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Biomedical subjects

Y Fujimori

Publications and source records attributed to Y Fujimori.

At least 19 recordsLinked to original sources

Molecular cloning and characterization of mouse ficolin-A.

A novel ficolin-related gene was isolated from the mouse liver lambda ZAPII cDNA library. The protein encoded by this gene consists of both collagen- and fibrinogen-like domains, which are common features of the ficolin family, and was named mouse ficolin-A. The amino acid sequence of mouse ficolin-A is 60.2, 59.8, 59.8, and 59.6% identical to those of porcine ficolin-alpha, -beta, human ficolin-1, and EBP-37/P35, respectively. Northern blot analysis showed that mRNA of mouse ficolin-A is highly expressed in liver and spleen. Immunoblot analysis using an anti-mouse ficolin-A antiserum showed that mouse ficolin-A is a plasma protein with binding activity to elastin and GlcNAc.

Acetylglucosamine

Multiple carcinoids of the duodenum accompanied by type I familial multiple endocrine neoplasia.

A case of multiple carcinoid tumors of the duodenum accompanied by familial multiple endocrine neoplasia is reported. A 46-year-old man with duodenal polyps discovered during a mass screening was followed up for 5 years. In August 1994, a histological examination revealed carcinoid tumors, and he was thus referred to our hospital for surgery. He underwent a parathyroidectomy and cholecystectomy for primary hyperparathyroidism and cholecystolithiasis, respectively. The patient's sister had also undergone a parathyroidectomy and distal pancreatectomy for primary hyperparathyroidism and insulinoma of the pancreas. In addition, his two children were also followed up for hypercalcemia. A serum examination of the patient revealed high levels of somatostatin and pancreatic polypeptide, but normal levels of gastrin and serotonin. In November 1994, a pancreaticoduodenectomy with a D2 lymph node dissection was performed. The macroscopic findings of the resected specimen showed multiple polypoid lesions with delles on the top, measuring 3 to 15 mm in size throughout the duodenum. A microscopic examination revealed the tumor to have infiltrated into the submucosa extensively, and an immunohistochemical analysis also demonstrated the tumor cells to be positive for somatostatin, but not for pancreatic polypeptide. After surgery, the serum level of somatostatin returned to normal but the pancreatic polypeptide remained high. The post-operative course was uneventful, and the patient remains in good health.

Carcinoid Tumor

Recombinant human erythropoietin for late-onset anemia after allogeneic bone marrow transplantation.

Recombinant human erythropoietin (rHu EPO) has been reported to accelerate early erythroid reconstitution after bone marrow transplantation (BMT). We conducted a pilot study on rHu EPO for late-onset anemia in 9 patients after allogeneic BMT. The patients achieved initial erythropoietic recovery (hemoglobin (Hb) range 9.1-13.4, mean 10.8 g/dl), but then developed transplant-related anemia (Hb range 6.3-9.7, mean 8.2 g/dl) more than 50 days after BMT. This type of anemia was related to graft-versus-host disease (GVHD), cytomegalovirus infection, and/or impaired EPO secretion. The patients received 3,000 or 12,000 U of rHu EPO subcutaneously three or seven times weekly. Hb levels increased by more than 2 g/dl in 6 of the 9 patients, but were unchanged in the 3 patients with severe GVHD. These findings suggest that in some cases rHu EPO is effective for the treatment of late-onset anemia after BMT.

Adult

Myelodysplastic syndrome with B cell clonality in a patient five years after renal transplantation.

A female patient received a renal transplantation from an unrelated cadaver donor, and five years later developed myelodysplastic syndrome (MDS) with immunological abnormalities. Chromosomal analysis showed trisomy 8 in bone marrow cells. FISH analysis indicated that trisomy 8 was present in 4% of CD19 + cells, suggesting that the MDS clone involved B lymphocytes. Polymerase chain reaction of the human androgen receptor gene indicated B cell clonality (54%) and granulocyte clonality (63%). There have been no previous reports of secondary MDS following renal transplantation in which the MDS clone involved the B cell lineage. The abnormal MDS B cell clone may have caused the immunological abnormalities.

B-Lymphocytes

The levels of soluble P-selectin, von Willebrand factor and thrombomodulin in patients with neurological complications after allogeneic bone marrow transplantation.

We encountered two patients with uncommon neurological manifestations after allogeneic bone marrow transplantation (BMT), which occurred with rapid elevation of the leukocyte count at engraftment. Both patients then developed severe acute graft-versus-host disease (GVHD). To investigate the pathogenesis, we measured the levels of soluble P-selectin, von Willebrand factor (vWF) and thrombomodulin (TM), which reflect endothelial damage. The P-selectin, vWF and TM levels in the patients with (n=2) and without (n=5) neurotoxicity were, respectively, 168.5+/-52.5 ng/ml vs 27.7+/-3.9 ng/ml, 6.7+/-0.15 FU/ml vs 3.42+/-0.41 FU/ml and 459+/-37% vs 189.4+/-32.4% (mean+/-s.d.). All three parameters were much higher in the patients with neurological complications. These results suggest that neurotoxicity after BMT may be related to endothelial damage.

