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Biomedical subjects

Daisuke Suzuki

Publications and source records attributed to Daisuke Suzuki.

At least 19 recordsLinked to original sources

A novel, noninvasive diagnostic probe for hydroa vacciniforme and related disorders: detection of latency-associated Epstein-Barr virus transcripts in the crusts.

OBJECTIVE: To establish a new diagnostic method for Epstein-Barr virus (EBV)-associated cutaneous disorders. DESIGN: Skin biopsy is usually required to confirm the latent EBV infections in cutaneous lesions of EBV-associated NK/T-cell lymphoproliferative disorders, including hydroa vacciniforme (HV) and hypersensitivity to mosquito bites (HMB). We have devised a novel, noninvasive method to detect EBV-encoded small RNA (EBER), BamHI A rightward transcripts (BARTs) in the skin crusts and scales of such patients. PATIENTS: Six patients with EBV-associated cutaneous lesions were enrolled in the present study, including three patients with HV, one with HV-like eruptions and chronic active EBV infection, and two with EBV-associated cutaneous lymphoma. MAIN OUTCOME MEASURES: RNA was extracted from the crusts obtained from the cutaneous lesions by forceps, converted to cDNA, and processed for polymerase chain reaction (PCR) amplification with a specific set of primers. The PCR products were assayed by a DNA sequencer. RESULTS: Intact RNAs were successfully extracted from the crusts as well as control materials. EBER1 and BARTs RNAs were detected in all 7 crusts, and in 6 of 7 crusts of EBV-associated cutaneous diseases, respectively. One of 23 crusts from non EBV-associated diseases was positive for EBER1 RNA. The sensitivity and specificity of our assay for latent EBV infection were 100% and 95.8% for EBER1 RNA, and 85.7% and 100% for BARTs mRNA, respectively. The correct DNA sequence for EBER1 and BARTs was confirmed in the PCR products by a direct sequencing method. CONCLUSIONS: Our procedure may be of use as a biomarker for EBV-associated cutaneous lesions, including HV, HMB, and NK/T-cell lymphomas.

Adolescent↗

Anatomical study of the femoral and tibial insertions of the anterolateral and posteromedial bundles of human posterior cruciate ligament.

For posterior cruciate ligament (PCL) reconstruction, two root, anterolateral and posteromedial bundles restruction are performed. However, little has been mentioned of anatomical measurements of the insertions to the bone of these bundles in previous publications. The aim of this study is to determine the precise anatomical measurements of the femoral and tibial insertions for anterolateral and posteromedial bundles of PCL. A total of 32 femur and 33 tibiae were selected from 50 cadavers after exclusion of knees that displayed macroscopically degenerative changes or evidence of trauma. PCL were divided into anterolateral bundles and posteromedial bundles to the insertion footprint, and those locations were measured and described. The distance from the center of the femoral insertions of the anterolateral and posteromedial bundles, and the Wrisberg ligament to the anterior margin of the medial femoral condyle averaged 9.6, 10.6, and 17.1 mm, respectively. The distance from the center of the femoral insertions of the anterolateral, posteromedial bundles, and Wrisberg ligament to the intercondylar roof averaged 4.8, 11.4, and 10.4 mm, respectively. The distance from the medial margin of the articular cartilage of the tibial plateau to the center of the tibial insertions of the anterolateral and posteromedial bundles averaged 51.0 and 50.0% of the total widest width of the tibial plateau, respectively. The vertical distance from the tibial insertion of the center of the posteromedial bundle to the plane of the tibial articular surface averaged 4.6 mm. This study leads to a better definition of the anatomy of the anterolateral and posteromedial bundles of PCL. It is very important to know the precise anatomy of PCL bundles when performing PCL reconstruction, and to evaluate PCL reconstruction surgery on an anatomical basis.

Cadaver↗

A case with membranous lupus nephritis developing after a twenty-year remission of membranoproliferative glomerulonephritis.

A 30-year-old woman who showed remission of membranoproliferative glomerulonephritis (MPGN) 20 years previously developed membranous lupus nephritis (MLN). She had photosensitivity, facial erythema, proteinuria of 2.59 g/24 hr, anti-nuclear antibody and anti-ds-DNA antibody. To confirm whether a misdiagnosis of MPGN was made 20 years ago, the clinical data at that time were evaluated retrospectively. She had only mild proteinuria and hematuria but no photosensitivity or facial erythema. Anti-nuclear antibody was negative. Renal biopsy showed occasional lobulation and glomerular capillary double contour. The diagnosis of MPGN was definite. This might be a rare case of one person suffering from two types of glomerulonephritis, MPGN and MLN.

