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Biomedical subjects

M Ishiguro

Publications and source records attributed to M Ishiguro.

At least 91 records · Page 5Linked to original sources

[Japanese cases of hyperostosis frontalis interna].

Although hyperostosis frontalis interna is common in the western countries, it has been rarely reported in the literature in Japan. We had a chance to observe 5 cases diagnosed as hyperostosis frontalis interna. They were found among 10,902 patients who came to our hospital from August 1, 1993 to September 30, 1995. All the patients in these five cases are females aged 67 to 85 (mean = 74.2 years). Four of the 5 cases had been treated as hypertension, 2 as diabetes mellitus, and 1 as hyperlipoidemia. Two cases were accompanied by unruptured aneurysms. The pathology of one case accompanied by chronic subdural hematoma revealed no apparent development of Haversian systems of bone. It seems that the prevalence of this disease in Japan would increase from now on due to the fact that the life style and the diet among Japanese people has been getting westernized.

Age Factors↗

Epithelioid sarcoma with an 18q aberration.

Epithelioid sarcoma is a peculiar soft-tissue neoplasm of uncertain origin, which is characterized by an epithelioid morphology of tumor cells coexpressing epithelial (keratin) and nonepithelial (vimentin) antigens. We herein report a new cytogenetic abnormality with der(22)t(18;22)(q11;p11.2) in a case of epithelioid sarcoma that occurred in the elbow of a 75-year-old man. Histologically, the tumor demonstrated a multinodular proliferation of epithelioid cells, with positive immunostaining for keratin, epithelial membrane antigen (EMA), and vimentin. Cultured tumor cells obtained from fresh surgical materials were frozen in plastic ampules and stocked in a liquid nitrogen freezer. Six years after surgery, the cells were recovered from the freezer and utilized for both morphologic and cytogenetic analyses. These cultured cells both before and after the freezing exhibited essentially the same epithelioid morphology and immunophenotypes as those of the original tumor. A chromosome analysis, together with fluorescence in situ hybridization (FISH), demonstrated a 61-67 modal population, and a characteristic clonal abnormality with der(22)t(18;22)(q11;p11.2). Other clonal abnormalities included numerical (-3, -4, +7, -13, -14, -16, -18, +20, -22) and structural (8p+, 9p+, 12p+, i(21q)) aberrations. Some variant clones also demonstrated i(18q). Since the breakpoint at 18q11 is similar to that reported in synovial sarcoma, this finding may support the presence of a histogenetic relationship between epithelioid sarcoma and synovial sarcoma. Our study thus indicates that the storage of frozen cells is useful for both morphologic and cytogenetic analyses of soft tissue tumors.

Aged↗

Modeling study on a hydrolytic mechanism of class A beta-lactamases.

Comparison of the hydrogen-bond networks at the active site in the crystallographic structures reported for class A beta-lactamases revealed an importance of a switch of the hydrogen-bond network for the catalytic process. Taking account of the conformational mobility of the Lys73 residue, we have constructed putative complex models for beta-lactam antibiotics and the enzymes in the multistep hydrolysis which consists of a Michaelis complex, an acyl-enzyme, and a tetrahedral oxyanion for deacylation. In the acylation, the C3 carboxylate of penicillin derivatives would participate in activation of the Ser130 hydroxyl group and then the oxyanion of the Ser130 residue would deprotonate the ammonium group of the Lys73 residue which will act as a general base for activation of the Ser70 residue. In the deacylation, the deacylating water molecule would be accommodated during a conformational change of the acyl moiety without a structural change of the active-site residues and the unprotonated N4 atom of the penicillins would act as a general base to activate the water molecule. This catalytic process provided a new account for the stability of the acyl-enzyme complexes. This substrate-assisted mechanism would also be extended to a hydrolytic mechanism of class C enzymes.

Amino Acid Sequence↗

Color Center Laser-Microwave Double Resonance Spectroscopy of the nu1 Vibrational State of HCCF

Rotational transitions of fluoroacetylene in the nu1 (CH stretch) vibrational state have been observed by the laser-microwave double resonance technique using a color center laser as a radiation source in the 3 μm region. The rotational constant and centrifugal distortion constant in the nu1 state were determined to be 9684.310(16) MHz and 2.68(62) kHz, respectively, where the uncertainties given in parentheses correspond to 2.5 standard deviations.

Journal Article↗

Short arm of chromosome 1 aberration recurrently found in pigmented villonodular synovitis.

