PubMed Health⌕ Search

Biomedical subjects

T Yasunaga

Publications and source records attributed to T Yasunaga.

At least 19 recordsLinked to original sources

Histomorphometric study on high-strength hydroxyapatite/poly(L-lactide) composite rods for internal fixation of bone fractures.

The purpose of this study was to investigate the bone-implant interface of high-strength hydroxyapatite (HA)/poly(L-lactide) (PLLA) composite rods. As reinforcing particles, two types of HA particles-calcined HA (c-HA) and uncalcined HA (u-HA)-were applied to allow comparison of their suitability as bioactive fillers. Four types of composites (c-HA30, c-HA40, u-HA30, and u-HA40), which contained 30 or 40% by weight of each HA particle, were used. Unfilled PLLA rods were used as controls. A hole was drilled in the distal femora of 50 rabbits, and a composite or unfilled PLLA rod was implanted in a press-fit manner. Two, 4, 8, and 25 weeks after implantation, the samples were examined histologically by light microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). An image analyzer was used for histomorphometric analysis of the bone-implant interface. An affinity index was calculated for each material; this was the length of bone directly apposed to the rods expressed as a percentage of the total length of the rod surface. In all the composites, histologic examination showed new bone formation at 2 weeks after implantation. The bone gradually grew along the composite surface. SEM showed direct bone contact with the composites without intervening fibrous tissue. During follow-up, the affinity indices of all the composite rods were significantly higher than those of the unfilled PLLA rods (p < 0.01; two-way ANOVA). The maximum affinity index (41%) was attained at 4 weeks in c-HA40 rods. In contrast, little bone contact was seen in unfilled PLLA rods. The only significant difference in affinity indices among the composites was that c-HA40 had a higher affinity index than u-HA40 (p < 0.05 at 4 weeks). No disintegration of rods or polymer debris, which could elicit inflammatory tissue reactions, was observed even at 25 weeks. Our results indicate that osteoconductive bone formation on composites could enhance the stability between bone and implant in fracture repair.

Absorbable Implants↗

V-Type H+-ATPase/synthase from a thermophilic eubacterium, Thermus thermophilus. Subunit structure and operon.

V-type ATPase (V(o)V(1)) capable of ATP-driven H(+) pumping and of H(+) gradient driven ATP synthesis was isolated from a thermophilic eubacterium, Thermus thermophilus. When the enzyme was analyzed by gel electrophoresis in the presence of sodium dodecyl sulfate, it showed eight polypeptide bands of which four were subunits of V(1). We also isolated the V(o)V(1) operon, containing nine genes in the order of atpG-I-L-E-X-F-A-B-D, which encoded proteins with molecular sizes of 13, 43, 10, 20, 35, 11, 64, 53, and 25 kDa, respectively. The last four genes were identified as those for V(1) subunits; atpA, B, D, and F encoded the A, B, gamma, and delta subunits, respectively. The first five genes, atpG-atpX, were identified as genes for the V(o) subunits. The product of atpL, the proteolipid subunit, lacked a 19-amino acid presequence and, unlike V-type ATPases, contained two membrane-spanning domains rather than four. The hydrophobic 43-kDa product of atpI is the smallest member so far found of the eukaryotic 100-kDa subunit family. Its electrophoretic band overlapped with the band of the A subunit. Therefore, all the gene products were found in our purified V(o)V(1). We isolated the A(3)B(3) subcomplex reconstituted from the isolated subunits and the A(3)B(3)gamma subcomplex from subunit-expressing Escherichia coli. Electron microscopic observation of these subcomplexes revealed that the gamma subunit of V(1) filled the central cavity of A(3)B(3) and might be central subunit, similar to the gamma subunit of F(1)-ATPase.

Amino Acid Sequence↗

Structural basis for the higher Ca(2+)-activation of the regulated actin-activated myosin ATPase observed with Dictyostelium/Tetrahymena actin chimeras.

