Biomedical subjects

E Yamazaki

Publications and source records attributed to E Yamazaki.

At least 37 records · Page 2Linked to original sources

PubMed1997

Eradication of minimal residual disease during graft-versus-host reaction induced by abrupt discontinuation of immunosuppression following bone marrow transplantation in a patient with Ph1-ALL.

We observed a patient in whom graft-versus-host disease (GVHD) appeared to induce a positive effect. This 32-year-old male with Philadelphia chromosome-positive acute lymphoblastic leukemia received a bone marrow transplant (BMT) from an HLA-identical sibling donor. We analyzed the bone marrow with the reverse transcriptase-polymerase chain reaction to screen for the minor bcr/abl transcript, which indicates the presence of minimal residual disease (MRD). MRD was present in the pre- and post-transplant phases. There was no evidence of acute GVHD by post-transplant day 45. We abruptly discontinued the immunosuppressive therapy in an attempt to eliminate MRD by inducing an antileukemic reaction during GVHD. GVHD associated with diarrhea and liver dysfunction developed on day 64. On day 105, MRD disappeared and GVHD was treated with prednisolone and cyclosporin. The disappearance of MRD may have been due to the graft-versus-leukemia (GVL) effect mediated by the alloimmune response of donor T lymphocytes. These findings suggest that induction of the GVL effect may be useful for eliminating MRD after BMT in leukemia patients at high risk of recurrence of the disease.

Adult↗

PubMed1997

Variant of intron 22 inversions in the factor VIII gene in severe hemophilia A.

Recurrent DNA inversions, which disrupt the factor VIII (FVIII) gene, generally occur between a region of intron 22 (int22h) and one of two homologous copies of this region, located 300 to 400 kb telomeric to the FVIII gene. This report describes a patient with severe hemophilia A and a high level inhibitor with atypical hybridization patterns. A Bcl I Southern blot assay was altered to 17.5, 16, and 14 kb. His mother and two out of four aunts tested had normal and abnormal restriction patterns which led to a total of five different fragments, suggesting that they were carriers. The Xba I plus Kpn I restriction fragment-length polymorphism in intron 22 by Southern blotting using the same probe (probe a) yielded the 6.2 kb polymorphic band, with a clearly separated 6.6 kb band from the non-factor VIII region; an alternative int22h hybridization probe (probe x) detected no additional fragment. These results suggest that probe a as well as probe x could recognize an intron-22-sized fragment. This report shows a variation in the number of int22h copies although we could not find the inversion junction.

Adult↗

PubMed1997

Autoantibody selectively inhibits binding of von Willebrand factor to glycoprotein ib. Recognition site is located in the A1 loop of von Willebrand factor.

A 20-year-old man with severe von Willebrand disease recently presented a progressive bleeding tendency, characterized recurrent subcutaneous hemorrhages and cerebral hemorrhage. Mixing and infusion studies suggested the presence of an inhibitor directed against vWF:RCo activity of von Willebrand factor (vWF) without significant inhibition of the FVIII:C. The inhibitor was identified as an antibody of IgG class. The inhibitor inhibited the interaction of vWF in the presence of ristocetin and that of asialo-vWF with GPIb while it partially blocked botrocetin-mediated interaction of vWF to GPIb. The inhibitor reacted with native vWF, the 39/34 kDa fragment (amino acids [aa] 480/ 481-718) and the recombinant vWF fragment (MalE-rvWF508-704), but not with Fragment III-T2 (heavy chains, aa 273-511; light chains, aa 674-728). A synthetic peptide (aa 514-542) did not inhibit vWF-inhibitor complex formation. We conclude that this is the first auto-antibody of class IgG from human origin that recognizes the sequence in the A1 loop of vWF, resulting in a virtual absence of functional vWF and a concomitant severe bleeding tendency although recognition site is different from the residues 514-542 which is crucial for vWF-GPIb interaction.

Adult↗

PubMed1997

[Graft-versus-leukemia effect induced by abrupt discontinuation of cyclosporine A following allogeneic bone marrow transplantation].

