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Biomedical subjects

K Toyama

Publications and source records attributed to K Toyama.

At least 91 records · Page 5Linked to original sources
PubMed1998

[Diffuse panbronchiolitis with myeloperoxidase-specific antineutrophil cytoplasmic antibody-related vasculitis].

A 46-year-old woman was referred to our department in July 1996 with complaints of fever and myalgia in her calves. She had a 20-year history of purulent sputum; diffuse panbronchiolitis had been diagnosed in 1983. Physical examination revealed low-pithed rhonchi over the lung fieldis and hypesthesia of the right leg. She had a white blood cell count of 16,100/mm3, including 4% eosinophils, and a platelet count of 80.0 x 10(4)/mm3. The serum IgE level was 2,200 U/ml, and the cold hemagglutinin titer was high. Pulmonary-function tests showed mixed ventilatory dysfunction, and arterial blood gas analysis revealed a PaO2 of 55.8 Torr on room air. Pseudomonas aeruginosa was cultured from her sputum. A chest X-ray film and CT scan showed diffuse nodular shadows and bronchiectatic changes with mild hyperinflation. An infiltrative lesion in right S6 area could also be seen. Administration of broad-spectrum antibiotics did not alleviate her symptoms. The level of myeloperoxidase-specific antineutrophil cytoplasmic antibody (MPO-ANCA) in serum was 245 EU/ml, and 67Ga scintigraphy showed marked accumulation in the abdomen. Abdominal angiography demonstrated a bead-like appearance and irregularities in the peripheral branches of the hapatic artery, the splenic artery, the cystic artery, and the superior mesenteric artery. Because of the high MPO-ANCA level and the angiographic abnormalities, MPO-ANCA-related vasculitis was diagnosed. She was treated with 1 g of methylprednisolone daily for 3 days, followed by 60 mg of prednisolone and 50 mg of cyclophosphamide daily. Her condition improved dramatically, and the MPO-ANCA level became almost normal. During treatment, her blood pressure rose markedly with a normal serum creatinine level and normal urinalysis. Plasma renin activity was 13.3 ng/ml/hr. Renal angiography showed stenoses and irregularities in the peripheral branches of renal arteries bilaterally. These findings led to a diagnosis of renovascular hypertension due to vasculitis. Her blood pressure was controlled with an angiotensin-converting enzyme inhibitor and a calcium antagonist. Vasculitis associated with chronic supportive lung disease has occasionally been reported, which suggests a casual relation between chronic respiratory infection and ANCA-related vasculitis. Systemic vasculitis should be taken into account as a potential complication of chronic suppurative lung disease.

Anti-Inflammatory Agents↗
PubMed1998

[Macrocytic anemia with anisocytosis due to alcohol abuse and vitamin B6 deficiency].

Megaloblastic anemia due to folic acid deficiency and ringed sideroblastic anemia have been reported in alcohol abusers. It has also been reported that vitamin B6 deficiency causes ringed sideroblastic anemia as well as microcytic anemia that is not associated with ringed sideroblasts. We encountered a case of macrocytic anemia with anisocytosis in a 75-year-old alcohol abuser who suffered vitamin B6 deficiency. Neither megaloblastic changes nor ringed sideroblasts were observed in specimens of the patient's bone marrow. Analyses of porphyrin content and heme biosynthetic enzyme activity suggested a decline in ALA-synthase activity (an enzyme that depends on vitamin B6) as well as decreased ferrochelatase activity or abnormal iron metabolism. Abstention from alcohol led to a reduction in mean corpuscular volume and the disappearance of Pappenheimer bodies commonly observed in the red blood cells of drinkers. Follow-up supplements of vitamin B6 resolved the patient's anisocytosis and anemia.

Aged↗
PubMed1998

[Rheumatoid nodule diagnosed by thoracoscopy using flexible fiberoptic bronchoscope].