Replacement of residues 228-230 or 228-232 of subdomain 4 in Dictyostelium actin with the corresponding Tetrahymena sequence (QTA to KAY replacement: half chimera-1; QTAAS to KAYKE replacement: full chimera) leads to a higher Ca(2+)-activation of the regulated acto-myosin subfragment-1 ATPase activity. The ratio of ATPase activation in the presence of tropomyosin-troponin and Ca(2+) to that without tropomyosin-troponin becomes about four times as large as the ratio for the wild-type actin. To understand the structural basis of this higher Ca(2+)-activation, we have determined the crystal structures of the 1:1 complex of Dictyostelium mutant actins (half chimera-1 and full chimera) with gelsolin segment-1 to 2.0 A and 2.4 A resolution, respectively, together with the structure of wild-type actin as a control. Although there were local changes on the surface of the subdomain 4 and the phenolic side-chain of Tyr230 displaced the side-chain of Leu236 from a non-polar pocket to a more solvent-accessible position, the structures of the actin chimeras showed that the mutations in the 228-232 region did not introduce large changes in the overall actin structure. This suggests that residues near position 230 formed part of the tropomyosin binding site on actin in actively contracting muscle. The higher Ca(2+)-activation observed with A230Y-containing mutants can be understood in terms of a three-state model for thin filament regulation in which, in the presence of both Ca(2+) and myosin heads, the local changes of actin generated by the mutation (especially its phenolic side-chain) facilitate the transition of thin filaments from a "closed" state to an "open" state. Between 394 and 469 water molecules were identified in the different structures and it was found that actin recognizes hydrated forms of the adenine base and the Ca ion in the nucleotide binding site.

Actins↗

Acetylation at the N-terminus of actin strengthens weak interaction between actin and myosin.

The N-terminus of all actins so far studied is acetylated. Although the pathways of acetylation have been well studied, its functional importance has been unclear. A negative charge cluster in the actin N-terminal region is shown to be important for the function of actomyosin. Acetylation at the N-terminus removes a positive charge and increases the amount of net negative charges in the N-terminal region. This may augment the role of the negative charge cluster. To examine this possibility, actin with a nonacetylated N-terminus (nonacetylated actin) was produced. The nonacetylated actin polymerized and depolymerized normally. In actin-activated heavy meromyosin ATPase assays, the nonacetylated actin showed higher K(app) without significantly changing V(max), compared with those of wild-type actin. This is in contrast to the effect of the N-terminal negative charge cluster, which increases V(max) without changing K(app). These results indicate that the acetylation at the N-terminus of actin strengthens weak actomyosin interaction.

Acetylation↗

Biodegradation behavior of ultra-high-strength hydroxyapatite/poly (L-lactide) composite rods for internal fixation of bone fractures.

The purpose of this study was to investigate the biodegradation behavior of the ultra-high-strength hydroxyapatite/poly(L-lactide) (HA/PLLA) composite rods for fracture repair. Two kinds of composite materials were used in this study: u-HA/PLLA. which contained 30% by weight of uncalcined HA as reinforcing particles, and c-HA/PLLA, which contained 30% by weight of calcined HA as reinforcing particles. These composite rods were implanted in the subcutis and in the medullary cavities of rabbits. The specimens were removed at specific intervals between 2 and 52 weeks and the mechanical strength was measured for the rods in the subcutis, and the molecular weight and crystallinity were measured for the rods in both the subcutis and medullary cavities. The rod surfaces were examined using a scanning electron microscope (SEM). The specimens were examined histologically by light microscopy. The bending strength of the composites implanted in the subcutis was maintained at more than 200 M Pa at 25 weeks and at 150 MPa at 52 weeks. The molecular weight dropped to 45% of the initial values at 8 weeks and to approximately 10% at 52 weeks. Significant differences in the molecular weight were seen between c-HA/PLLA and u-HA/PLLA, with u-HA/PLLA showing a faster rate of decrease than c-HA/PLLA after 8 weeks. SEM demonstrated that HA particles disappeared increasingly from the rod surfaces over time and that the spaces left by these HA particles formed many pores in the composite surfaces at 52 weeks. Histologically, a fibrous tissue layer was formed around the composite rod from 4 weeks in the subcutis and in the diaphyseal area of the medullary canal. This became more mature over time. Bony tissue contact to the composites without fibrous tissue layers was seen in the metaphyseal area of the medullary canal. During the experimental period, there were no inflammatory cells such as mono- or multi-nuclear phagocytes. Although further long-term studies for degradation are needed, the composites have promising mechanical strength and no adverse tissue reaction for use as fracture-fixation devices during the experimental periods.