Cyclosporine A (CyA) was abruptly discontinued in an attempt to induce graft-versus-leukemia (GVL) effect following allogeneic bone marrow transplantation (BMT). It appeared that GVL effect was co-expressed with graft-versus-host disease (GVHD) in 2 of 4 patients and especially minimal residual disease was eliminated during GVHD in a patient with Philadelphia-positive acute lymphocytic leukemia. Subpopulation of cytotoxic T and natural killer cells increased significantly in patients with discontinuation of CyA. This finding suggests that GVL effect was increased following discontinuation of CyA. These results may provide a therapeutic strategy after BMT in patients with high-risk group for relapse of leukemia.

Acute Disease↗

PubMed1996

Induction of sister chromatid exchange in the presence of gadolinium-DTPA and its reduction by dimethyl sulfoxide.

RATIONALE AND OBJECTIVES: The authors investigate the frequency of sister chromatid exchange (SCE) after the addition of gadolinium (Gd)-DTPA to venous blood samples. METHODS: Venous blood was obtained from nonsmokers. Samples were incubated with Gd-DTPA alone or in combination with mitomycin C, cytarabine, and dimethyl sulfoxide (DMSO), and then evaluated for SCEs. RESULTS: The frequency of SCE increased with the concentration of Gd-DTPA and as each chemotherapeutic agent was added. Sister chromatid exchange frequencies were lower when the blood was treated with a combination of Gd-DTPA and DMSO compared with Gd-DTPA alone. DISCUSSION: The increase in frequency of SCE seen after the addition of Gd-DTPA was decreased by the addition of DMSO, indicating the production of hydroxyl radicals. The effect likely is dissociation-related.

Cells, Cultured↗

PubMed1996

Suppression of human pancreatic cancer growth in BALB/c nude mice by manumycin, a farnesyl:protein transferase inhibitor.

Activating mutations of Ki-ras have been detected in most human pancreatic adenocarcinomas. Since Ras protein requires farnesylation to function, we investigated the effects of manumycin, a potent farnesyl:protein transferase inhibitor, on the growth in nude mice of a human pancreatic cancer cell line, MIA PaCa-2, with a point mutation in the Ki-ras gene. Tumor-bearing mice received intraperitoneal injection of 1 or 5mg/kg manumycin daily for 5 days, or 2 mg/kg manumycin daily for 2 weeks. Growth of inoculated tumors was significantly inhibited by the treatment. The treatment significantly (P<0.05) lowered the numbers of bromodeoxyuridine-incorporating tumor cells. Manumycin did not have apparent hepatotoxicity in vivo. Farnesyl:protein transferase inhibitors could offer a new approach for cancer chemotherapy.

Alkyl and Aryl Transferases↗

PubMed1996

[Chronic myelocytic leukemia associated with cytomegalovirus induced sialoadenitis after unrelated allogeneic bone marrow transplantation].

A 26-year-old male with chronic myelocytic leukemia was admitted for unrelated allogeneic bone marrow transplantation (BMT). After BMT, he developed swelling of biateral submandibular glands accompanied with pneumonitis possibly due to cytomegalovirus (CMV). Biopsy from the left submandibular gland showed giant cells with nuclear inclusion bodies that were positive for anti-CMV-IE monoclonal antibody, there fore cytomegalic sialoadenitis was diagnosed. The administration of ganciclovir resulted in resolution of the pnumonitis and submandibular gland swelling. Although cytomegalic sialoadenitis is not a life-threating complication in BMT patients, it should be noted that biopsy is very useful for the diagnosis of systemic cytomegalovirus infection.

Adult↗

PubMed1996

[Hypoplastic mixed lineage leukemia successfully treated with low-dose cytosine arabinoside].