Adult

Significance of trilineage myelodysplasia in de novo acute myeloid leukaemia during remission rather than at diagnosis.

Patients with trilineage myelodysplasia (TMDS) in de novo acute myeloid leukaemia (AML) at diagnosis and remission were clinically evaluated between 1983 and 1996. AML with TMDS (AML/TMDS) was observed in 20 (12%) of 162 patients with de novo AML at diagnosis. Complete remission (CR) was achieved with combination chemotherapy in 12 (67%) of 18 AML/TMDS cases. This CR rate was relatively worse than the rate of 78% (106/136 cases) of AML without TMDS, but this difference was not significant. Disease-free survival curves also showed no difference between AML/TMDS and AML without TMDS. During remission, eight (67%) of 12 AML/TMDS cases had myelodysplastic remission marrow (AML/MRM). AML/MRM was also seen in seven (7%) of 106 AML cases without TMDS. The actuarial disease-free survival was significantly lower in AML/MRM than in AML without MRM (P = 0.0003). All of the AML/MRM cases exhibited early leukaemic relapse; median remission duration was only 9 months. Clonal changes occurred in two cases of AML/TMDS and five cases of AML/MRM at the time of relapse. These findings suggest that TMDS during remission predicts a poorer prognosis and early leukaemic relapse when compared with the absence of TMDS.

Acute Disease

Hepatic and splenic sarcoidosis evaluated by multiple imaging modalities.

We present a case of hepatosplenic sarcoidosis. A 51-year-old Japanese male, who was diagnosed to have sarcoidosis 4 years previously, was presented to our hospital because of dry cough and anorexia with weight loss. He had tender hepatosplenomegaly. A dynamic abdominal computed tomography (CT) revealed multiple small low-density areas in both liver and spleen, as well as in magnetic resonance imaging (MRI). The laparoscopic photographs showed many small whitish nodules surfacing on the liver and several tumorous nodules on the spleen. Multiple imaging modalities including dynamic CT and MRI are valuable for detecting focal hepatic and splenic lesions of sarcoidosis.

Biopsy

Measuring the diameter of coronary arteries on MR angiograms using spatial profile curves.

OBJECTIVE: The spatial profile curve of the nuclear MR intensity across the short axis of a coronary artery in an MR angiogram results in a gradual up-and-down slope lacking sharp definition, which indicates that display parameters may influence edge recognition. Therefore, our study was designed to determine the appropriate window setting and to devise a method of accurately measuring the diameter or width of the artery independent of window parameters. CONCLUSION: The diameter of a coronary artery measured on MR coronary arteriography significantly varied with experimentally selected display parameters. When compared with the diameter on contrast-enhanced coronary arteriograms, the window center on MR angiograms at the midpoint between the peak intensity of the intravascular lumen and the background intensity and the window width of a quarter or a half of the intensity difference between the two were proven to be appropriate. The angiographic diameter corresponded to the diameter obtained at 65% +/- 9% of the peak intensity on the spatial profile curve across the short-axis MR coronary angiogram. Accordingly, 65% of the peak intensity indicates the diameter of the coronary artery. Thus, the intensity profile curve independent of the window setting provided a new method for measurement of the diameter of the coronary artery.

Adult

4-Hydroxycatecholestrogen metabolism responses to exercise and training: possible implications for menstrual cycle irregularities and breast cancer.