Pigmented villonodular synovitis (PVNS) is a relatively uncommon benign lesion that is characterized by diffuse synovial proliferation, mainly occurring in knee joints. Cytogenetic reports about this lesion are few and they describe the presence of numerical and structural chromosome aberrations. We obtained PVNS tissue from the left knee joint of a 53-year-old female, and performed cytogenetic analysis. Fluorescence in situ hybridization (FISH) was also performed by using the formalin fixed, paraffin embedded PVNS tissue. Two seemingly unrelated clones were found: the first clone had structural abnormalities of chromosome 1, 3, and 18, and the second one had trisomy 7 as a sole numerical abnormality. FISH using a chromosome 7 specific alpha-satellite DNA probe revealed that interphase nuclei possessed two or three signals. We describe the clonal aberrations found in a case of PVNS. The deleted lesion of the chromosome 1 (1p10-1p31.3) includes the locus of coagulation factor III gene (1p22-p21), and the coagulation factor V (1q21-q25) locus includes another breakpoint that is 1q25. In addition, recurrent structural abnormalities at the short arm of chromosome 1 have been reported. These facts might play some role in the hemorrhagic tendency and histogenesis of these lesions.

Chromosome Aberrations↗

Pathogenesis of hyponatremia following subarachnoid hemorrhage due to ruptured cerebral aneurysm.

BACKGROUND: Hyponatremia following subarachnoid hemorrhage (SAH) occurs due to the inappropriate secretion of antidiuretic hormone (SIADH). However, this condition is also sometimes associated with certain dehydration states. METHODS: To clarify the pathogenesis, daily values of urine volume, water balance, and sodium balance (Na Bal) were correlated with plasma levels of atrial natriuretic peptide (ANP), antidiuretic hormone (ADH), and plasma renin activity (PRA) in 31 cases of SAH. RESULTS: Na Bal was markedly negative on days 2 and 3. Cumulative Na Bal showed continuous negative values until day 10 following SAH. ANP values showed a consistent elevation, while ADH showed only an initial surge. PRA, as the gross indicator of circulatory volume, showed a lack of suppression, indicating no increase in the circulatory volume. CONCLUSION: Hyponatremia following SAH therefore appears to be the result of increased natriuresis, due to the inappropriate elevation of ANP rather than SIADH. In this situation, water restriction should not be recommended, since the circulatory volume is decreased.

Adult↗

Cloning of cDNA encoding for a novel isozyme of fructose 6-phosphate, 2-kinase/fructose 2,6-bisphosphatase from human placenta.

Two independent cDNA clones encoding fructose 6-phosphate, 2-kinase/fructose 2,6-bisphosphatase were isolated from a human placental cDNA library. The deduced amino acid sequences showed that one of the clones, 2K-1, was almost identical to the rat testis isozyme and the other, 2K-3, was different from any known isozymes expressed in mammalian tissues. The results of Southern blot analysis suggested that clones 2K-1 and 2K-3 were encoded as single copy genes and located in different parts of the genome. Since open reading frames of the cDNA clones were not complete, we obtained the 5'-end of the clone 2K-3 cDNA using the 5'-rapid amplification of cDNA end method. The entire cDNA (HP; 1,756 bp) had a coding capacity of 519 amino acids (M(r) = 59,410), and putative phosphorylation sites for protein kinases A and C on the C terminus. Northern blot analysis using a fragment of the HP as a probe showed that a major band of 5.4 kb, significantly different in size from known isozyme mRNAs such as liver (2.1 kb), muscle (1.9 kb), heart (4.0 kb), and testis (2.0 kb), was present in poly(A)+RNA preparations of human first trimester and term placentae. These results strongly suggested that this 5.4 kb mRNA codes a novel isozyme of fructose 6-phosphate,2-kinase/fructose 2,6-bisphosphatase.

Amino Acid Sequence↗

Renal primitive neuroectodermal tumor: an immunohistochemical and cytogenetic analysis.

