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Biomedical subjects

M Tsuji

Publications and source records attributed to M Tsuji.

At least 91 records · Page 5Linked to original sources

[Metachronous bilateral primary malignant lymphoma of the testis: a case report].

A 72-year-old man was referred to our department with the chief complaint of painless swelling of the left scrotum in May 1997. Left high orchiectomy was performed under the diagnosis of primary testicular tumor. Histological findings revealed non-Hodgkin's lymphoma (NHL) of diffuse, mixed type, B cells. No evidence of tumors in any other site was detected by further examinations. About 3 years and a month earlier, he had undergone right high orchiectomy and postoperative radiotherapy (inverted Y irradiation) and chemotherapy (CHOP 5 cycles) for a right testicular tumor whose histological findings were NHL of diffuse, large cell type, B cells. Metachronous bilateral primary malignant lymphoma of the testis is very rare and we discussed each tumor origin by using IgH gene (IgJHDNA) rearrangement as a tumor specific marker of B cell lineage malignant lymphoma. We discussed the clonality of IgJHDNA rearrangement using polymerase chain reaction (PCR) in each paraffin fragment diagnosed pathologically as NHL of B cell origin.

Aged↗

The possible role of c-fos expression in rheumatoid cartilage destruction.

OBJECTIVE: To determine the effect of c-fos on human chondrocytes and to examine the role of c-fos in cartilage destruction in rheumatoid arthritis (RA). METHODS: We examined changes in collagen synthesis by transfecting human c-fos into cultured human chondrocytes and evaluated expression of c-fos mRNA and localization of Type II collagen, matrix metalloproteinases-1 (MMP-1), and tissue inhibitor of metalloproteinases-1 (TIMP-1) in articular cartilage samples from patients with RA or osteoarthritis (OA) by in situ hybridization and immunohistochemistry. RESULTS: Introduction of c-fos in the chondrocytes decreased endogenous transcription of Type II collagen and TIMP-1, and increased that of MMP-1. The effect of the activating protein-1 protein on the MMP-1 and TIMP-1 promoters in human articular chondrocytes was analyzed by chloramphenicol acetyltransferase activity assay. MMP-1 promoter was clearly activated by Jun related proteins as well as Fos/Jun related protein heterocomplex. On the other hand, c-fos combined with any of the Jun related proteins failed to stimulate the TIMP-1 promoter, although it was activated by Fra-1 or Fra-2/Jun related protein heterocomplexes. Expression of c-fos mRNA was detected in chondrocytes in the mid and deep layers of cartilage in 11/15 patients (73%) with RA, but only in the superficial layer of cartilage from 2/10 patients (20%) with OA. Although TIMP-1 staining exceeded that of MMP-1 in OA cartilage, it appeared to be less intense than MMP-1 staining in RA cartilage. CONCLUSION: These results suggest that activation of c-fos may be involved in cartilage metabolism and hence play a crucial role in the pathogenesis of arthritic destruction in RA.

Adult↗

[First documentation of transfusion-associated babesiosis in Japan].

A 40-year-old man received blood transfusion in December 1998 because of gastric bleeding from a peptic ulcer. One month later, he developed febrile hemolytic anemia. Administration of high doses of glucocorticoid significantly reduced the hemolysis, but did not cure the disease. To investigate the cause of the hemolysis, the patient was transferred to our hospital in May 1999. Giemsa-stained peripheral blood smears showed Babesia parasites in the red blood cells (RBC), and PCR analysis confirmed the presence of Babesia microti DNA. The parasitemia disappeared hematologically after 2 weeks of quinine and clindamycin therapy. However, parasite DNA was still detectable in the RBC. Although treatment with oral atovaquone was given for 2 weeks, parasitemia and febrile hemolysis recurred within a month after the last treatment. Fortunately, complete remission was obtained after a second 12-week course of therapy with quinine and clindamycin. PCR analysis revealed asymptomatic Babesia infection in one of eight samples from the original blood donor. The initial steroid therapy given to the patient without an accurate diagnosis seemed to have delayed augmentation of the specific antibodies (IgG) against Babesia microti, thus prolonging the parasitemia after the initial acute stage of babesiosis.

Adult↗

[Cooperation between public health centers and hospitals in tuberculosis control--how should clinical nurses and public health nurses work together?].

