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Biomedical subjects

T Fujimoto

Publications and source records attributed to T Fujimoto.

At least 37 records · Page 2Linked to original sources
PubMed2002

Lung herniation as an anatomic consequence of pneumonectomy.

BACKGROUND: Pneumonectomy causes an overdistention of the remaining lung as an adaptive response. Excessive lung herniation occasionally causes serious lung dysfunction. METHODS: Twenty-seven patients were selected from 152 patients who underwent pneumonectomy for lung cancer between 1990 and 1998. Complete resections were accomplished; no recurrence was observed for 3 years in these 27 patients. To evaluate the extent of herniation, the Lung Herniation Index (LHI) was developed and defined as the sum of proportions of the maximal transverse length of the remaining lung divided by the transverse length of the thoracic cavity, measured at the level of the aortic arch and the inferior pulmonary vein on chest computed tomography. Sequential changes in LHI were compared between groups. RESULTS: Changes in LHI did not differ between groups delineated on the basis of an FEV1 of 70 % (p = 0.45) and RV/TLC of 40 % (p = 0.99). Patients with a low body mass index (BMI) (< 20 kg/m(2)), however, showed a significantly greater degree of lung herniation than those with a high BMI (> or = 20 kg/m(2)) (p < 0.05). CONCLUSIONS: Concomitant COPD has no effect on lung herniation. Some preventive procedure should be considered for patients with low BMI.

Adult↗
PubMed2002

Focal segmental glomerulosclerosis in a case of panhypopituitarism: a possible role of growth hormone treatment.

Panhypopituitarism manifests various symptoms including growth failure, hypothyroidism, adrenal insufficiency and hypogonadism. Dwarfism is an important problem in children with this condition, and long-term treatment with recombinant human growth hormone (GH) is usually required. We report a 24-year-old man with panhypopituitarism complicated by focal segmental glomerulosclerosis (FSGS). The patient had been treated with GH for hypopituitary dwarfism from 3 years of age. Proteinuria was initially noticed at 15 years of age and persisted despite cessation of GH supplementation at 18 years of age. A renal biopsy specimen showed glomerular hypertrophy and limited glomerulosclerosis, compatible with FSGS. To our knowledge, this is the first reported case of panhypopituitarism complicated by FSGS. Our case suggests that GH treatment for dwarfism may induce irreversible glomerular disease.

Adult↗
PubMed2001

Developmental expression of a unique carbohydrate antigen, Tn antigen, in mouse central nervous tissues.

Using an anti-Tn monoclonal antibody, the Tn antigen was detected immunohistochemically in prenatal and early postnatal central nervous tissues. On embryonic day 9 (E9), the antigen was distributed throughout the single neuroepithelial layer in the neocortex and then became more prominent in the preplate than in the ventricular zone along with formation of the preplate. Following division of the preplate and concomitant formation of the cortical plate, distinct labeling of the neocortex occurred in the marginal, subplate and intermediate zones, whereas in the cortical plate and ventricular zone were virtually not immunostained. It is notable that thalamocortical afferent fibers were also immunostained specifically on E14. After birth, the localization of the antigen became less noticeable and by 3 weeks after birth, the antigen had substantially disappeared. In the developing cerebellum, prominent labeling was also observed in the molecular layer and outskirts of the cerebellar nuclei on early postnatal days. To characterize the glycoprotein bearing the Tn antigen biochemically, immunoblot analysis was performed. The glycoprotein, most of which was extracted with a salt solution, migrated as a broad smeared band corresponding to a molecular weight of about 250 kDa on SDS-PAGE. Among the various tissues examined, this glycoprotein was only detected in the brain and its amount increased until an early postnatal stage with a peak on postnatal day 3 (P3), and then decreased gradually with age. This spatially and developmentally regulated expression of the Tn antigen suggests that this antigen plays a significant role in brain development.

Afferent Pathways↗
PubMed2001

Mutations in the mitotic check point gene, MAD1L1, in human cancers.