A 54-year-old male was admitted because of dyspnea on exercise. His peripheral blood revealed pancytopenia with severely hypoplastic bone marrow. Bone marrow aspiration showed a marked hypocellular marrow with 62.4% of blast cells. Cytochemical studies showed that peroxidase activity, alpha-nephtyl buthylate esterase activity and PAS reaction were negative, and that only ASD-chroloacetate esterase activity was positive. Surface marker analysis of blast cells showed positive result for CD5, 7, 33 and 34 antigens. The T-cell receptor beta gene was rearranged, but the immunoglobulin H chain gene showed a germ line configuration. Terminal Deoxynucleotydyl Transferase (TdT) was positive, but cellular surface and cytoplasmic immunoglobulin were not recognized. A diagnosis of hypoplastic mixed lineage leukemia was made and treated with low dose cytosine arabinoside, he resulted in complete remission. The relation between hypoplastic leukemia, AML-M0 and mixed lineage leukemia was also discussed.

Antimetabolites, Antineoplastic↗

PubMed1996

[Acute appendicitis caused by mucorales in a patient with severe aplastic anemia: report of an autopsy case].

A male patient with severe aplastic anemia was admitted for bone marrow transplantation. While waiting for a donor, high doses of methylprednisolone, anabolic steroid and granulocyte colony stimulating factor were given without response. Deferoxamine was administered for prophylaxis of hemochromatosis because of high level of ferritin. Acute right lower abdominal pain and pyrexia developed. A diagnosis of acute appendicitis was made and appendectomy was performed. The histopathological examination of the resected appendix revealed necrotizing hemorrhagic appendicitis with numerous hyphae of Mucorales. Though anti-fungal agent (amphotericin B) administration was continued, he subsequently developed ileo-cecal abscess and eventually died due to myoglobinuric nephropathy caused by extensive necrosis of the iliopsoas muscle. Autopsy revealed dissemination of hyphae of Mucorales in lungs, kidneys, large vessels and muscle of the bilateral lower limbs. Systemic vascular invasion and embolization of fungal hyphae were also observed. However, culture of exudate sampled from ileocecum yielded no Mucorales. It was emphasized that antemortem diagnosis and effective anti-fungal treatments are essential for the management of intestinal mucormycosis. The relation ship between mucormyocosis and deferoxamine was also discussed.

Acute Disease↗

PubMed1996

Acquired type 2A von Willebrand disease in chronic myelocytic leukemia.

Acquired von Willebrand disease (vWD) has been described in a few patients with chronic myelocytic leukemia (CML). We present here acquired type 2 vWD associated with CML and provide characterization of an inhibitor to von Willebrand factor (vWF) from this patient. His bleeding time was prolonged. Ristocetin-induced platelet agglutination was abolished whereas botrocetin-mediated aggregation was normal. Multimeric analysis of vWF from patient's plasma showed that larger sizes of multimers were reduced. His past and family histories were negative for bleeding tendency. These results suggested that acquired type 2 vWD was present during his clinical course. The inhibitor was purified by Staphylococcal protein A, suggesting an IgG antibody. Both binding of 125I-vWF to GPIb and platelet agglutination by ristocetin were inhibited by the patient IgG with the concentrations of competing substances necessary to inhibit specific binding by 50% (IC50s) of 260 micrograms/ml and 420 micrograms/ml, respectively. However, the IgG had no effect on these studies mediated by botrocetin. The IgG only reacted with intact vWF and a 39/34 kDa fragment of vWF. These results indicate that the recognition of GPIb binding site(s) on vWF by the IgG is a central pathogenesis of acquired type 2 vWD in this case.

Bleeding Time↗

PubMed1994

Cold agglutinin disease following allogeneic bone marrow transplantation.

We describe a case of cold agglutinin disease (CAD) following allogeneic bone marrow transplantation. This 36-year-old male developed CAD 3 weeks after allogeneic bone marrow transplantation for chronic myelogenous leukemia. Cyclosporin A and methotrexate had been administered to prevent graft-versus-host disease. Other agents administered included cytomegalovirus hyperimmune globulin and recombinant human G-CSF. Pericarditis preceded the development of CAD. The characterization of cold agglutinin (CA) was monoclonal IgM-kappa with anti-Pr antigen specificity, probably derived from the engrafted donor lymphocytes. The administration of prednisolone led to transient improvement. The CA titer decreased without further treatment 12 weeks after transplant.

