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Biomedical subjects

T Fujisawa

Publications and source records attributed to T Fujisawa.

At least 307 records · Page 17Linked to original sources

[A case of foreign body granuloma].

A 45-year-old man referred to our hospital complaining of dry cough. Chest X-ray and CT scan film indicated tumor shadow in the right anterior mediastinum. Although preoperative diagnosis was teratoma, the specimen extirpated by thoracotomy revealed macroscopically and microscopically foreign body granuloma originated from gauzes. He had undergone segmentectomy of right upper lobe for tuberculosis 28 years ago, so the gauzes were thought to be left in right thoracic cavity at the operation. The foreign body granuloma originated from gauzes are iatrogenic and few cases were reported previously, however, whirl like pattern demonstrated by MRI is retrospectively considered to be an important diagnostic finding in this case.

Granuloma, Foreign-Body↗

[Establishment of anti-idiotype monoclonal antibodies to human anti lung cancer monoclonal antibody (4G12)].

The object of this study is to establish anti-idiotype (anti-ID) monoclonal antibodies (MoAbs) against a human MoAb (4G12) that highly reacts with lung squamous cell carcinomas. Two murine anti-ID MoAbs (2H1 and 2B12) were established by hybridoma technology. They showed specific reactivity with 4G12 but not with 3H12 human MoAb, human IgM and human IgG. These two MoAbs demonstrated more than 90% of binding inhibition of 4G12 to lung squamous cell cancer cell line (PC10). Moreover, cross inhibition test showed that 2H1 and 2B12 detect different idiotypes of 4G12 each other. Furthermore, specific reactivity of anti 2H1 and anti 2B12 sera to PC10 were observed by cell binding ELISA. These two anti-ID MoAbs had internal image of the original antigen.

Animals↗

Presence of eight distinct homeobox-containing genes in cnidarians.

Using the polymerase chain reaction, we identified four different homeobox-containing genes in Hydra magnipapillata. Three of them, cnox1-Hm, cnox2-Hm and cnox4-Hm, were equivalent to homeobox genes that had already been identified in other species of cnidarians. cnox5-Hm was a new homeobox gene and was very similar to Mox1 in the mouse. Together with the published data, our results indicate that there are at least eight distinct classes of homeobox genes in cnidarians. These homeobox genes show a maximum of 60 to 77% identity in terms of the amino acid residues in their homeodomains to certain classes of homeobox genes that have been identified in Drosophila.

Amino Acid Sequence↗

Mutations can cause large changes in the conformation of a denatured protein.

Deletion of 13 amino acids from the carboxyl terminus of staphylococcal nuclease (WTSNase delta) results in a denatured, partially unfolded molecule that lacks significant persistent secondary structure but is relatively compact and monomeric under physiological conditions [Shortle & Meeker (1989) Biochemistry 28, 936-944; Flanagan et al. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 748-752]. Because of these and other properties of the SNase delta polypeptide, it is a useful model system for investigating the conformation of the denatured state of a protein without using extreme temperature or solvent conditions. Moreover, since the modification is a carboxyl-terminal deletion, SNase delta may also resemble a transient state of the polypeptide chain as it emerges from a ribosome prior to its folding. In the present study, we have examined the sizes and conformations of mutated forms of SNase delta, using small-angle X-ray scattering and circular dichroism spectroscopy. Seven mutated forms were studied: four with single substitutions, two with double substitutions, and one triple substitution. When present in the full-length SNase, each of these mutated forms exhibited unusual behavior upon solvent or thermal denaturation. In the case of the truncated form (SNase delta), the small-angle scattering curves of the mutated forms fall into two classes: one resembling the scattering curve of compact native nuclease and the other having features consistent with those expected for an expanded coil-like polymer. In contrast, the scattering curve of WT SNase delta exhibits features intermediate between those observed for globular proteins and random polymers. The amino acid substitutions that gave rise to compact, native-like versions of SNase delta were all of the m--type (m-substitutions are predicted to decrease the size of the denatured state). Those which gave rise to versions of SNase delta that were more extended and coil-like than WT SNase delta were of the m+ type (m+ substitutions are predicted to increase the size of the denatured state). Estimates of the residual secondary structure present in WT SNase delta, as well as both the m+ and m-substituted versions of SNase delta, as determined by CD, suggest that the formation of secondary structure and compaction of the polypeptide chain occur concurrently. Our results show that single amino acid substitutions can radically alter the conformational distribution of a partially condensed polypeptide chain.(ABSTRACT TRUNCATED AT 400 WORDS)

Algorithms↗

A single chain 19-kDa fragment from bovine thrombospondin binds to type V collagen and heparin.