Aneuploidy is a characteristic of the majority of human cancers, and recent studies suggest that defects of mitotic checkpoints play a role in carcinogenesis. MAD1L1 is a checkpoint gene, and its dysfunction is associated with chromosomal instability. Rare mutations of this gene have been reported in colon and lung cancers. We examined a total of 44 cell lines (hematopoietic, prostate, osteosarcoma, breast, glioblastoma and lung) and 133 fresh cancer cells (hematopoietic, prostate, breast and glioblastoma) for alterations of MAD1L1 by RT-PCR-SSCP and nucleotide sequencing. Eight mutations consisting of missense, nonsense and frameshift mutations were found, together with a number of nucleotide polymorphisms. All the alterations in cell lines were heterozygous. Frequency of mutations was relatively high in prostate cancer (2/7 cell lines and 2/33 tumor specimens). We placed a mutant truncated MAD1L1, found in a lymphoma sample, into HOS, Ht161 and SJSA cell lines and found that it was less inhibitory than wild type MAD1L1 at decreasing cell proliferation. Co-expression experiments showed that the mutant form had a dominant-negative effect. Furthermore, this mutant impaired the mitotic checkpoint as shown by decreased mitotic indices in HOS cells expressing mutant MAD1L1 after culture with the microtubule-disrupting agent, nocodazole. Our results suggest a pathogenic role of MAD1L1 mutations in various types of human cancer.

Breast Neoplasms↗
PubMed2001

Tumor necrosis factor alpha polymorphism associated with increased susceptibility to development of adult T-cell leukemia/lymphoma in human T-lymphotropic virus type 1 carriers.

Human T-lymphotropic virus type 1 (HTLV-1) is etiologically associated with adult T-cell leukemia/lymphoma (ATL). Nevertheless, most individuals infected with HTLV-1 do not develop ATL. To attempt to identify genetic factors promoting the progression to ATL, we investigated in HTLV-1 carriers the relationship between susceptibility to ATL and several polymorphisms: the three "decreased-detoxifying" polymorphisms in GSTM1, GSTT1, and CYP1A1, the "proapoptotic" polymorphism in BCL2, and the five "high-production" polymorphisms in tumor necrosis factor alpha (TNF-alpha) using PCR-based genotyping assays. ATL patients (n = 71) were younger than HTLV-1 carriers (n = 80; 57 +/- 12 versus 63 +/- 10 years; P = 0.0017). MALE:female ratio in ATL patients was higher than in carriers (52:19 versus 19:61, respectively; P < 0.0001), probably reflecting a higher incidence of HTLV-1 infection in females and a higher incidence of development of ATL in males. We found that the frequency of the TNF-alpha-857T allele, reported to be associated with high transcriptional activity of the promoter/enhancer region of the TNF-alpha gene, was enriched in individuals with ATL compared with healthy carriers (18.3% versus 8.8%, respectively; odds ratio, 2.34; 95% confidence interval, 1.2-4.7). None of the other four TNF-alpha polymorphisms was a significant indicator of risk of development of ATL, although odds ratios (ATL versus carrier) of all of the TNF-alpha polymorphisms were higher than 1.0. Furthermore, analysis of polymorphisms for GSTM1, GSTT1, CYP1A1, and BCL2 showed no significant difference between ATL patients and healthy carriers. Genetic polymorphism leading to increased TNF-alpha production may enhance susceptibility to ATL among HTLV-1 carriers. Alternatively, but less likely, the HLA loci might be an important factor because the TNF-alpha gene lies within the class III region of the MHC; however, the 857T allele is not in linkage disequilibrium with HLA alleles associated with ATL development.

Carrier State↗
PubMed2001

Caveolin-2 is targeted to lipid droplets, a new "membrane domain" in the cell.

Caveolin-1 and -2 constitute a framework of caveolae in nonmuscle cells. In the present study, we showed that caveolin-2, especially its beta isoform, is targeted to the surface of lipid droplets (LD) by immunofluorescence and immunoelectron microscopy, and by subcellular fractionation. Brefeldin A treatment induced further accumulation of caveolin-2 along with caveolin-1 in LD. Analysis of mouse caveolin-2 deletion mutants revealed that the central hydrophobic domain (residues 87-119) and the NH(2)-terminal (residues 70-86) and COOH-terminal (residues 120-150) hydrophilic domains are all necessary for the localization in LD. The NH(2)- and COOH-terminal domains appeared to be related to membrane binding and exit from ER, respectively, implying that caveolin-2 is synthesized and transported to LD as a membrane protein. In conjunction with recent findings that LD contain unesterified cholesterol and raft proteins, the result implies that the LD surface may function as a membrane domain. It also suggests that LD is related to trafficking of lipid molecules mediated by caveolins.

Animals↗
PubMed2001

Diastereoselective tandem Michael-intramolecular Wittig reactions of a cyclic phosphonium ylide with 8-phenylmenthyl enoates.