Adult↗

PubMed1993

[Current status of Pasteurella multocida infection in Japan].

Recently, the case reports of Pasteurella multocida infection has been increasing in Japan. In 1989, the Japanese Government, Veterinary Sanitation Division, Ministry of Health and Welfare officially communicated this infection as a zoonosis to related institutions. The current status of Pasteurella multocida infection is not well known in Japan. Because of this, a nation wide questionnaire survey on Pasteurella multocida was conducted to clarify the status. A questionnaire was sent to 380 laboratories of the hospitals, and 258 (67.9%) replied. An infectious disease caused by Pasteurella multocida was found in Japan in 369 cases in 115 (44.6%) of 258 hospitals, or an average of 3.2 cases per hospital. The 369 cases were broken down into 123 males (from 1 month old to 87 years old), 118 females (from 7 months old to 88 years old), and 128 patients whose sex was unknown. The incidence of the infections tends to increase year by year. This incidence is higher than our expectation. It is considered that the contact with pets will in increase the infection with this agents. The organism was isolated in as many as nineteen different body specimens, including the appendix and urine, which in Japan has not been reported as organs harboring this organism. Some of the nineteen cases were severely infected. This organism was isolated most often from the sputum (48.5%). Pus was the next most common site (27.1%). This order was reversed in the U.K. and the U.S.. Possible explanations for the reversal are given below.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1993

Effect of Gd-DTPA and/or magnetic field and radiofrequency exposure on sister chromatid exchange in human peripheral lymphocytes.

The effects of a magnetic field, radiofrequency, and gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) on the sister chromatid exchange (SCE) in human peripheral lymphocytes were investigated. Whole blood was taken from a nonsmoker and samples were exposed to magnetic force (1.5 T) alone, and to a magnetic force combined with radiofrequency waves (63.86 MHz, specific absorption rate, SAR, 0.4 W/kg). Gd-DTPA was then added to other blood samples in varying amounts and concentrations. After exposure to the conditions described above, these blood samples were cultured for 69 hours. Slides were made for an SCE evaluation. As the concentration of Gd-DTPA added to the blood increased, the SCE frequency also increased. However, the addition of Gd-DTPA at the clinical concentrations normally used did not affect the SCE frequency.

Gadolinium DTPA↗

PubMed1992

[A 13-week subcutaneous toxicity study of prednisolone farnesylate (PNF) in rats].

The toxicity of Prednisolone farnesylate (PNF), a synthetic glucocorticoid, was investigated in the Sprague-Dawley rat. PNF was injected subcutaneously at doses of 0.03, 0.3, 3 and 30 mg/kg/day for 13 weeks. In addition, 18.7 mg/kg/day prednisolone (PN), which is approximate to 30 mg/kg/day PNF in prednisolone molarity, was also administered to the rat for comparison. The results are summarized as follows: 1. All animals from the PN 18.7 mg/kg/day group, and four(4) out of ten(10) males and three(3) out of ten(10) females from the PNF 30 mg/kg/day group died having shown weakened condition such as unkempt fur and emaciation. Histopathologically, systemic suppurative inflammation, as shown by pyeronephritis and abscess formation in many organs and tissues, was observed and it was considered that the administration of steroid induced weakened condition and systemic suppuration which resulted in death. In addition, atrophy was noted in the adrenal glands, lymphatic organs and skin, and histopathological lesions were also observed in the lungs, liver, pancreatic islets, bone, bone marrow and mammary glands. 2. Surviving animals in the PNF 30 mg/kg/day group showed almost the same changes as those observed in the dead animals that died. Hematological examination revealed an anemic change and a decrease in lymphocytes with an increase in segmented neutrophils and eosinophils. In the urinalysis and blood chemistry, the changes suggesting damages to the liver and kidneys were mainly observed. 3. In the PNF 3 and 0.3 mg/kg/day groups, several changes such as atrophy of the adrenal glands, lymphatic organs and skin were noted in a dose dependent manner. 4. In the PNF 0.03 mg/kg/day group, ther were no toxic signs. 5. Based on these results, it was concluded that the overt toxic dose of PNF was 0.3 mg/kg/day and the non-toxic dose was 0.03 mg/kg/day in the present study.