Location of the type V collagen-binding domain within bovine thrombospondin (TSP) was investigated by using fragments of reduced and alkylated TSP. A fragment of relative molecular mass (19 kDa) was isolated, which inhibited binding of 125I-TSP to type V collagen in a solid-phase binding assay. A direct binding assay using the 125I-labeled fragment confirmed that the fragment actually bound to collagen. The fragment retained specificity for the native structure of type V collagen like the intact TSP molecule. Its binding to the collagen, however, was not inhibited by Ca2+ in contrast to intact TSP. Amino acid sequence analysis of the 19-kDa fragment suggested that this fragment corresponded to Val333-Lys412, a part of the stalklike region in the human TSP primary structure. It was found that the fragment also bound well to heparin in a specific and saturable manner and, furthermore, binding to type V collagen was inhibited by soluble heparin. Removal of the N-linked sugar chain from this fragment resulted in a 14-kDa fragment. The deglycosylated fragment retained the ability to bind to type V collagen as well as heparin. These results suggest that a type V collagen-binding site is present in the 80-residue portion of bovine TSP (Val333-Lys412) and is likely to be identical or lie very close to a heparin-binding site, which exists in the type I repeat structure.

Amino Acid Sequence↗

MHC-linked diabetogenic gene of the NOD mouse: molecular mapping of the 3' boundary of the diabetogenic region.

To localize and characterize the MHC-linked diabetogenic gene of the NOD mouse, we studied the class III region of the MHC in the NOD mouse and related strains. Hsp70, Bat5, Tnfa and Tnfb loci were studied by microsatellite polymorphism analysis and/or restriction mapping. The CTS mouse had the same allele as the NOD mouse at the Hsp70 locus, but different alleles at the Bat5, Tnfa and Tnfb loci from those of the NOD mouse. Our previous studies indicated that in the CTS mouse, class II MHC was the same as that of the NOD mouse, but that class I MHC was different at both K and D loci, and that CTS MHC was diabetogenic in the presence of NOD background genes. These data map major genetic susceptibility to type 1 diabetes to the segment flanked by class I K and class III Bat5 loci. Moreover, since the diabetogenic effect of the CTS MHC is weaker than that of the NOD MHC, these data suggest the presence of a second MHC-linked gene or gene complexes that modulate susceptibility to type 1 diabetes outside this segment.

Animals↗

Dose study of the immunosuppression of FK 506 in canine lung allo-transplantation.

The immunosuppressive effect of FK506 (FK) in comparison to cyclosporine A (CsA) on lung graft rejection was demonstrated using 24 mongrel dogs with left lung allotransplantation. The cytotoxic activity of peripheral blood mononuclear cells was evaluated using donor skin fibroblasts. In eight dogs not given immunosuppression, the grafted lungs lost aeration 5-10 days postoperatively, and histologic findings revealed grade II rejection and cytotoxic activity elevated to between 10.7 and 60.5%, being an average of 31.2% at an effector/target (E/T) ratio of 50. Of 12 dogs treated with FK, none demonstrated a cytotoxic activity of 10% or more at an E/T ratio of 50. Moreover, histologic examinations of the specimens obtained by open chest biopsy revealed no signs of rejection during the first 10 postoperative days of FK administration, except in one dog showing grade I rejection from the FK 0.05 mg/kg group. A dose study of the duration until the onset of graft rejection and the elevation of cytotoxic activity after the termination of FK administration revealed approximately 1-2 weeks in the FK 0.05 mg/kg group, 3-4 weeks in the 0.1 mg/kg group, and later in the 0.4 mg/kg and 2.0 mg/kg groups. However, severe body weight loss was seen in the 0.4 mg/kg and 2.0 mg/kg groups postoperatively, without recovery even after the termination of FK. In fact, two dogs died of pneumonia possibly derived from general emaciation. These results suggest the optimal concentration of FK in canine lung allo-transplantation to be 0.1 mg/kg intramuscularly.

Animals↗

The effect of exercise on fructose absorption.

The effect of exercise on intestinal absorption of fructose was evaluated in 10 subjects after they consumed four beverages, each containing a total of 50 g carbohydrate: 100% fructose (100F), 95% fructose and 5% glucose (95F), 70% fructose and 30% glucose (70F), and 100% glucose (100G), as well as a water placebo. With 100F and 95F, breath hydrogen, which is an index of incomplete absorption, increased significantly in all subjects. In contrast, hydrogen excretion did not increase in any subject after consumption of 100G or water, or in five of seven subjects who consumed 70F. The rapid increase in hydrogen excretion observed when consumption of 100F was followed by exercise was not noted during a comparable nonexercise trial. These data suggest that intestinal capacity for absorption of fructose is readily saturated after ingestion of amounts as small as 50 g and that exercise, which reduces intestinal transit time, can cause incomplete absorption of fructose.