The cytogenetic and morphologic characteristics of a case with a primitive neuroectodermal tumor (PNET) arising from the left kidney in a 22 year old man are presented. The patient was detected as having a left renal mass with a tumor embolus in the inferior vena cava and multiple pulmonary metastases. A radical nephrectomy with tumor embolectomy of the inferior vena cava, along with a resection of the pulmonary nodules were performed. Histologic examination revealed a dense proliferation of small round cells with many Homer-Wright type rosettes and perivascular pseudorosettes. Immunohistochemically, the tumor cells stained strongly positive for HBA71(p30/32MIC2), a surface glycoprotein specific to PNET and Ewing's sarcoma. In addition, the tumor cells expressed several neural markers (neuron specific enolase, neurofilament, synaptophysin, and Leu-7) and vimentin, while the epithelial, muscular, and lymphocytic markers were negative in the tumor cells. Cytogenetic analysis of cultured tumor cells showed a reciprocal translocation t(11;22)(q24;q12) that is considered to be specific to PNET and Ewing's sarcoma. In conclusion, this case suggested that a karyotyping analysis is a useful diagnostic tool for renal PNET, and it may therefore be utilized to help distinguish between difficult cases of small round cell tumors and Wilms' tumor of the kidney.

Adult↗

[Pitfalls of three-dimensional computed tomographic angiography as an examination for cerebral aneurysm surgery].

Three-dimensional computed tomography (3D-CT) has recently become available and is being increasingly applied in the field of neuroradiology. One of the procedures, 3D-CT angiography (3D-CTA), has been reported to be more advantageous aneurysms. Some investigators insist that conventional angiography is no longer needed to make the diagnosis. We recently experienced cases in which we were misled or found it difficult to judge the relationship between the aneurysm and surrounding structures by 3D-CTA. Our findings can be summed up as follows: 1) two aneurysms in contact with each other could not be opacified separately, 2) the perforators were hardly opacified at all making it impossible to judge the relationship between the aneurysms and these vessels, an assessment which is very important for delicate operations, 3) the origin of A2 was not clearly opacified as being separate from that another near by aneurysm, 4)part of the severely tortuous middle cerebral artery was interpreted as an aneurysm shadow, 5) even M2 is sometimes not well opacified. In conclusion, 3D-CTA itself is not always a satisfactory method of evaluating the relationship between a cerebral aneurysm and its surrounding vessels. Misleading findings should be kept in mind during direct observation at surgery.

Aged↗

[Serial changes of SPECT and MRI findings in a patient with herpes simplex encephalitis].

We report a case of herpes simplex encephalitis in which the patient was repeatedly examined by magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT). The patient was a 36 year-old woman who had been transferred to our institution 6 days after the onset of symptoms with mild consciousness disturbance, nuchal rigidity, and high fever. Cerebrospinal fluid examination revealed an elevated mononuclear cell count with normal sugar concentration. Intravenous aciclovir was started 7 days after the onset of symptoms. The initial plain computed tomography (CT) scans did not reveal any abnormal findings, but contrast enhanced CT the next day showed a slight enhancement effect around the affected middle cerebral artery. Serial MRI showed the initial high intensity lesion starting on the medial cortex of the temporal lobe, then spreading to throughout the entire temporal lobe. During this period SPECT showed a marked, broad hot spot in the temporal lobe. The medial temporal lobe was high density on the CT 15 days after the onset. As the encephalitic lesion spread more laterally, the hot spot on SPECT moved laterally and then decreased in activity. Eleven weeks after the onset, the MRI showed intracerebral vacuolization of the lesion and it appeared as a wide cold spot on SPECT. The cause of the hot spot seen in the acute period was thought to be vasoparalysis of the affected area rather than breakdown of the blood-brain barrier, or impaired washout of the isotope, because the SPECT images after acetazolamide administration showed the cold spot even in the subacute phase.

Adult↗

[Clinical evaluation of sulbactam/cefoperazone for lower respiratory tract infections. Correlation between the efficacy of sulbactam/cefoperazone and beta-lactamase].

The efficacy and safety of sulbactam/cefoperazone (SBT/CPZ) were evaluated in 42 patients with respiratory tract infections, including pneumonia (29 patients) and lower respiratory tract infections (5 patients). Overall clinical efficacy rates (excellent + good) were 79% in pneumonia and 80% in respiratory tract infections in 34 patients evaluated for clinical efficacy. It was excellent that the clinical efficacy rate was 92% in mild and moderate pneumonia. Pathogens isolated from sputa were 31 strains, including 8 strains of Pseudomonas aeruginosa, 7 of Streptococcus pneumoniae, 3 of Staphylococcus aureus and 3 of Haemophilus influenzae. Since the isolates were eradicated in 18 strains, replaced in 3, unchanged in 2 and unknown in 8, the overall eradication rate was 91%. The eradication rates were 89% in beta-lactamase producing strains and 100% in beta-lactamase positive sputum, and excellent or good in 19 (83%) of 23 patients with beta-lactamase negative sputum. The eradication rate was 88% in 5 patients with beta-lactamase positive sputum. One patient experienced a moderate rash. Abnormal laboratory test values were observed in 10 patients (26.3%), but these abnormalities were mild and transient. These results suggested that SBT/CPZ was effective and safe for the treatment of respiratory tract infections caused by beta-lactamase producing as well as beta-lactamase non-producing bacteria.

