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Biomedical subjects

M Tsuji

Publications and source records attributed to M Tsuji.

At least 145 records · Page 8Linked to original sources

Ovarian teratoma with gliomatosis peritonei: report of two cases.

Gliomatosis peritonei, a rare condition related to ovarian teratomas, involves the peritoneal implantation of numerous nodules of predominantly mature glial tissues. We report herein the cases of two patients with immature ovarian teratoma associated with gliomatosis peritonei, in one of whom a rapid progression of teratomatous implants occurred 14 weeks after her initial surgery. Gliomatosis peritonei is considered benign in most cases; however, some reports have documented the rapid recurrence of immature peritoneal implants, as implantation is associated with teratomas of all grades. Thus, in the face of peritoneal implants suspected to be of a teratomatous nature, thorough and extensive sampling is essential to exclude the presence of immature elements which may imply a poor prognosis and require aggressive therapy.

Ascitic Fluid↗

Five familial hypercholesterolemic kindreds in Japan with novel mutations of the LDL receptor gene.

In the course of investigations of familial coronary artery disease in Hokkaido, the northern island of Japan, we identified five families in which multiple members showed elevated plasma levels of low-density lipoprotein (LDL) cholesterol. To determine the genetic etiology of their lipoprotein abnormalities, we screened DNA samples from these families for mutations in all 18 exons and the exon-intron boundaries of the LDL receptor (LDLR) gene. Novel point mutations were identified in each family: (1) a C-to-A transversion at nucleotide 285, causing a nonsense mutation at codon 74, in eight members of family A; (2) a G-to-A transition at nucleotide 1136, causing substitution of Tyr for Cys at codon 358, in six members of family B; (3) a C-to-T transition at nucleotide 1822, causing substitution of Ser for Pro at codon 587, in five members of family C; (4) a one-base insertion of G to a five-G stretch at nucleotides 1774-1778 (codons 571-572), causing a frameshift, in six members of family D; and (5) a one-base deletion of T at nucleotide 1963-1964 (codon 634), causing a frameshift, in three members of family E. Through the molecular genetic approach a total of 28 individuals in these families were diagnosed unequivocally as heterozygous for the respective LDLR mutations. This method also helped us to diagnose familial hypercholesterolemia, or to exclude from carrier status, 11 children with borderline high cholesterol levels.

Adolescent↗

Babesia canis infection in canine-red blood cell-substituted SCID mice.

We have developed a mouse model for Babesia canis infection using severe combined immunodeficiency (SCID) mice whose circulating red blood cells had been substituted with canine red blood cells. Substitution of red blood cells in SCID mice was achieved by repetitive transfusions of canine red blood cells, together with administration of an antimouse red blood cell monoclonal antibody. Following inoculation of canine-red blood cell-SCID mice with B. canis, parasites proliferated in the canine red blood cells that had been transfused into the SCID mice, resulting in much higher parasitaemia than that observed in dogs. In an attempt to demonstrate the utility of this mouse model, three antiprotozoal drugs, diminazene diaceturate, clindamycin and oxytetracycline, were examined for their efficacy to inhibit the growth of B. canis in canine-red blood cell-SCID mice. The mouse model clearly showed that diminazene diaceturate and oxytetracycline were capable of eliminating B. canis from the canine-red blood cell-SCID mice, whereas clindamycin exhibited only a static effect as parasitaemia relapsed upon cessation of drug administration.

Administration, Cutaneous↗

Sequence analysis of the major piroplasm surface protein gene of benign bovine Theileria parasites in east Asia.

Relatively benign Theileria parasites are widespread among cattle in East Asia. Although the parasites are presumed to be of the Theileria sergenti/Theileria buffeli/Theileria orientalis group, their taxonomic status and epidemiology have not been well defined. In the present study, theilerial DNA samples were collected from various East Asian countries, including Japan, Korea, Taiwan, and China. DNA sequences encoding a major piroplasm surface protein were amplified by polymerase chain reaction, followed by cloning into a plasmid vector. More than 20 DNA clones derived from parasite DNA of a single infected animal were examined for their restriction-fragment-length polymorphism, showing that they were classified into four major types. Sequence analysis revealed six types of DNA sequences encoding major piroplasm surface protein with homologies of between 75 and 91%. Of the six sequences, four were identical to those previously reported, while the other two appeared to be new sequences. Among the DNA clones derived from a single infected animal, two to three distinct sequences were often found. Phylogenetic analysis of the six major piroplasm surface protein sequences indicates that five of the six are closely related to each other, and that all are distantly related to the homologous genes of Theileria annulata and Theileria parva. The results suggest that, in addition to those described as T. sergenti/T. buffeli/T. orientalis, there may be some undefined Theileria species distributed in East Asia, and that many cattle are infected with mixed populations of geographically variable Theileria parasites.