Animals↗

PubMed1992

[A 13-week dermal toxicity study of prednisolone farnesylate (PNF) gel in rats with a recovery period of 5 weeks].

The toxicity of Prednisolone farnesylate (PNF) gel, a synthetic glucocorticoid, was investigated in the Sprague-Dawley rat. PNF gel was administered dermally to the rats at doses of 0.25, 1, 4 and 16 mg/kg/day for 13 weeks, then the drug was withdrawn for 5 weeks to evaluate the reversibility. In addition, 10 mg/kg/day prednisolone gel (PN gel), which is approximate to 16 mg/kg/day PNF gel in prednisolone molarity, was also administered to the rats for comparison. The results are summarized as follows: 1. In the PNF gel 16 mg/kg/day group, temporary erythema at the application site, retarded body weight gains, a decrease in the white blood cell count and lymphocyte ratio with an increase in the segmented neutrophil ratio, an elevation of serum AIP activity were observed. The pathological examinations revealed atrophy of the adrenal glands, lymphatic organs and skin. In addition, histopathological lesions were also found in the liver, pancreatic islets, bone, bone marrow and mammary glands. 2. In the PNF gel 4 mg/kg/day group, retarded body weight gains were observed, and histopathological lesions were noted in the adrenal glands, lymphatic organs, skin at the application site, liver and bone marrows. 3. In the groups that received less than 1 mg/kg/day of PNF gel, there were no toxic signs induced by the drug. 4. In the PN gel 10 mg/kg/day group, drug-related changes were almost similar to those of the PNF gel group, but the severity of the lesions was stronger than in the PNF gel group. 5. After the 5-week recovery period, the above changes almost completely disappeared and so it was demonstrated that the changes were reversible. 6. Based on these results, it was concluded that the overt toxic dose of PNF gel was 4 mg/kg/day and the non-toxic dose was 1 mg/kg/day in the present study.

Administration, Cutaneous↗

PubMed1992

[A 52-week oral chronic toxicity study of 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino] benzoate dimethanesulfonate (FUT-187) in rats with a recovery period of 5 weeks.

The chronic toxicity of FUT-187, a synthetic protease inhibitor, was investigated in Sprague-Dawley rats. FUT-187 was given orally to the rats at doses of 0.4, 2, 10, 50 and 250 mg/kg/day for 52 weeks. The drug was then withdrawn for 5 weeks. The results are summarized as follows: There were no deaths or toxic signs caused by the drug throughout the experimental period. There were no drug-related changes in food consumption, ophthalmological examination, hematology or blood chemistry. Slight suppression of growth was observed in males in the 250 mg/kg group. This change was reversed on withdrawal of the drug. Drug crystals were observed in the urinary sediments of both sexes in the 250 mg/kg group, but this change disappeared on withdrawal of the drug. Gross pathological examination revealed the following changes: enlargement and nodule formation in the pancreas in both sexes given more than 10 mg/kg of the drug; dark red spots in the glandular stomach in males in the 250 mg/kg group; thickening of the small intestinal walls in both sexes given more than 50 mg/kg. Of these organs, no changes were observed in the stomach and small intestine at the end of the recovery period. Increased pancreas weight was observed in both sexes given more than 50 mg/kg of the drug. Examination at the end of the recovery period suggested reversibility, showing a lesser degree of change. Histopathological examination revealed the following changes in the pancreatic acinar cells: acidophilic foci and nodules in both sexes given more than 10 mg/kg of the drug; adenoma in one male in the 250 mg/kg group; increased zymogen granules in both sexes given more than 50 mg/kg of drug; fine vacuolization in females in the 250 mg/kg group. At the end of the recovery period, increased zymogen granules and fine vacuolization of the acinar cells were not found. Furthermore, erosion or healed erosion in the glandular stomach, duodenum and jejunum was observed in a few males or females in the 250 mg/kg group, but those changes disappeared after the recovery period. In the liver, altered cell foci was observed more frequently in males in the 250 mg/kg group than the other groups, but this change also disappeared after the recovery period. In addition, brown pigmentation in the proximal renal tubules of the kidney was observed in both sexes in the 250 mg/kg group, but lesions observed in the examination after the recovery period were less noticeable than in the examination at the end of the administration period.