Aged↗

A 13-Mer peptide of a brain injury-derived protein supports neuronal survival and rescues neurons from injury caused by glutamate.

Neuronal survival is mediated by several kinds of proteins. Among these, neurotrophic factors play important roles in the nervous system by supporting neuronal activity and survival. It has been suggested recently that certain factors promote neuronal survival in the case of brain injury. To examine this possibility, we purified a novel neurotrophic factor from Gelfoam that was implanted at the site of injury caused in neonatal rats. During amino acid sequence analysis, we found that a fragmental peptide of this neurotrophic protein consisting of 13 amino acids showed neurotrophic activity. This 13-mer peptide promoted survival of septal cholinergic and mesencephalic dopaminergic neurons in culture and rescued hippocampal neurons from injury caused by glutamate in culture. This peptide rescued neurons from cell death caused by glutamate, even when added 4.5 h after glutamate exposure.

Amino Acid Sequence↗

Expression, purification, and neurotrophic activity of amyloid precursor protein-secreted forms produced by yeast.

The secreted form of amyloid precursor protein (APPs) including most of the extracellular domain of APP is released from the cell surface, suggesting physiological significance of APPs in vivo. We used the methylotrophic yeast Pichia pastoris as a host system for the production of recombinant APPs (rAPPs). Two rAPPss derived from isoforms of APP (APP695 and APP770) were secreted into the culture medium from the yeast, which carried cDNA encoding the N-terminal portion of APP under the control of a P. pastoris alcohol oxidase promoter. Like APPss produced by the transfected COS-1 cells, the purified rAPPss from yeast were shown to be biologically active in terms of neurite outgrowth of embryonic rat neocortical explants. These rAPPss could be valuable tools for investigating the biological functions of APPss.

Amino Acid Sequence↗

Oligomannose-coated liposomes as an adjuvant for the induction of cell-mediated immunity.

The effect of the coating of ovalbumin-reconstituted liposomes with various oligosaccharides on their immunogenicity was investigated in mice. The coating of liposomes with oligomannose or yeast mannan drastically enhanced their ability to induce an ovalbumin-specific delayed-type footpad swelling response with a peak at 24 to 48 h post-challenge. Among various oligosaccharides tested, only those with mannose residue at the nonreducing termini manifested the activity when applied to liposomes. Since such oligosaccharides are ubiquitously found in the body, these results suggested the usefulness of oligomannose-coated liposomes as a safe adjuvant for the induction of cell-mediated immunity.

Adjuvants, Immunologic↗

Expression and distribution of low density lipoprotein receptor-related protein mRNA in the rat central nervous system.

The low density lipoprotein receptor-related protein (LRP) is a multifunctional cell surface receptor that binds to the protease inhibitor alpha 2-macroglobulin (alpha 2 M). LRP has also been identified as the apolipoprotein E (apoE) receptor that mediates lipid metabolism. Recently it has been reported that apoE4, one of three common isoforms of apoE, is a main risk factor of Alzheimer's disease (AD). Moreover, all three of these proteins are reported to accumulate in the senile plaques in the brains of Alzheimer's patients. To understand the roles of LRP in the normal development of the central nervous system (CNS) and in the pathogenesis of AD, we studied the developmental expression and localization of LRP mRNA in the CNS. We used Northern blot analysis to investigate the developmental profile of LRP mRNA in the rat brain. LRP mRNA was first detected as early as in 18-day-old embryonic rat brain and was continuously expressed thereafter. A particularly high level of expression of the mRNA was observed in the perinatal stage. We also determined the cellular distribution of LRP mRNA in the CNS of 20-day-old embryonic and 6-week-old adult rat brains by in situ hybridization using a digoxigenin-labeled antisense riboprobe to LRP mRNA. In the embryonic rat brain, LRP mRNA was highly expressed in most of the cells, mainly neurons and glial cells. In the adult rat, LRP mRNA was expressed mostly in neurons in both the brain and the spinal cord. These results suggest that LRP plays crucial roles in development of the brain.