Fructose↗

Fructose absorption.

Fructose found in modern diets as a constituent of the disaccharide sucrose is absorbed by a well-characterized absorptive system integrating enzymatic hydrolysis of the disaccharide and transfer of the resulting two monosaccharides through the apical membrane of the epithelial cell. The increasing use of high-fructose syrups and crystalline fructose prompted new studies aimed at the determination of the absorptive capacity for free fructose in the human gut. Results indicate that the capacity for fructose absorption is small compared with that for sucrose and glucose and is much less than previously estimated. The unexpected finding that the simultaneous ingestion of glucose can prevent fructose malabsorption suggests that the pair of monosaccharides might be absorbed by the disaccharidase-related transport system as if they were the product of the enzymatic hydrolysis of sucrose. This absorptive mechanism might not be able to transport fructose when ingested without glucose.

Animals↗

[The effect on age for the relationship between hypertension and glucose intolerance].

Recently, high frequencies of glucose intolerance and insulin resistance have been reported in patients with hypertension. However, both blood pressure and glucose tolerance are influenced by age. To investigate the effect of age on the interaction between blood pressure and glucose tolerance, we analyzed blood pressure and glucose tolerance in otherwise healthy subjects (n = 576) who underwent an oral glucose tolerance test and blood pressure measurement as a part of a healthy care program. The prevalence of DM and IGT were significantly higher in the hypertensive group than in the normotensive group. When the subjects were divided into three groups according to their age (less than 50 years old, between 50 and 60 years old and more than 60 years old), the prevalence of glucose intolerance (DM or IGT) was significantly higher in the hypertensive group than in the normotensive group in subjects under 50 years old, but not in subjects between 50 and 60 years old or over 60 years old. In the subjects classified as having normal glucose tolerance, the incremental area of glucose under the curve of 75g-OGTT was significantly higher in the hypertensive group than in the normotensive group. These data suggest that hypertension is associated with glucose intolerance in Japanese population and that age significantly affects this interaction.

Aged↗

[Eosinophil and neutrophil degranulation in allergic inflammation: immunohistochemical localization of granule proteins in fatal asthma and stimulus-dependent degranulation in vitro].

Airway inflammation is a central feature of bronchial asthma. The eosinophil, a major infiltrating cell in the airway wall in asthma, expresses its effector function by degranulation of toxic granule proteins. The role of the neutrophil in allergic inflammation is still controversial. In order to clarify the possible involvement of degranulation in allergic inflammation, we studied the immunohistochemical localization of granule proteins of the eosinophil and the neutrophil, namely, major basic protein (MBP) and elastase, respectively, in the lungs from patients with fatal asthma. We found that extracellular deposition of MBP or elastase coexisted with epithelial damage in the airway and that more eosinophils were found in slow onset fatal asthma cases and more neutrophils in sudden onset fatal asthma. These results suggest that inflammatory cell degranulation may have induced tissue injury in cases of fatal asthma, and that there may be two pathologically distinct forms of fatal asthma in terms of involvement of eosinophils or neutrophils. Next we showed that IgA and IgG coupled to Sepharose beads induced eosinophil and neutrophil degranulation. IgA and secretory IgA (sIgA) for neutrophils and sIgA for eosinophils were the most potent stimulators of degranulation. Pretreatment of eosinophils with pertussis toxin (PTX) for 2 h irreversibly abolished sIgA-induced degranulation, whereas PTX treatment only transiently inhibited IgG-induced eosinophil degranulation. Activated PTX catalyzed the in vitro ADP ribosylation of 41- and 44-kDa proteins in eosinophils. A 2-h pretreatment of intact cells with PTX markedly reduced the pools of unmodified 41- and 44-kDa substrates available for subsequent ADP-ribosylation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[A case of polypoid bronchial neurofibroma originating from right B2b successfully treated by bronchoscopic snaring forceps and Nd-YAG laser therapy].

A 34-year-old man with persistent cough was admitted to our hospital. Bronchoscopic examination revealed a polypoid tumor with smooth surface which almost completely obstructed the right main bronchus. The tumor was removed by transbronchial snaring forceps and histologically confirmed as neurofibroma. Residual tumor was excised by biopsy forceps and further endoscopic Nd-YAG laser vaporization was performed. This is the first case in our country in which bronchoscopic treatment was performed for bronchial neurofibroma. Bronchoscopic removal might be the preferred treatment in the present case, although long-term follow-up is also required.