The diastereoselective tandem Michael-intramolecular Wittig reactions of a five-membered cyclic phosphonium ylide 2 using 8-phenylmenthyl enoates were examined. The reaction of the phosphonium ylide with 8-phenylmenthyl cinnamate followed by the hydrolysis of the resulting enol ether 4a afforded (3R,4S)-4-(diphenylphosphinyl)-3-phenylcycloheptanone (3R,4S)-5a as the major isomer. The diastereoselectivity of the initial tandem reactions was estimated to be 94:6 from the 31P NMR of a mixture of the diastereomeric ketal derivatives 6a and 6'a which were obtained by the reaction of 5a with (2R,3R)-2,3-butanediol, and the absolute configuration of the major isomer was determined by the single-crystal X-ray analysis. Similar reactions using some 8-phenylmenthyl alkenoates were attempted. As a result, it was clarified that the corresponding trans-ketones 5b-d were obtained and that the diastereomer ratios of their ketal derivatives were 60:40-73:27.

Journal Article↗
PubMed2001

Neurogenic bladder in Lambert-Eaton myasthenic syndrome and its response to 3,4-diaminopyridine.

Autonomic dysfunction, as well as neuromuscular involvement, is a common manifestation of Lambert-Eaton myasthenic syndrome (LEMS). Dry mouth and impotence have been described as typical features of autonomic dysfunction, but neurogenic bladder is infrequent or subclinical in LEMS. We report a patient with neurogenic bladder secondary to LEMS whose condition responded to 3,4-diaminopyridine (3,4-DAP). In this patient's serum, results of repeated measurement with P/Q-type VGCC antibodies proved positive, but not with N-type VGCC and synaptotagmin antibodies. A review of the literature turned up a few patients with voiding dysfunction related to LEMS, but no urodynamic studies were done on these patients. Ours is the first case in which 3,4-DAP was efficacious in treating LEMS and neurogenic bladder. Responses of 3,4-DAP in urodynamic studies suggest that in this LEMS patient neurogenic bladder was caused by defective neurotransmission both in the autonomic detrusor and skeletal abdominal muscles.

4-Aminopyridine↗
PubMed2001

Different distribution of c-myc and MIB-1 positive cells in malignant meningiomas with reference to TGFs, PDGF, and PgR expression.

We investigated the expression of transforming growth factors (TGFs), platelet-derived growth factor (PDGF), progesterone receptor (PgR), and c-myc in 20 cases of meningioma of various grades: 17 benign, 2 atypical, and 1 anaplastic. All cases of atypical and anaplastic meningioma were positive for c-myc, whereas all 17 benign meningiomas were negative for c-myc immunostaining. Expression of TGF-alpha, TGF-beta, and PDGF-BB proteins was seen in more than 80% of the meningioma cases and was not restricted to their histological grade of meningioma. PgR was expressed mainly in benign meningiomas. Moreover, the cells expressing c-myc protein were not usually stained by MIB-1. These results indicate that c-myc does not directly work on the proliferation of meningioma cells, and even in homogeneous meningioma cells, there may be many functional variations that lead the meningioma cells to their growth.

Aged↗
PubMed2001

Multiple thymoma with myotonic dystrophy.

A case of multiple thymoma associated with myotonic dystrophy is reported. The patient was a 42-year-old man who had two separate encapsulated thymoma in the anterior mediastinum, at 3 cm in diameter on the right side, and at 4 cm in diameter on the left. Extended thymo-thymomectomy was performed. Microscopically, the tumor in the right thymic lobe was predominantly mixed type, and that in the left predominantly epithelial type. Neuromuscular disease appeared to develop, with severe sputum retention in the larynx and he was referred to neurology at 6 months after surgery. On examination, he presented a characteristic hatchet face, muscle atrophy, muscle weakness, percussion myotonia and grip myotonia, and diagnosis was revised to be multiple thymoma associated with myotonic dystrophy. This association is extremely rare. It is difficult to clarify whether this association was a syndrome or coincidence.

Adult↗
PubMed2001

Two novel gene mutations in type I antithrombin deficiency.