Amino Acid Sequence↗

Role of the matrix metalloproteinase and tissue inhibitors of metalloproteinase families in noninvasive and invasive tumors transplanted in mice with severe combined immunodeficiency.

OBJECTIVES: To elucidate the role of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in human urothelial cancers, we studied gene expressions of MMPs, TIMPs, and membrane-type 1 matrix metalloproteinase (MT1-MMP) in noninvasive or invasive tumor lines transplanted in mice with severe combined immunodeficiency (SCID). METHODS: The UCT-1 tumor line, derived from bladder cancer, is a noninvasive transplantable tumor with no evidence of metastasis. The UCT-2 tumor line, derived from a renal pelvic tumor, extensively invades without metastasis. We examined gene expressions of MMPs-1, 2, 3, 7, 8, 9, 10, and 11, TIMPs-1, 2, and 3, and MT1-MMP in UCT-1 and 2 by semiquantitative polymerase chain reaction analysis. RESULTS: Significantly higher gene expression of MMP-2 was detected in the invasive UCT-2 tumor line than in the noninvasive UCT-1 tumor line. Although both tumor lines expressed TIMP-1 and MT1-MMP, stronger gene expression of MT1-MMP was observed in the UCT-2 tumor line than in the UCT-1 tumor line. The other MMPs or TIMPs were not detected in either of the lines. CONCLUSIONS: MMP-2 and MT1-MMP may have an important role in the invasion mechanism of urothelial cancers.

Aged↗

Mannan decelerates the clearance of human red blood cells in SCID mouse.

Mannans and its related compounds decelerated human (Hu) red blood cell (RBC)-clearance in severe combined immunodeficiency (SCID) mice by inhibiting erythro-phagocytosis of macrophages. Chimeric SCID mice for Hu-RBC which are generated by repeated transfusions with mature Hu-RBCs are described recently as a model for Plasmodium falciparum infection, though the Hu-RBC clearance in the mice at present is very rapid and the parasitemia in the mice is only erratic. Here, we aimed to study the method to decelerate Hu-RBC clearance in SCID mice, to establish a suitable mouse model for malaria parasites. Yeast and Candida mannans as well as lactoferrin, a glycoprotein containing both oligomannoside- and N-acetyllactosamine-type glycans, decelerated Hu-RBC clearance, but instead other saccharides such as carboxymethyl chitin, N-acetylglucosamine, and D-glucose did not. Yeast mannan and lactoferrin interfered significantly with in vitro Hu-RBC-phagocytosis which was also inhibited by mannopentaose and mannotoriose. D-mannose exhibited a moderate inhibitory activity. N-acetyl-D-glucosamine, however, showed only a slight inhibitory activity, but D-glucose had no inhibitory activity on Hu-RBC phagocytosis. These results may postulate that Hu-RBC clearance in SCID mouse might be mediated by receptor-ligand binding by a macrophage lectin like receptor with mannose specificity.

Acetylglucosamine↗

Efficient induction of protective anti-malaria immunity by recombinant adenovirus.

The immunogenicity of a previously constructed replication-defective recombinant adenovirus expressing the CS protein of Plasmodium yoelii was compared with that of irradiated sporozoites. We found that immunization of BALB/c mice with a single dose of this recombinant adenovirus induced a much greater CS-specific T-cell response compared with immunization with irradiated sporozoites. More importantly, we found that this recombinant adenovirus induces similar or higher levels of protective immunity than those induced by irradiated sporozoites, eliciting an appreciable resistance to malaria infection.

Adenoviridae↗

Spheno-orbital meningioma with unusual radiological features.

