild type parent. These results strongly imply that a heat-labile and proteinous factor on the cell surface of P gingivalis, most likely the gingipain-adhesin complex, is involved in coaggregation of P. gingivalis and P. intermedia.

Adhesins, Bacterial↗

Tumor growth patterns and biological characteristics of early gastric carcinoma.

Gastric cancer is a major malignant disease. The development of new diagnostic techniques and mass screening have led to increased detection rates of patients with early-stage gastric cancer in Japan. However, after curative resection of early gastric cancer, there are various types of recurrences, and residual occult disease and distant micrometastasis precede death. The growth and metastatic potential of cancer cells are closely related to the postoperative outcome, and patients at risk for cancer-related death after surgery have to be closely monitored to prevent tumor recurrence. The biological behavior of cancer cells should be determined in patients with early gastric cancer and with a less favorable prognosis to detect potential early recurrences in the liver. Two types of growth patterns have been found in early gastric cancer: the superficially spreading (Super) type and the penetrating (Pen) type, and the clinicopathological and biological characteristics of each type have been extensively determined. A subtype of the Pen-type gastric cancer, which is progressing expansively with complete destruction of the muscularis mucosae (Pen A type) has a less favorable prognosis due to early recurrences in the liver. These clinical cancer types are closely related to chromosomal instability in DNA aneuploidy and p53 overexpression, and vascular endothelial growth factor activation induced tumor angiogenesis, vascular invasion and hematogenous metastasis. Thus, patients with Pen-A-type cancer showing expansive tumor growth had a poorer postoperative outcome and a hematogenous-related recurrence of the cancer. Antiangiogenic approaches in a postoperative setting may prove to be effective in preventing tumor recurrence and improving the prognosis for these patients.

Adenocarcinoma↗

Expression and localization of lumican in the ischemic and reperfused rat heart.

Lumican belongs to the small leucine-rich proteoglycan family and has an important role in the regulation of corneal and dermal collagen fiber assembly. Recently, lumican mRNA was found in the heart and its high expression was reported during wound healing of the cornea. In the present study, the expression and role of lumican in fibrosis of an ischemic and reperfused rat heart were examined. The expression level of lumican mRNA increased in the ischemic and reperfused rat heart and was highest on the fourth week. Lumican protein existed in the forms of core protein and proteoglycan in the control rat heart. The amount of lumican in the form of proteoglycan increased, and that as the form glycoprotein was newly detected in the ischemic and reperfused rat heart on the fourth week. In the control heart, lumican was weakly expressed in the collagen fibers of the perivascular area, but it was expressed strongly in many capillary endothelial cells in the ischemic lesion on day 1. After 3 days, lumican was localized in collagen fibers and in the fibroblasts of fibrotic lesions. A few myocardial cells close to the ischemic lesion expressed lumican mRNA. Lumican is considered to play an important role in the fibrillogenesis of the ischemic and reperfused rat heart.

Animals↗

Rapid degradation of the silkworm diapause hormone by trypsin and its suppression by VAP-map, a synthetic analog of the cuticular peptide of silkworm, Bm ACP-6.7 (VAP-peptide).

Very fast tryptic degradation of the silkworm diapause hormone was found and the degradation pathway was analyzed by moderating the reaction conditions. It proceeded via cleavage at Arg23 and finally at Arg15 of DH. As the C-terminal structure of DH was essential for exhibiting bioactivity, the first cleavage caused rapid inactivation of the hormone. This tryptic digestion was strongly suppressed by adding VAP-map, a synthetic analog of the cuticular peptide of silkmoths, Bm ACP-6.7 (VAP-peptide), which is a natural synergist of DH. VAP-map suppressed the enzymic reaction by interacting with the substrate, but not with the enzyme.

Amino Acid Sequence↗