We studied the molecular basis of type I antithrombin (AT) deficiency in 2 Japanese families, in which affected persons had histories of recurrent venous thrombosis and low (about 50% of normal) levels of AT protein according to measurements by both functional and antigen assays. Southern blotting of DNA isolated from peripheral leukocytes revealed no abnormalities in all the cases examined. Direct sequencing of the polymerase chain reaction (PCR) products from case I suggested a novel heterozygous nonsense mutation in exon 4 (GAG-->TAG at nucleotide position 7627, leading to Glu306 stop). The sequencing of the subclones of the patient's exon 4 products confirmed the nonsense mutation. No other sequence abnormalities were detected in the rest of the PCR products. The same mutation was detected in this patient's brother, who had a history of recurrent venous thrombosis and a reduced level of AT activity. In case 2, the direct sequencing of PCR products suggested a novel heterozygous 9-bp deletion in exon 3a (-CACTTC at nucleotide position 5354-5362, leading to the deletion of 3 amino acids, His120, Phel21, and Phe122). The 9-bp deletion mutation in the region of a unique quasi palindrome was confirmed by sequencing several of the subclones of the patient's exon 3a from the PCR products. No other mutations were found by direct sequencing of the rest of the coding regions. The 2 mutations found in this study are novel. The use of PCR and the sequencing of the PCR product subclones has simplified and confirmed the detection and characterization of the various AT mutations.

Adult↗
PubMed2001

Focal eosinophilic myositis.

Idiopathic hypereosinophilic syndrome (HES) is a heterogeneous group of disorders with the common features of prolonged eosinophilia of underdetermined cause and multiple organ system dysfunction. Focal eosinophilic myositis is an uncommon manifestation of HES. We report a case of focal eosinophilic myositis with tender muscle swelling followed by proximal weakness, but without non-systemic symptoms and muscle trophism in the lower limbs. Muscle biopsy specimen showed acute myositis with eosinophil infiltration. Electromyographic features were typical of myositis. The clinical and biochemical response to corticosteroids was excellent, and a relapse that occurred because the steroid dose was not lowered, responded well.

Adult↗
PubMed2001

Cytokines and cell cycle regulation in the fibrous progression of crescent formation in antiglomerular basement membrane nephritis of WKY rats.

Cytokines may regulate cell proliferation by cell-cycle-regulatory proteins, in which cyclin-dependent kinase inhibitors (CDKI) inhibit cell proliferation. We investigated whether CDKI p21 or p27, both of which are potentially regulated by transforming growth factor (TGF)-beta, a key cytokine in fibrogenesis, are involved together with TGF-beta and/or platelet-derived growth factor (PDGF) in the fibrous progression of glomerular crescent formation and examined the sequential change in the cell type and the cellular background of myofibroblasts in crescent formation. Crescentic glomerulonephritis (GN) was induced by i.v. injection of rabbit antirat glomerular basement membrane antiserum in WKY rats. Animals were killed 1, 2, 3 and 4 weeks after the induction of GN, and their kidneys were processed for immunohistochemical examination. After 1 week more than 85% of glomeruli showed cellular crescents, which became fibrocellular with decreased cellularity by 4 weeks. ED 1-positive macrophages were components of crescent cells in about 44% at 1-2 weeks, and this proportion declined markedly afterwards. Alpha smooth muscle actin (alpha SMA, a marker for myofibroblasts)-positive cells were found in Bowman's epithelial cells (BEP) and in some crescent cells at 1 week, becoming major components of crescent cells by 4 weeks (about 40%). It was 2 weeks before invasion of alpha SMA-positive interstitial cells into glomeruli was evident. PDGF-B and PDGF receptor beta-positive cells, indicating possible targets for PDGF, were found in BEP adjoining crescent formation almost exclusively from 1 to 2 weeks. By contrast, both TGF-beta receptor types I- and II-positive cells, indicating possible effectors for TGF-beta, were found in BEP and crescent formation, and the percentage of these in the crescent formation did not change until 4 weeks (about 32%). Cells with positive immunostaining for proliferating cell nuclear antigen and cyclin A, markers for cell proliferation, in the crescent formation peaked in number and proportion at 1-2 weeks, then decreased. In contrast, cells with positive immunostaining for p21 and p27, CDKI, were sparse at 1 week, and then increased markedly in number and in proportion, peaking at 3 (39.6%) or 2-3 weeks (about 25-30%), respectively. The present study demonstrates that restrained expression or a transient increase in p21 and p27 may be associated with proliferation or with inhibited proliferation of crescent cells, most of which are macrophages and myofibroblasts. The action, of PDGF and TGF-beta may contribute to the recruitment of myofibroblasts into the crescent. The action of TGF-beta on crescent cells might be linked to the expression of p21 and/or p27.