We report a patient with a spheno-orbital meningioma having unusual clinical and radiological features. Eight days before consultation, this 66-year-old female developed right exophthalmos associated with periorbital pain. Neuroradiological features included, (1) multilocular intratumoral cyst on enhanced CT, (2) preferential extradural growth with prominent bony destruction and intratumoral hemorrhage on MRI. and (3) early venous draining on CAG. Histopathology including immunohistochemistry and electron microscopy revealed typical transitional meningioma. The only uncommon pathological feature was that the attachment consisted of the outer (periosteal) layer of the dura, and the microscopic structure of the inner (meningeal) layer was normal.

Aged↗

Phenotypic differences between T-->C and T-->G mutations at nt 8993 of mitochondrial DNA in Leigh syndrome.

This study reports on a patient with Leigh syndrome with a T-to-C mutation at nucleotide 8993 of mitochondrial deoxyribonucleic acid (T8993C). The authors reviewed 10 Leigh syndrome patients, including ours, with T8993C. Compared with 18 reported patients with Leigh syndrome caused by a T-to-G mutation at nucleotide 8993 (T8993G), Leigh syndrome with T8993C was characterized by a significantly higher frequency of ataxia (P < 0.01). None of the reviewed T8993C-associated Leigh syndrome patients had retinitis pigmentosa, which is one of the characteristic findings in Leigh syndrome with T8993G. The milder symptoms of T8993C-Leigh syndrome can be explained by the milder complex V dysfunction; however, the higher frequency of ataxia in T8993C-Leigh syndrome requires more study.

Child, Preschool↗

Helicobacter pylori infection induces cyclooxygenase-2 expression in human gastric mucosa.

Recent studies indicate that expression of mitogen-inducible cyclooxygenase-2 (COX-2) occurs in gastrointestinal tumors. We investigated the effects of Helicobacter pylori (H. pylori) infection, a class I carcinogen for the human stomach, on gastric COX-2 expression using immunohistochemistry. Human subjects without macroscopic lesions, as determined by endoscopic screening, were biopsied for H. pylori infection. The biopsy samples were immunohistochemically examined for COX-2 expression. COX-2 was expressed in gastric epithelia and subepithelial inflammatory cells in all H. pylori-infected subjects. There was no expression of COX-2 in the gastric mucosa of H. pylori-negative subjects. COX-2 expression has been reported in gastrointestinal carcinomas, gastrointestinal cancer cell-lines, and in the gut after carcinogenic treatment. The present study demonstrates that H. pylori infection leads to gastric mucosal expression of COX-2, indicating that the enzyme is involved in H. pylori-related gastric pathology in humans.

Adult↗

Later onset of apoptosis in the bulbourethral glands after castration compared to that in the seminal vesicles.

Androgens affect many different target organs within the male reproductive tract to stimulate their development and secretory cytodifferentiation, and to maintain structure and function in adulthood. Castration causes regression of these organs via apoptosis. However, not all organs of the reproductive tract are equally sensitive to androgen withdrawal. The effects of castration on the mouse seminal vesicles (SVs) and bulbourethral glands (BUGs) were compared in terms of protein and DNA contents, epithelial apoptosis, and proliferative response of epithelial cells to androgen. Castration induced similar, marked decreases in protein contents in the SV and BUG by 2 days after castration which reached a minimum at 16 days post castration. Both organs underwent a decrease in DNA content, but the kinetics of this decline differed. In the SV, DNA content was significantly decreased by 4 days whereas in the BUG this did not occur until 16 days post castration. By day 16 both organs had regressed to roughly the same degree. The apoptotic index in the epithelium reflected this difference in timing as well. Apoptotic index of the SV epithelium was highest on day 3 after castration and declined thereafter. On the other hand, the apoptotic index in the BUG didn't begin to increase until 7 days after castration and became maximal on day 12. Daily injections of testosterone propionate (TP) from day 8, 16, or 30 after castration all increased epithelial labelling index in the SVs to a similar degree. However, the TP-induced increase in the epithelial labelling index in the BUG beginning on day 8 after castration was considerably less than that in BUGs receiving TP treatment from day 16 or 30 after castration. Thus, the proliferative response of the epithelium depended upon prior apoptosis in the gland, with the timing being delayed in the BUG as compared with the SV. The present results indicate that castration induces epithelial apoptosis and reduction in glandular DNA content considerably later in the BUG than in the SV though reduction in protein content in the BUG fell simultaneously with that in the SV.

Animals↗

Immunohistochemical analysis of Ki-67 antigen and Bcl-2 protein expression in prostate cancer: effect of neoadjuvant hormonal therapy.