Animals↗

Chromosome of the enterohemorrhagic Escherichia coli O157:H7; comparative analysis with K-12 MG1655 revealed the acquisition of a large amount of foreign DNAs.

A complete Xba I and Bln I cleavage map was constructed for the chromosome of an enterohemorrhagic Escherichia coli (EHEC) O157:H7 strain isolated from an outbreak in Sakai City, Japan, in 1996. A comparative chromosome analysis with E. coli K-12 strain MG1655 was made. The EHEC chromosome was approximately 5600 kb in length, 1 Mb larger than that of MG1655. Despite the marked difference in chromosome length, the location and direction of seven rRNA operons of the EHEC strain were similar to those for MG1655. Overall organization of genes common in both strains is also highly conserved. Chromosome expansion was observed throughout the EHEC chromosome, albeit in an uneven manner. A large portion of the chromosome enlargement was observed in the region surrounding the replication terminus, particularly in a segment containing the terA locus. Sample sequencing of 3627 random shotgun clones suggested the presence of approximately 1550 kb strain-specific DNAs on the EHEC chromosome, most of which are likely to be of foreign origin.

Bacterial Toxins↗

Bonding behavior of ultrahigh strength unsintered hydroxyapatite particles/poly(L-lactide) composites to surface of tibial cortex in rabbits.

Unsintered hydroxyapatite particles/poly(L-lactide) (u-HA/PLLA) composites with an initial bending strength of up to 270 MPa were developed based on the hypothesis that inclusion of u-HA particles in a PLLA matrix might enhance bone bonding. The purpose of this study was to examine the bonding strength and behavior of these u-HA/PLLA composites on the surface of the bone cortex. Composites containing 30 (u-HA30), 40 (u-HA40), or 50 wt % (u-HA50) of fine u-HA particles (3-microm average particle size) were prepared. Semicolumnar plates of these composites and control PLLA plates were fixed with metal screws to the surface of both proximal tibial cortices in 45 rabbits. The loads required to detach the plates from the bone cortex surface, defined as the bonding strengths, were measured at 4, 8, and 25 weeks after implantation. Bonding strengths in the u-HA30 group at 8 weeks and in the u-HA40 and u-HA50 groups at each postimplantation time were significantly greater than in the PLLA group (post hoc test using Fisher's protected least significant difference method). At each postimplantation time histological examinations revealed direct contact between the bone and the u-HA/PLLA composite plates without any intervening fibrous tissue. There was no evidence of any inflammatory or foreign-body response in any group throughout the follow-up periods. The results of this study suggest that the biodegradable PLLA fixation plates amended with u-HA particles could be functionally superior to PLLA plates without particles.

Animals↗

Genomic analysis of male germ cell-specific actin capping protein alpha.

The Gsg3 gene which expresses specifically in haploid germ cells is a mouse testicular homolog of somatic cell type actin capping protein alpha (ACP alpha). We have obtained a mouse Gsg3 genomic clone using cDNA as a probe. Sequencing data showed that the Gsg3 gene was not interrupted by introns. The transcription initiation site of the gene was preceded not by a TATA box or GC rich promoter motifs, but by two consensus cAMP-response element (CRE) motifs at the putative position. Southern blotting analysis showed that Gsg3 is a single copy gene in the mouse, and conserved in mammals. Phylogenetic analysis showed that Gsg3 is a novel ACP alpha specific for haploid germ cells.

Amino Acid Sequence↗

Diagnostic problems of evaluating vertebral metastasis from breast carcinoma with a higher degree of malignancy.