Adult↗

Relationship between the expression of advanced glycation end-products (AGE) and the receptor for AGE (RAGE) mRNA in diabetic nephropathy.

OBJECTIVE: The receptor for advanced glycation end-products (RAGE) is one of several advanced glycation end-product (AGE)-specific cellular receptors. To evaluate the relationship between AGE and RAGE in renal tissues of diabetic nephropathy (DN), we examined the levels of expression of AGE protein and of RAGE mRNA. We also investigated the relationships among the degree of mesangial expansion and the expression of AGE and RAGE mRNA. PATIENTS AND METHODS: Renal biopsy tissues were obtained from 20 patients with DN. We performed immunohistochemical staining using monoclonal anti-AGE antibody and in situ hybridization using non-radioactive oligonucleotide RAGE probe on these tissues. We also examined five control renal samples. We evaluated the intensity of positive anti-AGE antibody staining and the percentage of cells positive for RAGE mRNA. We also measured the total glomerular area and mesangial area in glomeruli using an automatic image analyzer. We then calculated the percentage of mesangial area as a proportion of the total glomerular area (%Mes). RESULTS: Anti-AGE antibody was detected in the expanded mesangial matrix in DN but not in control samples. RAGE mRNA expression was detected mainly in glomerular intrinsic cells, including glomerular mesangial and epithelial cells, in both DN and control. %Mes correlated significantly with both the intensity of anti-AGE antibody positive staining and the percentage of cells positive for RAGE mRNA. CONCLUSIONS: Our findings suggest that both AGE and RAGE are associated with the development and progression of DN.

Adult↗

Hybrid microgels with reversibly changeable multiple brilliant color.

We report reversibly color changeable hybrid microgels that tune multiple brilliant colors due to interparticle interactions of SPR using several structured nanoparticles. The interparticle interactions were brought out using the thermosensitive swelling/deswelling property of microgel. We employ N-isopropylacrylamide (NIPAM) and glycidyl methacrylate (GMA) copolymerized microgels (NG microgels) as templates for in situ synthesis of Au nanoparticles. The seed Au nanoparticles could be stably grown by successive reduction of Au and Ag in the microgels. Interestingly, the hybrid microgels were able to exhibit multiple brilliant colors by attaching Au/Ag multiple core/shell bimetallic nanoparticles in the microgels, and the color change reversibility of each hybrid microgel was accomplished by adjusting the nanoparticles' sizes. Obtained microgels shown in this study will find important applications such as in biomedical and electronic devices.

Journal Article↗

Anatomical study of the femoral and tibial insertions of the anteromedial and posterolateral bundles of human anterior cruciate ligament.

BACKGROUND: Recently, anatomical anterior cruciate ligament reconstruction with 2-bundle reconstruction has been proposed. Few previous publications have mentioned anatomical measurements of the insertions of these bundles. PURPOSE: To determine the precise anatomical measurements of the femoral and tibial insertions for anteromedial and posterolateral bundles of anterior cruciate ligament grafts. STUDY DESIGN: Descriptive laboratory study. METHODS: Thirty-two femurs and 31 tibias were selected. The anterior cruciate ligament was divided into anteromedial and posterolateral bundles to the insertion footprint. Six measurements of the femoral insertion and 4 measurements of the tibial insertion were examined. Locations of the femoral insertions were examined using lateral radiographs of the femur. RESULTS: The distance between the center of the femoral insertions of the anteromedial and posterolateral bundles and the posterior margin of the lateral femoral condyle averaged 7.6 and 7.0 mm, respectively. The distance between the center of the femoral insertions of the anteromedial and posterolateral bundles to the intercondylar roof averaged 4.1 and 11.3 mm, respectively. The sagittal distance between the center of the tibial insertions of the anteromedial and posterolateral bundles from the anterior margin of the tibial articular cartilage averaged 13.0 and 14.7 mm, respectively. The distance from the lateral margin of the articular cartilage of the tibial plateau to the center of the tibial insertions of the anteromedial and posterolateral bundles averaged 44.2% and 52.4% of the total widest width of the tibial plateau, respectively. On the lateral radiograph of femoral condyles, the center of the anteromedial bundle was located at 31.9% from the posterior margin of the femoral condyle and 26.9% from the roof, and that of the posterolateral bundle was located at 39.8% from the posterior margin of the femoral condyle and 53.2% from the roof. CLINICAL RELEVANCE: It is important to know the precise anatomy of anterior cruciate ligament bundles when performing reconstruction and to evaluate anterior cruciate ligament reconstruction surgery on an anatomical basis.