The result of cohort analysis of the patients newly registered from Jan. 1, 1994 until Dec. 31, 1995, showed that 49,824 (84.2%) patients out of a total of 59,150 patients had been cured or completed. On the other hand, there were 1,527 (2.6%) failure cases, 2,521 (4.3%) defaulters, and 5,287 (8.9%) deaths due to TB or other causes. The treatment outcome for smear positive tuberculosis was less favorable. Thus, the Japan's tuberculosis treatment program has not yet achieved the global target of WHO, i.e., the cure rate of 85% of smear positive patients. The Ministry of Health and Welfare declared "TB Emergency" on July 26, 1999. It was a warning to the general public of Japan, as well as to the medical and health professions and central and local governments against their neglect of the tuberculosis problem that has been slow in its improvement since long, and recently has been in upsurge, accompanied by the emergence of formidable problems such as outbreaks of tuberculosis, nosocomial infections and multi-drug-resistant tuberculosis. The public health and the clinical service both have their heavy mission to respond to this declaration hand in hand, fulfilling their respective professional duties to the society. The symposium confirmed that under such situation of the problem, the cooperation between clinical service and public health is very essential and can be very effective in order to improve the results of treatment program for the sake of patients' QOL and for prevention of multi-drug-resistant tuberculosis as well. This was warmly supported by the enthusiasm of the audience with various questions and discussion.

Cohort Studies↗

[Formation mechanisms of stress adaptation: role of functional coupling of glucocorticoids and brain serotonergic nervous system].

It is known that the incompetence of stress adaptation mechanisms is a primary factor affecting disorders such as anxiety and depression. Increased clinical evidence indicates that hyperactivity of the hypothalamo-pituitary-adrenal (HPA) axis and dysfunction of the brain serotonin (5-HT) nervous system are risk factors associated with these disorders. Given the high sensitivity of hippocampal 5-HT responses to glucocorticoids, functional changes in the hippocampal 5-HT nervous system induced by chronic hypercorticism are attracting more attention. Repeated exposure to stress stimuli or chronic administration of corticosterone produces hippocampal 5-HT1A receptor dysfunction as well as an imbalance in mineralocorticoid and glucocorticoid receptors. We recently demonstrated that activation of the 5-HT1A receptors facilitates the adaptive responses to stress stimuli by acting on the HPA axis. These findings suggest that abnormal coupling of glucocorticoid-mineralocorticoid/glucocorticoid receptors-5-HT1A receptors in the hippocampus may be one factor disrupting adaptation to stress situations. Moreover, it is shown that activation of the coupling system affects learning and memory processes associated with stress stimuli. These findings suggest that the functional coupling of glucocorticoid-mineralocorticoid/glucocorticoid receptors and serotonergic neurons in the brain may play a significant role in the recognition of stress stimuli and induction of stress adaptation, and dysfunction of this coupling system may be related to the onset of affective disorders.

Adaptation, Psychological↗

Structure-activity relationship of gramine derivatives in Ca(2+) release from sarcoplasmic reticulum.

5,6-Dibromo-1,2-dimethylgramine evoked Ca(2+) release from skeletal muscle sarcoplasmic reticulum through ryanodine receptors in a concentration-dependent manner with an EC(50) of 22.2 microM. Since the EC(50) of caffeine was 0.885 mM, 5,6-dibromo-1,2-dimethylgramine was 40 times more sensitive than caffeine. Among 14 gramine derivatives having different substituents at N-1, C-2, C-5 or C-6 of the indole skeleton, we found that five derivatives were effective. Study of the structure-activity relationship for Ca(2+) release indicated that 1-methylation and/or both 5- and 6-bromination are important for Ca(2+) release. Thus, gramine derivatives are useful tools for the investigation of Ca(2+) release from sarcoplasmic reticulum.

Alkaloids↗

Antigenic properties of the merozoite surface protein 1 gene of Plasmodium vivax.

Plasmodium vivax is responsible for an approximate 35 million yearly human cases of malaria. Unfortunately, due to the low mortality rate associated with it and the difficulties of continuously in vitro culturing of this parasite, vaccine development against this human malaria has been largely neglected. In here, the antigenic properties of the merozoite surface protein 1 gene of P. vivax (PvMSP-1), were studied. Thus, seven recombinant bacterial plasmids coding different regions of the PvMSP-1 protein were constructed and used to immunize BALB/c mice. The results demonstrated that a plasmid encoding the entire N-terminus comprising 682 amino acids and a plasmid encoding the C-terminus including the two juxtaposed epidermal growth factor (EGF)-like domains fused to the Hepatitis B surface antigen, were antigenic. Moreover, the elicited immune responses were similar to those reported for these same PvMSP-1 regions in natural human infections.

Animals↗

Adrenocortical suppression blocks the enhancement of memory storage produced by exposure to psychological stress in rats.