BACKGROUND: Bone metastases from breast carcinoma are frequently observed as postoperative pathologic conditions; however, in many cases, diagnosis and treatment are difficult. Although most diagnoses of bone metastases are made by plain radiography (X-P) or bone scintigraphy, the use of magnetic resonance imaging (MRI) has enabled detailed imaging of foci, and many more lesions have become detectable. In the current study, the authors evaluated the relation between the diagnosis of bone metastases of breast carcinoma and clinicopathologic factors, especially those of proliferative activity and effects of treatment. METHODS: The subjects consisted of 51 breast carcinoma patients (mean age, 51.2 years) with vertebral metastases diagnosed by plain radiography, bone scintigraphy, or MRI. Twenty-eight of the 51 patients were premenopausal and 27 of the 51 had bone metastases only. The patients were classified into the following groups: Group A, 24 patients who showed similar findings in plain radiography, bone scintigraphy, and MRI; Group C, 14 who showed no abnormalities on radiography or bone scintigraphy but whose lesions were diagnosed by MRI only; and Group B, 13 patients with findings intermediate between Groups A and C. The proliferative activity of tumors was evaluated by determining the level of DNA polymerase alpha. RESULTS: Regarding the relation to clinicopathologic factors, a significant number of patients with estrogen receptor (ER) negative tumors who had a high level of DNA polymerase alpha, short disease free intervals (DFI), and metastases to other organs were included in Group C. Prognoses of patients in Group C were poor. CONCLUSIONS: For the diagnosis of breast carcinoma with bone metastasis, different correlations were noted among the various biologic characteristics, such as ER status and proliferative activity. That is, bone scintigraphy sufficiently reflected foci in patients with ER positive tumors or tumors with low proliferation, whereas bone scintigraphy was false-negative in patients with ER negative or highly proliferative tumors, showing that MRI was useful in diagnosing such patients. Therefore, consideration of malignant features, such as proliferative activity and ER status, is believed necessary during the postoperative follow-up of breast carcinoma patients.

Adult↗

When and how to combine growth hormone with a luteinizing hormone-releasing hormone analogue.

The effect of combined treatment with growth hormone (GH) and a luteinizing hormone-releasing hormone (LHRH) analogue, or GH alone, on pubertal height gain was assessed in an uncontrolled study in 15 boys and 10 girls with GH deficiency (GHD). Seven boys and six girls were treated with GH alone (group 1), and eight boys and four girls were treated with a combination of GH and an LHRH analogue during puberty (group 2). Mean ages (+/- SD) at the start of GH treatment and at the onset of puberty were significantly lower in group 2 (8.0 +/- 3.3 years and 11.2 +/- 0.8 years, respectively, in boys, and 6.3 +/- 1.6 years and 10.8 +/- 0.7 years in girls) than in group 1 (12.8 +/- 1.9 years and 13.7 +/- 1.4 years in boys, and 11.2 +/- 1.0 years and 12.5 +/- 1.2 years in girls). Height at the onset of puberty was less in group 2 than in group 1, but the difference was significant only for the boys. Combination treatment was started at a mean age of 11.7 +/- 1.2 years in boys and 11.5 +/- 1.0 years in girls. The duration of the combination treatment was 5.1 +/- 1.5 years in boys and 2.3 +/- 0.7 years in girls. The duration of the period between the onset of puberty and the end of GH treatment was significantly longer in group 2 (6.8 +/- 1.2 years in boys and 5.5 +/- 1.0 years in girls) than in group 1 (4.3 +/- 1.6 years in boys and 3.6 +/- 1.4 years in girls). The pubertal height gain was also significantly greater in group 2 (36.7 +/- 6.5 cm in boys and 29.0 +/- 8.3 cm in girls) than in group 1 (21.9 +/- 4.1 cm in boys and 18.6 +/- 4.1 cm in girls). Final height was significantly greater in group 2 than in group 1 in boys. Although there was no significant difference in final height between groups in the girls, the change in height SDS from the start of GH treatment until final height was significantly greater in group 2 (2.7 +/- 1.6 in boys and 4.5 +/- 0.5 SD in girls) than in group 1 (1.0 +/- 0.8 in boys and 1.8 +/- 0.9 SD in girls), in both boys and girls. In conclusion, it appears that combination of an LHRH analogue and GH may increase the pubertal height gain and the final height of children with GHD. The improvement is attributed to the prolongation of the treatment period, permitting slow bone maturation, and to the maintenance of height velocity. This combination treatment appears to be more effective in boys than girls. To fully assess this therapeutic approach, prospective controlled studies are needed.

Adolescent↗

Complete nucleotide sequence of the prophage VT2-Sakai carrying the verotoxin 2 genes of the enterohemorrhagic Escherichia coli O157:H7 derived from the Sakai outbreak.