Anterior Cruciate Ligament↗

Unique regulation of thyroid hormone metabolism during fasting in the house musk shrew (Suncus murinus, Insectivora: Soricidae).

The active hormone, 3,3',5-triiodothyronine (T3) is derived from thyroxine (T4) by the action of iodothyronine 5'-deiodinases (5'-D). By now two types of 5'-D have been identified; Type 1 (D1) and type 2 (D2). A relative contribution of these isotypes to the circulating T3 levels in the human remains to be determined whereas a number of reports indicate that, under physiological conditions, D1 plays a major role in maintaining circulating T3 levels in rodents. In both human and rodents, sickness and starvation reduce serum T3 concentration mainly through decrease in D1 activity. Recently, we found that the house musk shrew (Suncus murinus, Insectivora: Soricidae) has a different tissue distribution of D1 activity. Because compared to rodents D1 activity in the shrew was found only in liver at a much reduced level, D2 rather than D1 may play a role in the maintenance of serum T3. Therefore, we questioned how D1 and D2 activities change in fasted shrews and how these changes affect circulating thyroid hormone levels. We thus starved shrews for 24, 48 or 72 h and measured changes in serum concentration of T3, T4, and 3,3',5'-triiodothyronine (reverse T3, rT3) and D1 activities as well as its mRNA expression in liver. D2 activities were also measured in brown adipose tissue (BAT) and cerebral cortex of shrews. Unlike in human and rodents, T3 levels in shrews remained constant during fasting while T4 levels tended to decrease, resulting in an increase in its T3/T4 ratio. On the other hand, changes in rT3 levels were similar to those in human and rodents, being elevated with fasting. D1 mRNA and its activity were significantly reduced in the liver whereas D2 activities in BAT and cerebral cortex were increased by fasting. These results indicated that fasting in shrews also reduced hepatic D1 activity but it did not affect circulating T3 levels. The increased T3/T4 ratio together with increased D2 activity in BAT and cerebral cortex with fasting suggest that D2 rather than D1 is responsible for the maintenance of T3 levels in the house musk shrew.

Adipose Tissue, Brown↗

Pathogenic link between hydroa vacciniforme and Epstein-Barr virus-associated hematologic disorders.

OBJECTIVES: To determine the pathogenic association of latent Epstein-Barr virus (EBV) infections with both typical hydroa vacciniforme (HV) and severe HV-like eruptions, and to survey the complications and outcomes of patients. DESIGN: Case series. PATIENTS: Twenty-nine patients with HV or severe HV-like eruptions. INTERVENTIONS: In situ hybridization and immunostaining of biopsy specimens; extraction of DNA samples from cutaneous lesions and/or peripheral blood mononuclear cells for EBV DNA assay. MAIN OUTCOME MEASURES: Clinicopathologic manifestations, hematologic findings, complications, and outcomes; presence of latent EBV infection. RESULTS: T cells positive for EBV-encoded small nuclear RNA (EBER) were detected, to various degrees, in cutaneous infiltrates in 28 (97%) of 29 patients, including all 6 patients with definite HV with a positive phototest reaction, 11 of 12 patients with probable HV without evidence of photosensitivity, and all 11 patients with severe HV associated with systemic symptoms. In addition to EBER-positive T cells, many cytotoxic T lymphocytes expressing T-cell intracellular antigen 1 and granzyme B were present in the cutaneous lesions. Natural killer (NK) cells were absent or at a background level. The UV-induced cutaneous lesions showed histopathologic findings consistent with those of HV, containing many EBER-positive cells. Although no hematologic abnormalities were found in the definite and probable HV groups, the amounts of EBV DNA were increased in the peripheral blood mononuclear cells. By contrast, the severe HV group had markedly increased levels of EBV DNA associated with NK-cell lymphocytosis, and complications including chronic active EBV infection, hypersensitivity to mosquito bites, and hemophagocytic syndrome. Five patients with severe disease died of EBV-associated NK/T-cell lymphomas or hemophagocytic syndrome 2 to 14 years after onset. CONCLUSION: Both typical and severe HV are included within the spectrum of cutaneous disorders mediated by EBV-infected T cells, and the severe HV group may have overt EBV-associated NK/T-cell lymphoproliferative disorders with a frequently fatal outcome.