A 51-year-old man had been treated at a nearby hospital since 1993 for rheumatoid arthritis. Right pectoralgia developed in December 1994, and the patient consulted a nearby hospital, which detected right pleural effusion retention was pointed out on chest x-ray films. The patient was referred and admitted to our hospital. Rheumatic pleurisy was suspected because of a high serum rheumatoid factor(RF)level and high RF and high rheumatoid arthritis hemagglutination levels in the pleural effusion. However, due to a high adenosine deaminase level in the pleural effusion tuberculous pleurisy could not be ruled out. After drainage through a trocar catheter, the thoracic cavity was examined by thoracoscopy through the site of catheter insertion. As a result, sporadic bluish white nodular lesions were observed on the pleura. Granuloma formations presenting a palisade arrangement of giant cells were also observed, and pathologically diagnosed as rheumatoid nodules, thus providing the basis for a diagnosis of rheumatic pleurisy. Treatment with an increased dose of prednisolone achieved a rapid remission of the pleural effusion. Our experience underscored the usefulness of thoracoscopy as a means diagnosing of rheumatic pleurisy.

Anti-Inflammatory Agents↗
PubMed1997

Rapid colorectal adenoma formation initiated by conditional targeting of the Apc gene.

Familial adenomatous polyposis coli (FAP) is a disease characterized by the development of multiple colorectal adenomas, and affected individuals carry germline mutations in the APC gene. With the use of a conditional gene targeting system, a mouse model of FAP was created that circumvents the embryonic lethality of Apc deficiency and directs Apc inactivation specifically to the colorectal epithelium. loxP sites were inserted into the introns around Apc exon 14, and the resultant mutant allele (Apc580S) was introduced into the mouse germline. Mice homozygous for Apc580S were normal; however, upon infection of the colorectal region with an adenovirus encoding the Cre recombinase, the mice developed adenomas within 4 weeks. The adenomas showed deletion of Apc exon 14, indicating that the loss of Apc function was caused by Cre-loxP-mediated recombination.

Adenomatous Polyposis Coli↗
PubMed1997

Neutrophil secondary-granule deficiency as a hallmark of all-trans retinoic acid-induced differentiation of acute promyelocytic leukemia cells.

Acute promyelocytic leukemia (APL) is a neoplasm with the unique chromosomal translocation t(15;17), which involves the retinoic acid receptor alpha gene. All-trans retinoic acid (ATRA) has been used for APL patients as a potent therapeutic agent to induce differentiation of leukemia cells. Although polymorphonuclear leukocytes (PMNs) appearing in the blood and bone marrow during ATRA treatment often possess Auer rods, indicating their neoplastic origin, other morphological abnormalities of PMNs have not been elucidated. We studied the morphological changes of APL cells during ATRA treatment at the ultrastructural level. Although most aberrant primary granules, including Auer rods, became morphologically normal in response to ATRA therapy and the nuclei showed chromatin condensation and lobulation, resulting in the emergence of PMNs, the lobulated nuclei often had nuclear filamentous connections and/or nuclear blebs, indicating some pathological process. Furthermore, PMNs, particularly early in ATRA treatment, lacked neutrophil secondary granules as did the PMNs appearing in a culture of APL cells incubated with ATRA, findings consistent with previously reported data that acute myeloid leukemia cell lines do not produce secondary granule proteins even after induction of differentiation towards mature neutrophils. The present data indicate that ATRA is incapable of inducing complete morphological maturation of APL cells and that secondary-granule deficiency may be a hallmark of aberrantly differentiated leukemic cells.

Adult↗
PubMed1997

Cytological detection of telomerase activity using an in situ telomeric repeat amplification protocol assay.

A previously reported highly sensitive assay for measuring telomerase activity on cell and tissue extracts indicates that most human tumor tissues, but not cells adjacent to tumors, have detectable telomerase activity. Although this assay has provided a significant amount of information about the presence or absence of telomerase activity, it does not indicate whether all cells within a tumor have telomerase activity or whether only a subset does. The present report demonstrates the ability to advance this technology to an in situ assay. Using fluorescent telomerase primers and in situ PCR, we show that telomerase activity can be detected at the cellular level. This study demonstrates that telomerase activity is not detected in normal cells but is detected in tumor cells of clinical specimens and in tumor-derived cell lines.

Acute Disease↗
PubMed1997

Stop and branch behaviors of geniculocortical axons: a time-lapse study in organotypic cocultures.