OBJECTIVE: To investigate the behavior of C4-substituted estrogens, the so-called catecholestrogens, in response to acute exercise and training. The 4-hydroxyestrogens are known to have both a strong estrogenic potency and affinity for catechol-O-methyltransferase (COMT), the enzyme that deactivates catecholamines. DESIGN: A prospective trial covering three menstrual cycles: a control cycle, a moderate training cycle, and a heavy training cycle. PARTICIPANT(S): Six untrained, healthy, eumenorrheic women (mean pretraining maximum oxygen uptake: 40.9 +/- 4.9 mL/kg per minute, body fat: 27.9% +/- 3.6%) volunteered for this study. INTERVENTION(S): An incremental exercise test to exhaustion on a cycle ergometer, in the follicular and luteal phases, before and after a brief but exhaustive training program. MAIN OUTCOME MEASURE(S): Hormone measurements included follicular and luteal phase plasma E2, LH, catecholamines, PRL, total unconjugated and conjugated estrogens, total 4-hydroxyestrogens (4-OHE), and 4-hydroxyestrogen-monomethylethers (4-MeOE). RESULT(S): Pretraining baseline 4-OHE levels were significantly higher in the luteal phase (66 +/- 9 pg/mL; mean +/- SEM) than in the follicular phase (51 +/- 7 pg/mL). Pretraining and post-training baseline 4-MeOE values were below minimal detection limits (< 35 pg/mL). During incremental exercise, catecholamines, PRL, E2, unconjugated and conjugated estrogens, 4-OHE, and 4-MeOE always increased (the increases in 4-OHE during exercise were more pronounced before training, contrary to the 4-MeOE being most increased after training). The baseline 4-MeOE:4-OHE ratio (a measure of catecholestrogen activity) significantly increased with progressive training. CONCLUSION(S): Because 4-OHE have been shown to be able to control the hypothalamic gonadotropin oscillator and to stimulate the luteolytic prostaglandin PGF2 alpha, the acute exercise-induced increases of 4-OHE and their positive correlation with lactate levels may indicate a key process in the pathogenesis of exercise-associated menstrual irregularities. In addition, 4-OHE, when insufficiently O-methylated, are known to be capable of raising mutagenic superoxide free radicals and causing DNA damage that may lead to breast cancer. The results of the present study also may be of significance for the apparent protective effects of sports participation against cancer of the breast.

Adult

Correlation between immunological abnormalities and prognosis in myelodysplastic syndrome patients.

Immunological abnormalities (IA) are frequently observed in patients with myelodysplastic syndromes (MDS). Although there have been a number of analyses of the prognostic factors, there have been few studies, if any, to determine whether IA affects prognosis. We investigated the prognosis of 153 MDS patients with or without IA who were treated at a single Japanese institute for 10 years. Nineteen of 153 patients (12%) developed autoimmune disorders. One hundred of 153 patients (63%) had an abnormality in at least one immunological laboratory test. Hypergammaglobulinemia was found in 50 of 128 (39%) patients tested, hypogammaglobulinemia was observed in 10 of 128 (8%), positivities of antinuclear antibody, RA factor. DNA antibody, and direct antiglobulin test were observed in 30%, 14%, 7% and 12%, respectively, and a CD4/CD8 ratio < 1 was observed in 20%. There was no significance in the distribution of age, MDS subtype, or sex between patients with and without IA. The survival of MDS patients without IA was significantly better than that of patients with IA, and the survival of patients with a CD4/CD8 ratio > 1 was also significantly superior to the survival of those with an inverted CD4/CD8 ratio. Patients with IA tended to die of infection or leukemic progression in comparison with those without IA, suggesting that IA may be associated with susceptibility to opportunistic infection and disease progression.

Adult

Growth hormone-releasing hormone (GRH)-producing pancreatic tumor with no evidence of multiple endocrine neoplasia type 1.

The characteristic features of a 48-year-old male presenting with isolated acromegaly caused by a GRH-producing pancreatic endocrine tumor bearing no relation to MEN1 was reported. The clinical features, laboratory findings, and sellar enlargement were improved after removal of the pancreatic tumor. The resected pancreatic tumor showed positive GRH immunoreactivity and contained abundant GRH mRNA. This tumor is extremely rare and to date only 10 cases have been reported. In the management of acromegaly, the measurement of GRH is recommended and the search for an ectopic source will prevent unnecessary and potentially ineffective pituitary surgery.

Acromegaly

Successful treatment of severe cytomegalovirus retinitis with foscarnet and intraocular injection of ganciclovir in a myelosuppressed unrelated bone marrow transplant patient.

A female patient with ALL received a bone marrow transplant (BMT) from an unrelated donor with a one locus HLA mismatch. The donor was heterozygous at the HLA-A locus, while the patient was homozygous at this locus. The patient had cytomegalovirus (CMV) antigenemia on day 42 following an intensive preparative regimen that included anti-thymocyte globulin and BU+CY+TBI to prevent graft rejection. Ganciclovir was given initially for the treatment of CMV antigenemia, although the patient soon developed severe myelosuppression. The patient's hematopoietic recovery was poor, and CMV and human herpesvirus-6 (HHV-6) were detectable in the peripheral blood. Severe CMV retinitis was treated with foscarnet and the intraocular injection of ganciclovir. The CMV retinitis improved and the marrow gradually recovered. CMV and HHV-6 were no longer detectable in the peripheral blood. Foscarnet and intraocular injection of ganciclovir appeared to be an effective treatment for CMV retinitis in this myelosuppressed BMT patient.

Adult

Spontaneous remission of desquamative interstitial pneumonia.