Adolescent↗

Paludibacter propionicigenes gen. nov., sp. nov., a novel strictly anaerobic, Gram-negative, propionate-producing bacterium isolated from plant residue in irrigated rice-field soil in Japan.

A strictly anaerobic, propionate-producing bacterial strain (WB4T) isolated from rice plant residue in anoxic rice-field soil in Japan was characterized phenotypically and phylogenetically. Cells were Gram-negative, non-motile, non-spore-forming, short rods. The strain utilized various sugars and produced propionate and acetate as major fermentation products with a small amount of succinate. The optimum growth temperature was 30 degrees C. Oxidase, catalase and nitrate-reducing activities were negative. The major cellular fatty acids were anteiso-C(15 : 0), C(15 : 0) and anteiso-C(17 : 0) 3-OH. Menaquinone MK-8(H4) was the major respiratory quinone. The genomic DNA G+C content was 39.3 mol%. Phylogenetic analysis based on the 16S rRNA gene sequence placed the strain in the phylum 'Bacteroidetes'. The closest relative to strain WB4T was an environmental clone from water contaminated with equine manure (sequence similarity of 99.7 %) and the strain formed a distinct cluster with other environmental clones mainly from freshwater sediments. The closest recognized species were members of the genus Dysgonomonas, with 16S rRNA gene sequence similarities of 90.9-89.8 %. Bacteroides merdae was the next closest recognized species (similarity of 88.7 % to the type strain). Given that the ecological, physiological and chemotaxonomic characteristics of strain WB4T were different from those of any related species, a new genus and species Paludibacter propionicigenes gen. nov., sp. nov., is proposed to accommodate it. The type strain is WB4T (= JCM 13257T = DSM 17365T).

Agriculture↗

Xylanibacter oryzae gen. nov., sp. nov., a novel strictly anaerobic, Gram-negative, xylanolytic bacterium isolated from rice-plant residue in flooded rice-field soil in Japan.

A strictly anaerobic, xylanolytic bacterium, strain KB3(T), isolated from rice-plant residue in flooded anoxic rice-field soil in Japan, was characterized phenotypically and phylogenetically. Cells were Gram-negative, non-motile, non-spore-forming, short to filamentous rods. Growth of the strain was remarkably stimulated by the addition of haemin to the medium. The novel strain utilized various sugars including xylan, xylose, pectin and carboxymethylcellulose and produced acetate, propionate and succinate with a small amount of malate. Propionate production was stimulated by the addition of a B-vitamin mixture or cobalamin to the medium. The novel strain was slightly acidophilic with an optimum pH 5.7-6.2 and the optimum growth temperature was 30 degrees C. Oxidase, catalase and nitrate-reducing activities were negative. Aesculin was hydrolysed. The major cellular fatty acids were anteiso-C(15 : 0) and iso-3-OH C(17 : 0). The major respiratory quinones were menaquinones MK-12(H(2)) and MK-13(H(2)). The genomic DNA G+C content was 43.6 mol%. Phylogenetic analysis based on 16S rRNA gene sequence placed the strain in the phylum Bacteroidetes. The closest related species was Prevotella bivia with a 16S rRNA gene sequence similarity of 89.5 %. Prevotella albensis and Prevotella oulorum were the next closest recognized species with sequence similarities of 89.1 %. Based on a comprehensive examination of the differences in phylogenetic, ecological, physiological and chemotaxonomic characteristics of strain KB3(T) and those of related species, a novel genus and species, Xylanibacter oryzae gen. nov., sp. nov., is proposed to accommodate strain KB3(T). The type strain of the novel species is KB3(T) (=JCM 13648(T)=DSM 17970(T)).