Several reports have indicated that various stress stimuli modulate learning and memory processes. In the present study, the effects of adrenocortical suppression with the 11beta-hydroxylase inhibitor metyrapone on the psychological stress-induced changes in memory storage in inhibitory avoidance training and in serotonin turnover in various brain regions were investigated in rats. Retention of one-trial inhibitory avoidance and the plasma corticosterone level were significantly enhanced by post-training exposure to psychological stress for 1 h. Pretreatment with metyrapone (12.5 or 25 mg/kg, s.c.) 90 min beforehand dose-dependently blocked the enhancement of memory storage and of the plasma corticosterone level produced by psychological stress. These results suggest that the adrenocortical system may contribute to the memory-enhancing effect of psychological stress. In a neurochemical study, a significant increase in serotonin turnover in the hippocampus and limbic forebrain, including the nucleus accumbens, were observed in rats that were exposed to psychological stress. In contrast to the behavioral experiments, these changes in serotonin turnover produced by exposure to psychological stress were not antagonized by pretreatment with metyrapone; instead, a further increase in serotonin turnover was observed only in the hippocampus. These results suggest that the serotonergic system in the hippocampus might be selectively regulated by adrenal steroids in response to stress, and imply the existence of negative feedback mechanisms via a hippocampal serotonergic system in the memory enhancement associated with corticosterone and psychological stress.

Adrenal Cortex↗

Phenotypic and functional characterization of CD8(+) T cell clones specific for a mouse cytomegalovirus epitope.

A series of CD8(+) T cell clones, specific for the IE1 epitope YPHFMPTNL, of the immediate-early protein 1 of the murine cytomegalovirus (MCMV) were generated in order to determine their protective activity against this infection and correlate their phenotypic markers with antiviral activity. We found that the adoptive transfer of three of these anti-MCMV CD8(+) T cell clones into irradiated naive mice resulted in protection against challenge, while another CD8(+) T cell clone, of the same specificity, failed to confer protection. The clones that conferred protection against lethal challenge reduced greatly viral replication in the lung and other organs of the mice. Using one of the protective anti-MCMV CD8(+) T cell clones we found that in order to be fully protective the cells had to be transferred to recipient mice no later than 1 day after MCMV challenge. The adoptive transfer of these CD8(+) T cell clones also protected CD4(+) T-cell-depleted mice. Phenotypic characterization of the anti-MCMV clones revealed that the nonprotective clone expressed very low levels of CD8 molecules and produced only small amounts of TNF-alpha upon antigenic stimulation. Most importantly, our current study demonstrates that this MHC class I-restricted IE1 epitope of MCMV is efficiently presented to CD8(+) T cell clones in vivo and further strengthens the possibility of the potential use of CD8(+) T cell clones as immunotherapeutic tools against cytomegalovirus-induced disease.

Animals↗

Squamous Cell Carcinoma of the Breast: Three Case Reports.

Three cases of squamous cell carcinoma of the breast, initially diagnosed by fine needle aspiration cytology, are presented. The first case was a 49-year-old woman with a T1 tumor located in the lower outer quadrant of the left breast. Ultrasonography revealed a cystic tumor. Aspiration cytology suggested squamous cell carcinoma (SCC). Mastectomy was performed. Histological examination revealed a pure SCC. The second case was a 40-year-old woman with a T1 tumor located in the upper outer quadrant of the right breast.Ultrasonography showed a cystic tumor and aspiration cytology revealed SCC. A quad-rantectomy was performed. Histological examination revealed predominant SCC with an adeno-carcinoma component. Estrogen receptor (ER) was negative. The patient received postoperative radiation. Thirteen months after the first operation,a salvage mastectomy was performed because of local recurrence. The third case was a 61-year-old woman with a T1 tumor located in the upper outer quadrant of the right breast. Ultrasonography showed a solid tumor. Aspiration cytology revealed both SCC and adenocarcinoma. Wide excision was performed. Histological examination revealed pre-dominant SCC with foci of adenocarcinoma. ER was negative. She received postoperative radiation. The three patients are alive and disease-free 10 to 54 months after operations

Journal Article↗

Intussusception of a mucocele of the appendix secondary to an obstruction by endometriosis: report of a case.

We treated a patient with a complete invagination of the cecum which contained a mucocele of the appendix secondary to an obstruction by endometriosis. Preoperatively, a barium enema showed a crab's claw-like area without filling in the oral side of the transverse colon. An emergency laparotomy was performed and revealed a mucocele of the appendix to have induced appendicecal invagination; however, no colonic invagination was observed. An appendicecal resection was thus done. Pathologically, the resected specimen was a mucosal hyperplasia with mucin-secreting lesions of the appendix. The theories regarding the pathogenesis of appendicecal mucocele are reviewed and discussed.

Adult↗

Transport kinetics of leucine enkephalin across Caco-2 monolayers: quantitative analysis for contribution of enzymatic and transport barrier.