OBJECTIVE: To determine differences in the immunohistochemical (IHC) expression of Bcl-2 protein and Ki-67 antigen in patients with prostatic cancer who underwent radical prostatectomy with or without neoadjuvant hormonal therapy. MATERIALS AND METHODS: Ki-67 antigen and Bcl-2 protein were detected by IHC using MIB-1 and Bcl-2 antibodies in prostatectomy specimens from 28 patients who received hormonal therapy before surgery (group 1) and 51 patients who did not (group 2). RESULTS: In group 2, the mean MIB-1 index increased with increasing grade of tumour, from 11.6% in low-grade to 24.7% in high-grade tumours (P = 0.002). Bcl-2 expression did not correlate with either tumour grade or stage. In group 1, there were no correlations between Bcl-2 expression or MIB-1 index and tumour grade or stage. More tumours in group 1 were Bcl-2-positive (16 of 28, 57%) than were tumours in group 2 (11 of 51, 22%; P = 0.003). The mean (SD) MIB-1 index of tumours in group 2 [15.6 (14.4)%], was significantly greater than that of tumours in group 2 [6.8 (7.5)%; P = 0.004]. CONCLUSIONS: These results indicate that Bcl-2 positivity is increased by androgen ablation therapy and conversely, that the proliferative activity of cancer cells is significantly reduced. The expression of Bcl-2 protein may play a role in the ability of prostate cancer cells to survive in an androgen-deprived environment.

Aged↗

Immediate effects of extracorporeal shock waves on the male genital system of rabbit. Preliminary report.

Hemospermia was reported to occur following extracorporeal shock wave lithotripsy of lower ureteric stones. Because no studies showed clearly the possible effect of extracorporeal shock waves (ESW) on the male genital system, we were prompted to study this effect. Eighteen male white New Zealand rabbits were divided into three groups (six in each) and subjected to different doses of ESW (2000, 3000 and 4000) using a Dornier MFL 5000. Shocks were focused on the lower parts of the bladder. Four animals were used as controls. Two hours later, the animals were dissected. Gross examination of the genital systems showed bleeding in the testicles and prostates of only some animals, whereas microscopic examination revealed bloody spots in the genital structures of all animals. The amount of bleeding was ESW dose-independent. In conclusion, ESW showed evident immediate effects on the male genital system. Application of shock waves in treating lower ureteric or vesical stones in doses between 2000 and 4000 may cause bleeding in the structures of this system, which can lead to hemospermia. More studies will be needed to show the long-term sequelae of these changes on the male genital system.

Animals↗

Oral administration of (-)catechin protects against ischemia-reperfusion-induced neuronal death in the gerbil.

The effect of ad libitum oral-administration of (-)catechin solution on ischemia-reperfusion-induced cell death of hippocampal CA1 in the gerbil was histologically examined. When (-)catechin solution instead of drinking water was orally administered ad libitum for 2 weeks, dose-dependent protection against neuronal death following by transient ischemia and reperfusion was observed. To evaluate the involvement of reduction of reactive-oxygen-species (ROIs) by the antioxidant activity of (-)catechin in this protection, the superoxide scavenging activity of the brain in catechin-treated gerbils was measured by ESR and spin-trapping using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). The superoxide scavenging activities of the brains obtained from catechin-treated gerbils were significantly higher than those of catechin-untreated animals. From these results, it was suggested that orally administered (-)catechin was absorbed, passed through the blood-brain barrier and that delayed neuronal death of hippocampal CA1 after ischemia-reperfusion was prevented due to its antioxidant activities.

Administration, Oral↗

In vitro and in vivo antibacterial activities of S-4661, a new carbapenem.

The in vitro and in vivo antibacterial activities of S-4661, a new 1beta-methylcarbapenem, were compared with those of imipenem, meropenem, biapenem, cefpirome, and ceftazidime. The activity of S-4661 against methicillin-susceptible staphylococci and streptococci was comparable to that of imipenem, with an MIC at which 90% of the strains tested were inhibited (MIC90) equal to 0.5 microg/ml or less. S-4661 was highly active against members of the family Enterobacteriaceae, Haemophilus influenzae, and Moraxella catarrhalis, with MIC90s ranging from 0.032 to 0.5 microg/ml. Against imipenem-resistant Pseudomonas aeruginosa, S-4661 was the most active among test agents (MIC90, 8 microg/ml). Furthermore, S-4661 displayed a high degree of activity against many ceftazidime-, ciprofloxacin-, and gentamicin-resistant isolates of P. aeruginosa. The in vivo efficacy of S-4661 against experimentally induced infections in mice caused by gram-positive and gram-negative bacteria, including penicillin-resistant Streptococcus pneumoniae and drug-resistant P. aeruginosa, reflected its potent in vitro activity and high levels in plasma in mice. We conclude that S-4661 is a promising new carbapenem for the treatment of infections caused by gram-positive and -negative bacteria, including penicillin-resistant S. pneumoniae and drug-resistant P. aeruginosa.