Bacteria, Anaerobic↗

Distal fibular length needed for ankle stability.

BACKGROUND: The fibula is commonly used for bone grafts. Previous clinical and biomechanical studies have suggested that the length of the residual portion of the distal part of the fibula has an important effect on the long-term stability of the ankle joint. However, we cannot find clear-cut guidelines for the amount of bone that can be harvested safely. METHODS: Using six normal fresh-frozen cadaver legs, motions of the tibia, talus and calcaneus were measured. The fibula was cut sequentially 3 cm from the proximal tip of the fibula and distally 10 cm, 6 cm, and 4 cm from the distal tip of the lateral malleolus. The angular motion of each bone was measured while a medial and lateral traction force of 19.6 N was applied to the proximal tibia. Angles of the tibia, talus, and calcaneus were measured. RESULTS: Sequential resection of the fibula increased the inversion angles of the ankle joint. The proximal 3-cm cut increased the inversion angle from 42.1 +/- 6.2 degrees to 49.6 +/- 3.6 degrees, and the distal 4-cm cut increased the angle from 57.6 +/- 6.6 degrees to 67.4 +/- 5.9 degrees. The rotational angles were almost constant with sequential resections of the fibula; however, the distal 4-cm cut increased the rotational angle from 11.3 +/- 25.1 degrees to 78.7 +/- 37.5 degrees. CONCLUSIONS: The whole fibula including the head is essential for the stability of the ankle joint complex, and the distal fibula is responsible for stabilizing the ankle mortise during external rotation and inversion. We recommend fixation of the syndesmosis or bracing to prevent ankle joint instability with rotation of the talus in the mortise, especially when the distal fibula is shortened 6 cm or more.

Aged↗

Accuracy and efficiency of left ventricular ejection fraction analysis, using multidetector row computed tomography: effect of image reconstruction window within cardiac phase, slice thickness, and interval of short-axis sections.

BACKGROUND: The aim of the present study was to assess the accuracy and efficiency of left ventricular ejection fraction (LVEF) analysis by multidetector row computed tomography (CT). METHODS AND RESULTS: The CT data of 21 patients were analyzed by semi-automated software on a workstation. In analysis of LVEF using systolic volumes in the 6 phases (30-55%), systolic images of 10% interval (35, 45, 55%) were underestimated with a mean measurement error of -0.4% and the standard error of the estimate (SEE) of 0.6%, compared with the LVEF using images of 5% interval. In analysis of LVEF using 3-slice thicknesses of axial images (1, 2, and 3 mm), and 3-slice numbers of short-axis sections (10 14, and 30 slices), there was no significant difference between the SEE of the intraobserver reproducibility and that of the analysis with 30 short-axis sections using axial images of 1-, 2- and 3-mm thickness, and that with 14 short-axis sections using axial images of 1- and 2-mm thickness. The mean analysis times were 96.9 s, 119.8 s, and 227.0 s for the analysis with 10, 14, and 30 short-axis sections, respectively. CONCLUSION: The proper selection of the reconstruction interval in the cardiac phase, the slice thickness of the axial images, and the number of short-axis sections reduces the analysis time, maintaining the accuracy of LVEF analysis. This will be acceptable for practical use at present, although more accurate analysis is preferable.

Adult↗

Construction of mouse 129/Ola BAC library for targeting experiments using E14 embryonic stem cells.

Gene targeting is a powerful method of specifically modifying genes of interest. It has been most consistently successful in the 129 mouse strain, because the embryonic stem (ES) cells of 129 mice are relatively easy to culture. In gene-targeting experiments, the use of ES cell-derived genomic clones as a source of homology arms is desirable, because the genetic variation among mouse strains results in a reduced frequency of homologous recombination. In this study, we generated an arrayed mouse 129/Ola BAC library derived from E14.1 ES cells, one of the frequently used ES cell lines. More than 135,000 BAC clones with a mean insert size of 110 kb were isolated. This library is estimated to represent a 5.5-fold mouse genome coverage. The BAC clones can be screened within 2 days by PCR. Considering that all 8 loci so far examined are contained in this BAC library, we believe it will be a useful resource for gene targeting studies using E14 ES cells as well as for genome analysis.