In this study, we determined the activities of four aminopeptidases such as aminopeptidase B (APB), M (APM), N (APN) and dipeptidylpeptidase IV (DPP IV) in Caco-2 cells and compared with those in the rat intestinal mucosae. The activities of APB, APM and APN appeared to be highest in rat small intestinal mucosa, while DPP IV activity was much higher in Caco-2 cells than that in the rat intestinal mucosa. Next the inhibitory effects of various protease inhibitors were examined in Caco-2 homogenate. Three tested inhibitors, bacitracin, amastatin and puromycin, effectively inhibited the activities of APM, APN and DPP IV except for APB. Further, we quantitatively evaluated the permeation and degradation properties of leucine enkephalin (Leu-Enk) in the presence or absence of inhibitors in Caco-2 monolayer system. Leu-Enk had a high degradation clearance (CLd) and a low permeation clearance (CLp) in Caco-2 monolayers. This finding indicates that the very rapid degradation of Leu-Enk on the apical side of Caco-2 monolayers was due to aminopeptidases. However, these protease inhibitors besides sodium glycocholate were able to reduce the CLd values markedly, thereby increasing the permeation amount of Leu-Enk across Caco-2 monolayers. In particular, amastatin significantly decreased the CLd value and increased the CLp value. This enhanced CLp value was further increased by the coadministration with an absorption enhancer, EDTA or laurylmaltoside. These findings are relevant to the oral administration of peptide drugs and to developing an efficient oral delivery system.

Aminopeptidases↗

Region-dependent G-protein activation by mu-, delta 1- and delta 2-opioid receptor agonists in the brain: comparison between the midbrain and forebrain.

The ability of selective mu- ([D-Ala2, NHPhe4, Gly-ol]enkephalin: DAMGO), delta1- ([D-Pen2, Pen5]enkephalin: DPDPE) and delta2- ([D-Ala2]deltorphin II: DELT II) opioid receptor agonists to activate G-proteins in the midbrain and forebrain of mice and rats was examined by monitoring the binding of guanosine-5'-O-(3-[35S]thio)triphosphate ([35S]GTPgammaS). The levels of [35S]GTPgammaS binding stimulated by DAMGO in the mouse and rat midbrain were significantly greater than those by DPDPE or DELT II. However, relatively lower levels of stimulation of [35S]GTPgammaS binding by all of the agonists than would have been predicted from the receptor densities were observed in either the limbic forebrain or striatum of mice and rats. The effects of DAMGO, DPDPE and DELT II in all three regions were completely reversed by selective mu-, delta1- and delta2-antagonists, respectively. The results indicate that the levels of mu-, delta1- and delta2-opioid receptor agonist-induced G-protein activation in the midbrain are in good agreement with the previously determined distribution densities of each receptor type. Furthermore, the discrepancies observed in the forebrain might reflect differential catalytic efficiencies of receptor-G-protein coupling.

Analgesics, Opioid↗

Role of endothelin receptor subtypes in the behavioral effects of the intracerebroventricular administration of endothelin-1 in conscious rats.

The role of endothelin receptor subtypes, i.e., ET(A) and ET(B) receptors, in the behavioral effects of the intracerebroventricular (ICV) administration of endothelin-1 were examined in conscious rats. ICV administration of endothelin-1 (1-9 pmol/rat) dose dependently produced barrel rolling and other convulsive behaviors including bodily twitching, rigidity, back crawling, fore/hindlimb dystonia, fore/hindlimb clonus, tail extension, and facial clonus. Moreover, a marked increase in spontaneous locomotor activity was observed in animals that were treated with a low dose of endothelin-1 (1 pmol/rat, ICV). Endothelin-1 (9 pmol/rat, ICV)-induced barrel rolling and other convulsive behaviors were completely suppressed by the coadministration of BQ-123 (15 nmol, ICV), a specific endothelin ET(A) receptor antagonist, but not of BQ-788 (15 nmol/rat, ICV), a specific endothelin ET(B) receptor antagonist. In contrast, increased locomotor activity produced by treatment with a low dose of endothelin-1 (1 pmol/rat, ICV) was antagonized by coadministration of BQ-788, but not of BQ123. These results indicate that endothelin-1, which has affinity for both endothelin ET(A) and ET(B) receptors, most likely acts on central ET(A) receptors to evoke barrel rolling and other convulsive behaviors. In addition, activation of central ET(B) receptors may be involved in the increase in spontaneous locomotor activity. These results suggest that brain endothelin receptor subtypes may be involved in the regulation of various physiological functions.

Animals↗

Congenital fiber type disproportion: severe form with marked improvement.

A 30-month-old male exhibited marked hypotonia at birth accompanied by respiratory distress necessitating ventilator support. He subsequently demonstrated marked improvement in muscle power. He became independent of the respirator at 21 days of age and was able to sit without support at 11 months and walked alone at 24 months. Histopathologic analysis of the quadriceps femoris muscle confirmed the diagnosis of congenital fiber type of disproportion at 11 months of age. No other studies have described a patient with a severe neonatal form of congenital fiber type of disproportion who demonstrated such clear improvement. Physicians should be aware of this possibility when they interact with such patients and their families.

Child, Preschool↗