The behavior of growing thalamic axons was studied in an organotypic coculture of the lateral geniculate nucleus (LGN) with the visual cortex (VC) to reveal cellular interactions that underlie the formation of lamina-specific thalamocortical connections. The LGN explant was placed at the ventral side, pial surface, or lateral edge of the VC explant, and fluorescent dye-labeled LGN axons were observed by confocal microscopy in fixed and living tissue. The axonal projection pattern in fixed cocultures after 1 week in vitro demonstrated that, in all three configurations, LGN axons formed primitive branches mainly in layer 4. A time-lapse study further examined axonal growth and branch formation in the living cortical explant. The majority of branches emerged within layer 4 behind the axonal tip, regardless of the direction of axonal entry. In addition, most axons entering from the ventral or pial side of the VC exhibited a transient or persistent stop of axonal growth in and around layer 4, whereas those entering from the lateral edge of the VC traveled along layer 4 without exhibiting stop behavior. The axonal stop often was accompanied by growth cone collapse and a slight retraction. These results suggest the existence of branch and stop cues in layer 4 of the cortex that are recognized by LGN axons.

Animals↗
PubMed1997

The relationship between telomere length and therapy-associated cytogenetic responses in patients with chronic myeloid leukemia.

BACKGROUND: Chronic myeloid leukemia (CML) is a clonal disease with specific cytogenetic changes involving the Philadelphia (Ph) translocation. The authors examined the relationship between telomere length (terminal restriction fragment [TRF]) and therapy-associated cytogenetic responses in CML patients. METHODS: The authors examined the telomere length and telomerase activity in 44 patients with Ph-positive CML in the chronic phase. TRF was determined by Southern blot analysis using the (TTAGGG)4 probe and telomerase activity was assessed by the telomeric repeat amplification protocol and fluorescent-labeled primers. RESULTS: At the time of CML diagnosis, 19 patients had TRFs within the age-matched normal range (mean +/- 2 x standard deviation [SD]) and the remaining 25 patients had TRFs shorter than the age-matched normal range (< mean +/- 2 x SD). Hematologic findings, including leukocyte count, hemoglobin level, platelet count, and percentage of bone marrow blasts at the time of diagnosis did not significantly differ between patients with normal and shortened TRFs; however, those with shortened TRFs had high levels of telomerase activity (P = 0.045). In a group of patients treated with alpha-interferon (n = 32), those with normal TRFs had a significantly lower frequency of blast crises (P = 0.0328), a significantly higher incidence of cytogenetic responses (P = 0.0185), and a favorable prognosis (P < 0.01) compared with those with shortened TRFs. CONCLUSIONS: These findings suggest that normal TRFs in a small number of CML patients at the time of diagnosis may have a significant amount of normal stem cells remaining. The authors suggest that normal TRFs at the time of diagnosis indicate a subset of CML patients who may respond favorably to alpha-interferon therapy.

Adolescent↗
PubMed1997

Cloning and expression of cDNA encoding heart-type isoform of AMP deaminase.

Mouse cDNA for the heart-type (H) isoform of AMP deaminase (EC 3.5.4.6., AMPD) has been isolated and characterized. The cDNA for the Ampd gene expressed in heart is predicted to encode a peptide of 766 amino acids with a molecular mass of 88 kDa. The coding region of this cDNA was quite homologous to the human AMPD3 gene which encodes the erythrocyte-type (E) isoform of AMPD, although the H-isoform of rodent AMPD was reported to be immunologically distinct from the E-isoform of human AMPD. The non-coding region of the isolated cDNA is not homologous to human AMPD3, while rodent Ampd1 has similarity to human AMPD1 in the non-coding region as well as in the coding region. The transcripts for the cloned cDNA were expressed in heart, slow-twitch skeletal muscle and non-muscle tissues. Prokaryotic expression showed that this cDNA encodes a catalytically active enzyme which reacts to the specific antibody raised to the H-isoform of AMPD.

AMP Deaminase↗
PubMed1997

International scoring system for evaluating prognosis in myelodysplastic syndromes.