Actins↗
PubMed2001

Hyperbaric hyperoxia suppresses growth of Staphylococcus aureus, including methicillin-resistant strains.

PURPOSE: We investigated the effects of increased oxygen tension on the in vitro growth of Staphylococcus aureus (MRSA), methicillin-sensitive Staphylococcus aureus (MSSA), and Escherichia coli (E. coli). METHODS: The effects of oxygen tension [normobaric normoxia (21% O(2) at 1 atm), normobaric hyperoxia (100% O(2) at 1 atm), hyperbaric normoxia (21% O(2) at 2 atm), and hyperbaric hyperoxia (100% O(2) at 2 atm) on the in vitro growth of MRSA, MSSA, and E. coli were investigated by population analysis. RESULTS: Compared with normobaric normoxia, a 90-min exposure to hyperbaric hyperoxia significantly inhibited growth of both MRSA (by 25.0 +/- 3.0%, mean +/- SEM; P < 0.01) and MSSA (by 24.0 +/- 3.3%; P < 0.01). Normobaric hyperoxia and hyperbaric normoxia were without effect. In contrast, the growth of E. coli was not affected by any of the above treatments. CONCLUSION: Our results indicate that the bacterium S. aureus, including resistant strains, is susceptible to oxygen stress. The observation that relatively brief (90-min) treatment with hyperbaric hyperoxia is sufficient to produce significant growth inhibition suggests that hyperbaric hyperoxia may be useful in the treatment of serious staphylococcal infections.

Journal Article↗
PubMed2001

Primary Sjögren's syndrome presenting as hypokalaemic periodic paralysis and respiratory arrest.

We report a case of hypokalaemic, flaccid quadriparesis with sudden respiratory arrest in a 27-year-old Japanese woman in whom the discovery of distal renal tubular acidosis led to the diagnosis of primary Sjögren's syndrome (SS). Hypokalaemic periodic paralysis as the initial manifestation of primary SS is rare, but when it occurs it may precede symptoms of xerostomia and xerophthalmia. The diagnosis of primary SS should be considered in premenopausal women who present with rapidly progressive weakness and hypokalaemia. with or without the sicca complex.

Adult↗
PubMed2001

Current strategy for surgical management of bronchiectasis.

BACKGROUND: There are few current reports of surgical management for bronchiectasis because of its decline in prevalence, and it remains controversial as to which subgroups of patients would benefit from surgical management. METHODS: We reviewed the medical records of all patients who underwent surgical resection for bronchiectasis between January 1, 1990, and December 31, 1997, at our hospital. RESULTS: Ninety patients underwent 92 operations for bronchiectasis. The mean age was 44.7 years. The presenting symptoms were productive cough in 82 patients, fever in 47 patients, hemoptysis in 35 patients, chest pain in 6 patients, and dyspnea on effort in 4 patients. The disease was bilateral in 13 patients. Complete resection was achieved in 75 patients. There was no operative mortality, and the morbidity rate was 19.6%. Postoperatively the patients were asymptomatic in 45.6%, improved in 38.0%, and showed no improvement in 16.4%. Logistic regression extracted the type of bronchiectasis, the existence of sinusitis, and the type of resection for prognostic discrimination with statistical significance. CONCLUSIONS: Surgery for bronchiectasis can be performed with acceptable morbidity and mortality. Patients with cylindrical bronchiectasis are good surgical candidates and chronic sinusitis is a risk factor for surgical resection. Complete resection should be done whenever possible.

Adolescent↗
PubMed2001

Involvement of disregulated c-myc but not c-sis/PDGF in atypical and anaplastic meningiomas.

We investigated the expression of c-myc and c-sis/PDGF mRNA and protein products in 20 cases of meningiomas of various grades: 10 benign, 5 atypical and 5 anaplastic meningiomas. All cases of atypical and anaplastic meningiomas were positive for c-myc protein and mRNA by immunohistochemistry and in situ hybridisation, respectively, while all 10 benign meningiomas were negative for c-myc immunostaining, with only one benign tumour positive for c-myc mRNA. Expression of PDGF-BB protein and c-sis mRNA were seen in more than 80% of the meningioma cases and was not restricted to the histological grades of meningiomas. Semiquantitative analysis showed that the frequency of c-myc immunopositive cells positively correlated with Ki-67 proliferative indices. Our findings suggest that c-myc, but not c-sis/PDGF, has some concern to the malignancy of meningiomas.

Adult↗