The enterohemorrhagic Escherichia coli (EHEC) O157:H7 strain RIMD 0509952, derived from an outbreak in Sakai city, Japan, in 1996, produces two kinds of verotoxins, VT1 and VT2, encoded by the stx1 and stx2 genes. In the EHEC strains, as well as in other VT-producing E. coli strains, the toxins are encoded by lysogenic bacteriophages. The EHEC O157:H7 strain RIMD 0509952 did not produce plaque-forming phage particles upon inducing treatments. We have determined the complete nucleotide sequence of a prophage, VT2-Sakai, carrying the stx2A and stx2B genes on the chromosome, and presumed the putative functions of the encoded proteins and the cis-acting DNA elements based on sequence homology data. To our surprise, the sequences in the regions of VT2-Sakai corresponding to the early gene regulators and replication proteins, and the DNA sequences recognized by the regulators share very limited homology to those of the VT2-encoding 933W phage carried by the EHEC O157:H7 strain EDL933 reported by Plunkett et al. (J. Bacteriol., p1767-1778, 181, 1999), although the sequences corresponding to the structural components are almost identical. These data suggest that these two phages were derived from a common ancestral phage and that either or both of them underwent multiple genetic rearrangements. An IS629 insertion was found downstream of the stx2B gene and upstream of the lysis gene S, and this might be responsible for the absence of plaque-forming activity in the lysate obtained after inducing treatments.

Bacterial Toxins↗

Adsorption/Desorption Kinetics of MoO2-4 onto gamma-Al2O3 by the Pressure-Jump Technique.

The kinetics and mechanisms of molybdate adsorption/desorption at the gamma-Al2O3/water interface were studied by using the pressure-jump apparatus with conductivity detection at 298 K. A double relaxation was observed due to the adsorption/desorption process. Adsorption data and triple-layer model (TLM) simulation results suggest the formation of both mono- and bidentate inner-sphere complexes (SMoO-4 and S2MoO4) at the gamma-Al2O3 surface. The intrinsic equilibrium constants (Kinteq) of the complexes were 10(6.5) M-2 and 10(16) M-4, respectively. Based on the relaxation theory and combined results of TLM simulation, a two-step process is proposed. The first step (k1, k-1) is the formation of an ion-pair complex through the electrostatic attraction between the reacting surface sites and MoO2-4 and H+. The second step (k2, k-2) involves a ligand exchange process, whereby one water molecule is replaced by one adsorbed MoO2-4 from the surface. The values of adsorption and desorption rate constants in the MoO2-4/gamma-Al2O3 system were determined to be kint1 = 5.23 x 10(6) M-2 s-1, kint-1 = 2.41 x 10 s-1, kint-2 = 1.74 s-1, and kint-2 = 3.26 x 10(-1) s-1. The intrinsic equilibrium constant from kinetic measurements (Kintkin) was 10(6) M-2, which was similar to the intrinsic equilibrium constant (Kinteq), 10(6.5) M-2, from the equilibrium studies. Copyright 1998 Academic Press.

Journal Article↗

Swing of the lever arm of a myosin motor at the isomerization and phosphate-release steps.

In muscle, the myosin head ('crossbridge') performs the 'working stroke', in which ATP is hydrolysed to generate the sliding of actin and myosin filaments. The myosin head consists of a globular motor domain and a long lever-arm domain. The 'lever-arm hypothesis' predicts that during the working stroke, the lever-arm domain tilts against the motor domain, which is bound to actin in a fixed orientation. To detect this working stroke in operation, we constructed fusion proteins by connecting Aequorea victoria green fluorescent protein and blue fluorescent protein to the amino and carboxyl termini of the motor domain of myosin II of Dictyostelium discoideum, a soil amoeba, and measured the fluorescence resonance energy transfer between the two fluorescent proteins. We show here that the carboxy-terminal fluorophore swings at the isomerization step of the ATP hydrolysis cycle, and then swings back at the subsequent step in which inorganic phosphate is released, thereby mimicking the swing of the lever arm. The swing at the phosphate-release step may correspond to the working stroke, and the swing at the isomerization step to the recovery stroke.

Adenosine Triphosphate↗

Synthesis and pharmacological characterization of novel 6-fluorochroman derivatives as potential 5-HT1A receptor antagonists.