Adult↗

[Influence of thoracotomy and partial lung resection on pulmonary function: comparison with median sternotomy].

The influence of thoracotomy on respiratory function was examined in 49 patients: 22 with intercostal thoracotomy without lung resection (ICT), 11 with partial lung resection (PLR) and 16 with median sternotomy (MST). Respiratory function (FVC, FEV1.0 and FEV1.0%) was measured preoperatively, in the early stage (14 days) and in the stable stage (after 3 months) postoperatively. In each group, the FVC and FEV1.0 were decreased to 70-80% of preoperative respiratory function in the early stage and rose to 90-95% in the stable stage. There were no significant differences among the groups. FEV1.0% did not vary in the different stages in any of the three groups. The ICT group was classified according to the type of skin incision (axillary incision (AI), anterolateral incision (ALI) and posterolateral incision (PLI)). FVC and FEV1.0 in the ALI subgroup were higher (p < 0.05) than in the PLI subgroup in the early stage. These results suggest that the selection of the skin incision is important for preserving respiratory function.

Adult↗

Propolypeptide and mature portions of von Willebrand factor of bovine origin recognize different sites on type-I collagen obtained from bovine tendon.

We compared the binding of propolypeptide and mature portions of von Willebrand factor of bovine origin to fibrillar type-I collagen obtained from bovine tendon. The propolypeptide (pp-vWF) and the mature portion (m-vWF) of human origin consist of 741 and 2050 amino acids, respectively, and are rather large proteins. The collagen-binding properties of the two proteins of bovine origin were similar in that both bound more avidly to native collagen than to heat-denatured collagen. Bindings was affected similarly by ionic strength but was not modified either by divalent cations or a synthetic peptide containing Arg-Gly-Asp. However, the binding sites in the fibrillar type-I collagen molecule for pp-vWF and m-vWF seem to be different: the two proteins did not effectively compete with each other for binding to collagen. Furthermore, pepsin treatment of fibrillar type-I collagen resulted in a drastic decrease in the binding of pp-vWF, while only a moderate decrease in the binding of m-vWF was observed after the treatment.

Amino Acid Sequence↗

Factors influencing survival after endoscopic Nd:YAG laser surgery for unresectable advanced malignancies of the trachea.

The effects of endoscopic Nd:YAG laser surgery were studied in 36 patients with unresectable advanced primary and metastatic malignancies in the trachea with special reference to the factors influencing long-term survival. Overall effectiveness of YAG laser treatment was demonstrated in 34 of the 36 patients (94 per cent), while the overall 1, 3 and 5 year survival rates after the first laser treatment were 25 per cent, 13 per cent and 13 per cent, respectively. Neither histologic type nor the severity of clinical symptoms before laser treatment showed any significant influence on the survival curves, however, endoscopic findings of stenosis, the effect of laser treatment and irradiated longitudinal length were all significantly correlated with the survival curves. In other words, endoscopically protruding type tumors with a longitudinal length of irradiation of 3.0 cm or less, and good responses not only to laser treatment but also to other combined modalities are favorable factors for achieving long-term survival in patients with tracheobronchial malignancies undergoing endoscopic Nd:YAG laser treatment. Endoscopic Nd:YAG laser surgery is considered to be a promising part of the multi-modality treatment for unresectable advanced primary and metastatic malignancies of the trachea.

Aged↗

Homeostatic recovery of interstitial cell populations in Hydra.

The growth of interstitial cell populations in Hydra magnipapillata was examined following transplantation of small numbers of interstitial cells into "epithelial animals" which lacked all cell types in the interstitial cell lineage. The distribution pattern of transplanted interstitial cells during the growth phase was examined by staining whole animals with toluidine blue and cell numbers were determined by maceration. The following results were obtained: (1) Transplanted interstitial cells formed a contiguous patch which spread distoproximally but not circumferentially. (2) The displacement of interstitial cells from parents to buds was a random process; buds incorporated interstitial cells only when they were formed in the vicinity of the patch. (3) Interstitial cells increased exponentially in number with a doubling time of 1.8 days for at least 10 days after transplantation, which is faster than the normal doubling time of 2.8 days. (4) The self-renewal probability at low interstitial cell levels was estimated to be 0.72, which was higher than the normal value of 0.64. This increase was attained by lowering the fraction of nematocyte differentiation. These results indicate that the homeostatic recovery of interstitial cell populations is attained by increasing the self-renewal probability rather than by preferential retention of interstitial cells in parent animals at the expense of buds (Heimfeld, 1985).

Animals↗