Despite multiple disparate prognostic risk analysis systems for evaluating clinical outcome for patients with myelodysplastic syndrome (MDS), imprecision persists with such analyses. To attempt to improve on these systems, an International MDS Risk Analysis Workshop combined cytogenetic, morphological, and clinical data from seven large previously reported risk-based studies that had generated prognostic systems. A global analysis was performed on these patients, and critical prognostic variables were re-evaluated to generate a consensus prognostic system, particularly using a more refined bone marrow (BM) cytogenetic classification. Univariate analysis indicated that the major variables having an impact on disease outcome for evolution to acute myeloid leukemia were cytogenetic abnormalities, percentage of BM myeloblasts, and number of cytopenias; for survival, in addition to the above, variables also included age and gender. Cytogenetic subgroups of outcome were as follows: "good" outcomes were normal, -Y alone, del(5q) alone, del(20q) alone; "poor" outcomes were complex (ie, > or = 3 abnormalities) or chromosome 7 anomalies; and "intermediate" outcomes were other abnormalities. Multivariate analysis combined these cytogenetic subgroups with percentage of BM blasts and number of cytopenias to generate a prognostic model. Weighting these variables by their statistical power separated patients into distinctive subgroups of risk for 25% of patients to undergo evolution to acute myeloid leukemia, with: low (31% of patients), 9.4 years; intermediate-1 (INT-1; 39%), 3.3 years; INT-2 (22%), 1.1 years; and high (8%), 0.2 year. These features also separated patients into similar distinctive risk groups for median survival: low, 5.7 years; INT-1, 3.5 years; INT-2, 1.2 years; and high, 0.4 year. Stratification for age further improved analysis of survival. Compared with prior risk-based classifications, this International Prognostic Scoring System provides an improved method for evaluating prognosis in MDS. This classification system should prove useful for more precise design and analysis of therapeutic trials in this disease.

Acute Disease↗
PubMed1997

A coiled-coil tetramerization domain of BCR-ABL is essential for the interactions of SH2-containing signal transduction molecules.

BCR-ABL is a chimeric oncoprotein that exhibits deregulated tyrosine kinase activity and is implicated in the pathogenesis of Philadelphia chromosome (Ph1)-positive leukemia. We have previously shown SH2-containing phosphotyrosine phosphatase SHP-2 forms stable complexes with BCR-ABL and Grb2 in BCR-ABL-transformed cells (Tauchi, T., Feng, G. S., Shen, R., Song, H. Y., Donner, D., Pawson, T., and Broxmeyer, H. E. (1994) J. Biol. Chem. 269, 15381-15387). To elucidate the structural requirement of BCR-ABL for the interactions with SH2-containing signaling molecules, we examined a series of BCR-ABL mutants which include the Grb2 binding site-deleted BCR-ABL (1-63 BCR/ABL), the tetramerization domain-deleted BCR-ABL (64-509 BCR/ABL), and the SH2 domain-deleted BCR-ABL (BCR/ABL deltaSH2). These BCR-ABL mutants were previously shown to reduce the transforming activity in fibroblasts. We found that the tetramerization domain-deleted BCR-ABL did not induce the tyrosine phosphorylation of SHP-2 and the interactions of BCR-ABL, SHP-2, and Grb2. In vitro kinase assays have also shown that the tetramerization domain-deleted BCR-ABL mutant did not phosphorylate GST-SHP-2 in vitro. SHP-2 was co-immunoprecipitated with phosphatidylinositol 3-kinase in BCR/ABL p210-transformed cells; however, this interaction was not observed in the tetramerization domain-deleted BCR-ABL mutant. Therefore the tetramerization domain of BCR-ABL is essential for interactions of these downstream molecules.

Cell Line↗
PubMed1997

Tc-99m-MIBI scintigraphy for detecting parathyroid adenoma and hyperplasia.

We performed scintigraphy with technetium-99m-methoxyisobutylisonitrile (MIBI) in 10 patients with parathyroid adenoma (7 lesions) or hyperplasia (9 lesions). Correlation between an amount of accumulation of MIBI and histological types of the lesions were evaluated with special reference to an amount of oxyphilic cell in the lesions. Selected lesions were also evaluated for mitochondrial density by electromicroscopy and showed increased mitochondrial density in the oxyphilic cells. All lesions equal to or above 220 mg showed positive scintigraphic results despite differences in cell types. Undetected lesions were all equal to or below 100 mg. The scintigraphic results for 2 lesions with abundant oxyphilic cells were both positive although those for 11 lesions with abundant chief cells only 6 were positive, probably because these lesions were smaller in the hyperplasia group. In conclusion, MIBI uptake in parathyroid lesions was not dependent on the cell type but either on the size or functional state of the lesions.