We report a case of spontaneous remission of desquamative interstitial pneumonia (DIP) in a 50-year-old male. The histological diagnosis of DIP was based on open lung biopsy. A chest X-ray revealed reticulo-nodular shadows in the bilateral lung fields, and the patient had mild dyspnea on exertion. Without treatment, these shadows decreased gradually and disappeared after several months. The patient recovered completely within one year, and recurrence of the disease has not been observed for 4 years. Recently, DIP has rarely been described, and the spontaneous remission of DIP has not been reported since Carrington et al in 1978 (1).

Biopsy

[Juvenile onset of idiopathic interstitial pneumonia].

A 22-year-old first man came to our hospital because of dyspnea on exertion in February 1993, and was admitted in September 1994 because of progression of dyspnea. A chest roentgenogram showed diffuse ground-glass-opacities in the middle and lower lung fields, and an elevated diaphragm. Pulmonary-function testing revealed a low %VC and a low diffusing capacity. Examination of a specimen obtained by thoracoscopic lung biopsy revealed usual interstitial pneumonia. Immunohistochemical examinations showed the expression of intercellular adhesion molecule-1 on vascular endothelial cells and on alveolar epithelial cells. Dust inhalation and collagen vascular disease were ruled out and the diagnosis was idiopathic interstitial pneumonia. This condition develops only rarely in patients under 60 years old.

Adult

[A case of papillary adenocarcinoma of the stomach with liver metastases and carcinomatous peritonitis treated effectively by methotrexate/5-fluorouracil sequential chemotherapy].

A 54-year-old male was admitted to receive treatment by anticancer drug for advanced gastric cancer with liver metastases and carcinomatous peritonitis. Upper gastrointestinal series showed a Borrmann type 4 gastric cancer occupying the body and antrum, and a pathological diagnosis of papillary adenocarcinoma was made by endoscopic biopsy. Two cycles of neoadjuvant chemotherapy consisting of 5-FU and low-dose CDDP (FP therapy) were given. No effect was observed, so that the next chemotherapy schedule of sequential MTX/5-FU therapy was performed. We adopted the intermediate (MTX: 100 mg/m2 and 5-FU 600 mg/m2 weekly) dose regimen. When six courses of this regimen were completed, the primary lesion of the stomach was decreased to 60% and the metastatic liver tumor to 72%, basel on criteria for the evaluation of clinical effects of solid cancer chemotherapy. However, pylorous stenosis remained, and we performed gastrojejunostomy and biopsy of the regional lymph node to determine the response to the chemotherapy. A pathological examination of lymph node revealed metastatic papillary adenocarcinoma with xanthogranulomatous change, and was judged as an effect showing grade 2. He was discharged and had the outpatient hospital treatment. He died of exacerbation of carcinomatous peritonitis 10 months after his initial admission. The response duration for sequential MTX/5-FU therapy was 4 months. This therapy was usually effective in patients with poorly differentiated adenocarcinoma of the stomach. Our result indicates that this therapy can be effective for not only poorly differentiated adenocarcinoma but also papillary adenocarcinoma of the stomach in an advanced stage.

Adenocarcinoma, Papillary

Induction of thrombolysis and prevention of thrombus formation by local drug delivery with a double-occlusion balloon catheter.

The efficacy of the local delivery of an antithrombotic drug in preventing thrombosis and enabling thrombolysis was investigated in 29 dogs. An antithrombotic drug (heparin, 25 U/kg), or an antithrombin (argatroban, 0.05 mg/kg) was infused into injured canine iliac arteries, using a double-occlusion balloon catheter, and the preventive effect of the drug was evaluated. Local delivery of low-dose tissue-type plasminogen activator (t-PA; Tisokinase, 50,000 U; Kowa, Nagoya and Asahi Chemical Industries, Fuji, Japan) into thrombosed canine iliac arteries, using the same catheter, or intravenous infusion of low-dose or high-dose t-PA (30,000 U/kg) was also performed. Angiographically, stenotic thrombosis was 2% by local delivery of argatroban and 7% by local delivery of heparin (P < 0.01 vs each control; 47% and 51% respectively). Thrombotic stenosis, as observed by angiography, decreased from 91% to 9% after local delivery of t-PA, and from 94% to 52% in controls. Local delivery of t-PA effectively reduced the thrombus size (P < 0.01 vs control). After systemic intravenous delivery of low-dose t-PA, no reduction of residual thrombotic stenosis, was observed. Reduction of residual thrombotic stenosis after intravenous delivery of high-dose t-PA, was similar to that achieved by local delivery of the drug. Angioscopy demonstrated a similar trend. High-dose drug delivery reduced systemic coagulability. Local delivery of an antithrombotic drug, using a double-occlusion balloon catheter, effectively prevented thrombus formation, and local delivery of t-PA induced thrombolysis without exerting a significant influence on coagulability.

Angioscopy