Administration, Oral↗

PubMed1992

[A 13-week subacute oral toxicity study of 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl) amino] benzoate dimethanesulfonate (FUT-187) in rats].

The toxicity of FUT-187, a synthetic protease inhibitor, was investigated in Sprague-Dawley rats. FUT-187 was given orally to the rats at doses of 2, 10, 50, 250 and 1250 mg/kg/day for 13 weeks, then the drug was withdrawn for 5 weeks for recovery. The results are summarized as follows: In the 1250 mg/kg/day group, 9 out of 20 males died with decreased body weight and exhaustion. Histopathological examination revealed renal papillary necrosis, ulcer in the urinary bladder, hemostatic lesions in the lungs and liver, ulcer or erosion in the stomach, duodenum and jejunum. The surviving animals in this group showed swelling of the limbs due to synovitis, transient salivation immediately after administration, suppression of growth with decreased food consumption. Urinalysis revealed a low pH, increased ketones and bilirubin excretion, dark yellowish change in color, the appearance of "leaflet-shaped" crystals and increased red blood cells and epithelial cells in the urinary sediment, increased water intake, decreased specific gravity and decreased sodium, potassium and chloride in the urine. Hematologically, there was an increase in the white blood cell count. A biochemical analysis of the blood revealed decreased amylase activity, glucose and total protein levels and increased GOT activity and inorganic phosphorus levels. Pathological changes were observed in the pancreas, kidney, digestive tract, urinary bladder and liver. The pancreas showed macroscopical enlargement and increased organ weight. Histopathologically, there were several alterations in the acinar cells, such as vacuolization due to increased fat droplets, nuclear irregularity, prominent nucleoli, irregular arrangement and vesiculation of rough endoplasmic reticulum (rER), dilatation of developed Golgi apparatus and increased free ribosomes. In the kidney, increased weight and pigmentation in the proximal tubular epithelium were noted. Electron microscopically, these pigments were recognized as secondary lysosomes containing filamentous material and electron dense granules within a lucent matrix. In the digestive tract, ulcer or erosion in the stomach and duodenum, and villous proliferation in the small intestine were observed. Furthermore, hyperplasia and vacuolization were noted in the mucosal epithelium of the urinary bladder. In addition, loss of perilobular fat droplets in the liver and increased adrenal weight without histological change were observed. After a 5-week recovery period, these changes disappeared almost completely. In the 250 mg/kg/day group, slight suppression of growth the appearance of "leaflet-shaped" crystals in the urinary , sediment, increased water intake and decreased sodium in the urine were observed. The pancreas showed enlargement, increased weight, acinar cell hypertrophy with increased zymogen granules, fine vacuolization, slight derangement and vesicular of rER, and dilatation of Golgi apparatus.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗

PubMed1992

Comparison of CT findings in non-Hodgkin lymphoma and squamous cell carcinoma of the maxillary sinus.

The findings at CT in 11 patients with primary non-Hodgkin lymphoma (NHL) of the maxillary sinus were compared with the CT findings in 21 patients with squamous cell carcinoma (SCC) of the maxillary sinus. In NHL, the segmental bone destruction was in alignment with the bony wall with a massive tumor infiltration into the neighboring structures. In contrast, all patients with SCC were characterized by a soft tissue mass with aggressive bone destruction. About half of the patients with NHL had cervical lymphadenopathy. Post-treatment recalcification of previous bone destruction was seen in 4 out of 5 NHL patients on follow-up CT. In the patients with SCC, only a few had metastatic lymphadenopathy, and no recalcification occurred after treatment. CT is therefore of importance in differentiating NHL from SCC of the maxillary sinus.

Aged↗