Alzheimer Disease↗

On the conformation of Phe78 of a chromoprotein antibiotic, neocarzinostatin.

A structure of neocarzinostatin, an antitumor chromoprotein antibiotic, has been built using X-ray crystallographic data and NMR data, particularly NOE data observed between the apoprotein and the chromophore. Chemical shift changes of protons of the chromophore upon binding to the apoprotein indicated that the aromatic plane of Phe52 has the conformation almost perpendicular to the C-2-C-3 triple bond of the core of the chromophore while Phe78 takes multiple conformations in solution although one of the stable conformations has been assigned for Phe78 in a crystal structure.

Antibiotics, Antineoplastic↗

Cloning and sequence of the gene encoding a cefotaxime-hydrolyzing class A beta-lactamase isolated from Escherichia coli.

Escherichia coli TUH12191, which is resistant to piperacillin, cefazolin, cefotiam, ceftizoxime, cefuzonam, and aztreonam but is susceptible to cefoxitin, latamoxef, flomoxef, and imipenem, was isolated from the urine of a patient treated with beta-lactam antibiotics. The beta-lactamase (Toho-1) purified from the bacteria had a pI of 7.8, had a molecular weight of about 29,000, and hydrolyzed beta-lactam antibiotics such as penicillin G, ampicillin, oxacillin, carbenicillin, piperacillin, cephalothin, cefoxitin, cefotaxime, ceftazidime, and aztreonam. Toho-1 was markedly inhibited by beta-lactamase inhibitors such as clavulanic acid and tazobactam. Resistance to beta-lactams, streptomycin, spectinomycin, sulfamethoxazole, and trimethoprim was transferred by conjugational transfer from E. coli TUH12191 to E. coli ML4903, and the transferred plasmid was about 58 kbp, belonging to incompatibility group M. The cefotaxime resistance gene for Toho-1 was subcloned from the 58-kbp plasmid by transformation of E. coli MV1184. The sequence of the gene for Toho-1 was determined, and the open reading frame of the gene consisted of 873 or 876 bases (initial sequence, ATGATG). The nucleotide sequence of the gene (DDBJ accession number D37830) was found to be about 73% homologous to the sequence of the gene encoding a class A beta-lactamase produced by Klebsiella oxytoca E23004. According to the amino acid sequence deduced from the DNA sequence, the precursor consisted of 290 or 291 amino acid residues, which contained amino acid motifs common to class A beta-lactamases (70SXXK, 130SDN, and 234KTG). Toho-1 was about 83% homologous to the beta-lactamase mediated by the chromosome of K. oxytoca D488 and the beta-lactamase mediated by the plasmid of E. coli MEN-1. Therefore, the newly isolated beta-lactamase Toho-1 produced by E. coli TUH12191 is similar to beta-lactamases produced by K. oxytoca D488, K. oxytoca E23004, and E. coli MEN-1 rather than to mutants of TEM or SHV enzymes. Toho-1 has shown the highest degree of similarity to K. oxytoca class A beta-lactamase. Detailed comparison of Toho-1 with other beta-lactamases implied that replacement of Asn-276 by Arg with the concomitant substitution of Thr for Arg-244 is an important mutation in the extension of the substrate specificity.

Amino Acid Sequence↗

Inhibition of polar body formation in mouse denuded oocytes cultured in vitro by protein synthesis inhibitors.

Denuded oocytes obtained from the ovaries of ddY mice underwent spontaneous germinal vesicle breakdown (GVBD) and polar body formation (PBF) by cultivation for 3 and 16 h, successively. To study the significance of protein synthesis in oocytes regarding their maturation, denuded oocytes were cultured in the presence of reversible (cycloheximide and puromycin) and irreversible (ricin) protein synthesis inhibitors. When denuded oocytes were cultivated in the continual presence of any inhibitor, only PBF but not GVBD was found to be inhibited. These inhibitions were dose dependent, ranging from 10(-9) to 10(-6) M, and were relative to the protein synthesis inhibitions by them. The PBF inhibition was relieved by withdrawing cycloheximide for first 2, 3 and 4 h in the course of the culture. Further, the PBF inhibition occurred in the presence of ricin for only the first 2 or 3 h in the course of the culture. These results suggested that proteins synthesized during 2 to 4 h in the course of culture may play important role in PBF.

Animals↗