Adenoma↗
PubMed1997

Scan findings of various myocardial SPECT agents in a case of amyloid polyneuropathy with suspected myocardial involvement.

A 31-year-old male having familial amyloid polyneuropathy underwent a Tc-99m(V)-DMSA study to evaluate the myocardial involvement. The patient also underwent T1-201, I-123-BMIPP and I-123-MIBG myocardial SPECT studies to evaluate blood perfusion, fatty acid metabolism and sympathetic function of the heart, respectively. Tc-99m(V)-DMSA SPECT showed uptake to the myocardium indicating myocardial involvement of amyloidosis. Both T1-201 and I-123-BMIPP studies showed normal uptake indicating normal blood perfusion and fatty acid metabolism but I-123-MIBG SPECT showed no uptake to the heart, indicating severe impairment of sympathetic function.

3-Iodobenzylguanidine↗
PubMed1997

Neodymium:YLF picosecond laser segmentation for retinal traction associated with proliferative diabetic retinopathy.

PURPOSE: To determine the applicability of laser segmentation for severing fibrovascular tissue and hyaloid interfaces in the treatment of tractional complications of proliferative diabetic retinopathy. METHODS: A prototype neodymium:yttrium-lithium-fluoride (Nd:YLF) picosecond pulse photodisruptive laser was used in eight eyes (seven patients) with proliferative diabetic retinopathy as part of a Food and Drug Administration-approved phase 1 protocol. There were three indications for treatment: type I: distortion and shallow elevation of the macular caused by taut, adherent, posterior hyaloid interface (two eyes); type II: traction retinal detachment involving the fovea (two eyes); and type III: fovea-threatened, traction retinal detachment (four eyes). Traction release was accomplished by laser segmentation of the detached hyaloid interfaces and fibrotic, contracted proliferative tissue. The Nd:YLF uses low pulse energy (0.10 mJ, 1,000 pulses per second for 10 consecutive seconds) that allows tissue cutting near the retinal surface. RESULTS: Both type I eyes had relief of traction forces; visual acuity improved from 20/400 to 20/50 in one eye; the other remained stable. Of the two type II eyes, one had anatomic reattachment of the fovea with improvement in visual acuity (hand movements to 20/50); the second required vitrectomy. Of the four type III eyes, all had anatomic improvement; three maintained pretreatment acuity; the fourth eye developed vitreous hemorrhage at 6 months and underwent vitrectomy. Three treatments (two eyes) caused vitreous hemorrhage that resulted in a transient drop in acuity (1 to 2 lines). No patient developed a retinal break or choroidal hemorrhage. CONCLUSION: In a small pilot study, the Nd:YLF laser segmented proliferative tissue near the retinal surface and elevated hyaloid interfaces. In selected cases, this may enable flattening of traction retinal detachment or release of retinal distortion.

Adult↗
PubMed1997

The in vitro effects of all-trans-retinoic acid and hematopoietic growth factors on the clonal growth and self-renewal of blast stem cells in acute promyelocytic leukemia.

All-trans-retinoic acid (ATRA) has been used as a potent therapeutic agent to induce differentiation of acute promyelocytic leukemia (APL) cells, and granulocyte colony-stimulating factor (G-CSF) has been reported to enhance this effect of ATRA in vitro. We investigated the effects of ATRA and three myeloid growth factors, including G-CSF, on the growth of the leukemic stem cells of 10 APL patients. G-CSF was the most powerful stimulator of leukemic colony formation in five out of 10 patients, but was neither the major stimulant of self-renewal of the blast stem cells nor an inducer of maturation. In contrast, ATRA was highly effective in inducing morphological maturation of leukemic promyelocytes, but variable results were obtained in regard to its effects on the growth of blast stem cells: ATRA suppressed both clonal growth and self-renewal in some patients, but was inactive or even had stimulating effects in the other patients. Similar variable effects were observed with the combination of ATRA and G-CSF. These findings indicate that the differentiation-inducing effect of ATRA is not always associated with growth inhibition of leukemic stem cells in vitro and justify the use of chemotherapy in conjunction with ATRA in the treatment of APL.

Adolescent↗