A series of novel 6-fluorochroman derivatives was prepared and evaluated as antagonists for the 5-HT1A receptor. N-2-[[(6-Fluorochroman-8-yl)oxy]ethyl]-4-(4-methoxyphenyl)butylami ne (3; J. Med. Chem. 1997, 40, 1252-1257) was chosen as a lead, and structural modifications were done on the aliphatic portion of the chroman ring, the tether linking the middle amine and the terminal aromatic ring, the aromatic ring, and lastly the amine. Radioligand binding assays proved that the majority of the novel compounds behaved as good to excellent ligands at the 5-HT1A receptor, some of which were selective with respect to alpha1-adrenergic and D2-dopaminergic receptors. The antagonist activity of the compounds was assessed in the forskolin-stimulated adenylate cyclase assays in CHO cells expressing the human 5-HT1A receptors. Among the modifications attempted, introduction of an oxo or an optically active hydroxy moiety at the chroman C-4 position was effective in ameliorating the receptor selectivity. Six analogues were selected through the in vitro screens and further evaluated for their in vivo activities. A 4-oxochroman derivative (31n), having a terminal 1, 3-benzodioxole ring, demonstrated antagonist activities toward 8-OH-DPAT-induced behavioral and electrophysiological responses in rats.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Complete nucleotide sequences of 93-kb and 3.3-kb plasmids of an enterohemorrhagic Escherichia coli O157:H7 derived from Sakai outbreak.

Enterohemorrhagic Escherichia coli (EHEC) O157:H7, derived from an outbreak in Sakai city, Japan in 1996, possesses two kinds of plasmids: a 93-kb plasmid termed pO157, found in clinical EHEC isolates world-wide and a 3.3-kb plasmid termed pOSAK1, prevalent in EHEC strains isolated in Japan. Complete nucleotide sequences of both plasmids have been determined, and the putative functions of the encoded proteins and the cis-acting DNA sequences have been analyzed. pO157 shares strikingly similar genes and DNA sequences with F-factor and the transmissible drug-resistant plasmid R100 for DNA replication, copy number control, plasmid segregation, conjugative functions and stable maintenance in the host, although it is defective in DNA transfer by conjugation due to the truncation and deletion of the required genes and DNA sequences. In addition, it encodes several proteins implicated in EHEC pathogenicity such as an EHEC hemolysin (HlyA), a catalase-peroxidase (KatP), a serine protease (EspP) and type II secretion system. pOSAK1 possesses a ColE1-like replication system, and the DNA sequence is extremely similar to that of a drug-resistant plasmid, NTP16, derived from Salmonella typhimurium except that it lacks drug resistance transposons.

DNA, Bacterial↗

A novel frameshift mutation 840delA and a novel polymorphism D203A in the steroidogenic acute regulatory protein gene in a Japanese patient with congenital lipoid adrenal hyperplasia. Mutations in brief no. 117. Online.

Congenital lipoid adrenal hyperplasia (CLAH) is an autosomalrecessive disorder characterized by impaired production of all steroids including glucocorticoids, mineralocorticoids and sexsteriods. It has recently been reported that mutations in the steriodogenic acute regulatory protein (StAR) gene cause CLAH. We analyzed the StAR gene in a Japanese patient with CLAH. The patient was revealed to be a compound heterozygote bearing a nonsense mutation Q258X, changing codon 258 (CAG) encoding Gln to the stop codon TAG, and a novel framshift mutation 840delA resulting from deletion of one of the three adenosines normally present in codon 238 (AAA), thus leading to a frameshift after codon 237 (Thr) in the StAR gene. The patient was also revealed to be homozygous for a novel missense point mutation D203A, changing codon 203 (GAC) encoding Asp to GCC encoding Ala in the StAR gene. To elucidate the significance of the D203A mutation, we analyzed the StAR gene sequence in twenty normal subjects, and found that all of them were homozygous for the D203A mutation, indicating that the D203A mutation is an innocent polymorphism. In conclusion, we have identified a novel frameshift mutation 840delA which seems to cause 840delA and the first polymorphism D203A in the human StAR gene.

Adrenal Hyperplasia, Congenital↗

Bilateral fistulas from the internal mammary arteries and the bronchial arteries to the pulmonary arteries--a case report.

A 78-year-old man was admitted to hospital with heart failure and chronic bronchitis. A computed tomographic scan of the chest incidentally demonstrated bilateral abnormal vessels near the left atrium. Selective angiography showed that both internal mammary arteries and bronchial arteries communicated with the pulmonary arteries bilaterally. The patient refused surgery and was discharged on medical therapy. This is the first reported case of bilateral fistulas between the internal mammary arteries and bronchial arteries and the pulmonary arteries.

Aged↗