Animals↗

Recombinant Sindbis viruses expressing a cytotoxic T-lymphocyte epitope of a malaria parasite or of influenza virus elicit protection against the corresponding pathogen in mice.

Subcutaneous administration in mice of recombinant Sindbis viruses expressing a class I major histocompatibility complex-restricted 9-mer epitope of the Plasmodium yoelii circumsporozoite protein or the nucleoprotein of influenza virus induces a large epitope-specific CD8(+) T-cell response. This immunization also elicits a high degree of protection against infection with malaria or influenza A virus.

Animals↗

Differentiation of the inhibitory effects of calcium antagonists on abnormal behaviors induced by methamphetamine or phencyclidine.

The abnormal behaviors induced by methamphetamine (MAP: 1 mg/kg) or phencyclidine (PCP: 10 mg/kg) were measured using behavioral analysis following the microinjection of one of three calcium (Ca) antagonists (nifedipine: Nif, nicardipine: Nic and flunarizine: Flu) into the rat caudate putamen or amygdala. The intraperitoneal administration of MAP or PCP induced abnormal behaviors in a time-dependent manner; the maximum locomotor activity was measured 30-45 min after the administration of MAP or PCP. This hyperactivity was sustained for more than 2 h. Following microinjection of these Ca antagonists into the caudate putamen, each showed a different pattern of inhibition on MAP- or PCP-induced abnormal behaviors. Nic and Flu were effective at reducing these abnormal behaviors, in contrast, Nif was ineffective. In particular, the inhibitory effect of Nic was stronger than that of Flu. Microinjection of these Ca antagonists into the amygdala did not show any reductive effect on the hyperactivity induced by MAP or PCP. These results demonstrate that these Ca antagonists have different pharmacological properties and that both L- and T-type Ca2+ channels modulate the dopamine release in the rat caudate putamen. These results further lead us to suggest the presence of a subtype of L-type Ca2+ channels in the caudate putamen.

Amygdala↗

Near infrared spectroscopy detects cerebral ischemia during hypotension in piglets.

We have previously reported concordant changes in cerebral intravascular oxygenation measured by near infrared spectroscopy (NIRS) and mean arterial blood pressure (MAP) in premature infants. We hypothesized that the cerebral oxygenation changes are caused by MAP-induced alterations in cerebral blood flow (CBF) and studied these parameters in neonatal piglets (n = 6). Changes in cerebral intravascular oxygenation were measured by NIRS from the hemoglobin difference (HbD) signal (oxyhemoglobin-deoxyhemoglobin). CBF was measured by the radioactive microsphere technique. The cerebral circulation was also monitored by Doppler determinations of CBF velocity (time average mean velocity) in the anterior cerebral artery. Hypotension to <50% of baseline MAP was achieved by a ligature around the ascending aorta. Arterial oxygenation was maintained constant by mechanical ventilation. As observed in our studies of premature infants, cerebral HbD and MAP showed concordant changes. Hypotension was accompanied by significant decreases both in CBF (42.8 +/- 12.5% of baseline p < 0.01) and HbD (-65.0 +/- 22.0 micromol/L x dpf, p < 0.01). HbD was significantly correlated with MAP (p < 0.05) and time average mean velocity (p = 0.01). Importantly, decreases in cerebral total hemoglobin (HbT), a measure of cerebral blood volume, did not correlate significantly with decreases in MAP. We conclude that 1) decreases in cerebral intravascular oxygenation, as assessed by NIRS, observed with decreases in MAP reflect a decline in CBF, and hence oxygen delivery, 2) the HbD signal is more sensitive to changes in CBF than the HbT signal, and 3) NIRS recordings may have clinical utility in detecting cerebral ischemia.

Animals↗