Animals↗

Change in Ucp1 mRNA expression following long-term cold exposure under normal or high-fat diet regimes in the cold-intolerant mammal, Suncus murinus.

The house musk shrew (Suncus murinus), or suncus, is a unique experimental mammal that is cold intolerant. However, even basic knowledge of brown adipose tissue (BAT), which is important for non-shivering thermogenesis (NST), is minimal. Therefore, we exposed suncus for 18 days to mild cold temperatures (8-14 degrees C) and/or a high-fat diet, which are factors that increase NST, and measured two mRNAs that are critical for NST in BAT, uncoupling protein 1 (Ucp1) and type II 5'-deiodinase (D2). Neither mild cold exposure nor a high-fat diet alone induced up-regulation of the mRNAs. However, combinations of cold exposure and high-fat diet significantly increased both mRNAs. Therefore, cold intolerance in suncus may be partly caused by dietary components.

Adaptation, Physiological↗

Cloning of putative uncoupling protein 1 cDNA in a cold-intolerant mammal, the house musk shrew (Suncus murinus).

The house musk shrew (Suncus murinus), or suncus, is a unique experimental animal. We recently showed that this mammal is cold intolerant and hypothesized that its sensitivity to cold is caused by low thermogenic activity in brown adipose tissue (BAT). Thermogenesis in BAT is performed by a unique mitochondrial protein, uncoupling protein 1 (UCP1). Interestingly, only eutherians possess UCP1, and some traits in the suncus resemble those in the Ucp1-ablated mouse, including cold intolerance, histology of BAT, and obesity resistance. In a previous study, we hypothesized that UCP1 may not be present in BAT of the suncus or may be dysfunctional. Therefore, we performed cDNA cloning of suncus Ucp1 and compared it to homologs from other species. The deduced amino acid sequence showed high similarity to other mammalian UCP1. Northern blot analysis revealed mRNA in BAT, as in other mammals. However, a difference in an amino acid residue was observed in an important residue for thermogenesis. Genomic sequence analysis showed that this difference existed in our two genetically distant laboratory colonies. These results suggest that cold intolerance in the suncus is derived from low thermogenic activity of UCP1 and may exist in wild house musk shrews.

Amino Acid Sequence↗

[Clinical significance of IgM deposition in the mesangium and mesangial hypercellularity in adult minimal change nephrotic syndrome].

Minimal change nephrotic syndrome(MCNS) typically shows no abnormalities in light microscopy. However, there are some minor light microscopic abnormalities that are considered to be MCNS variants. In pediatric nephrology, some researchers have reported that IgM deposition in the mesangium and mesangial hypercellularity are related to the response to steroid therapy and the long-term course. However, it is not clear whether IgM deposition in the mesangium and mesangial hypercellularity is responsible for the clinical course or the steroid response of patients with adult MCNS. To investigate the clinical importance of IgM deposition in the mesangium and mesangial hypercellularity, clinical records, follow up data, and renal samples of 47 patients with MCNS were reviewed. We also compared the histological data with those of a normal control group (n = 5). In our study, the presence of mesangial IgM deposition did not predict the patient's clinical course or responsiveness to steroid therapy. Increase in the number of nuclei in the glomeruli and PAS-positive area also did not correlate with the clinical course or responsiveness to steroid therapy. The data suggest that mesangial IgM deposits and increased mesangial cellularity in adult MCNS may not predict the clinical course or steroid response. However, we investigated only 47 samples in this study, therefore, further studies are necessary to identify the importance of IgM deposition in the mesangium and mesangial hypercellularity in adult MCNS.

Adult↗

[Case of rheumatoid arthritis with various histological lesions of the kidney].

We experienced a case of rheumatoid arthritis with nephrotic syndrome. A renal biopsy specimen from this patient showed various renal histological changes. The patient was a 50-year-old man who was diagnosed as having rheumatoid arthritis in 1987. We performed a renal biopsy because he had persistent proteinuria from March in 2002. The renal biopsy specimen showed amyloid AA and P protein deposition in the glomeruli. Moreover mild mesangial proliferation was recognized. IgA-deposition in the mesangial area, and granular-deposition of IgG along the glomerular capillary wall were also observed. In electron microscopy, electron dense deposits were recognized in the mesangial area and subepithelium of the glomerular basement membrane. From these findings, we diagnosed amyloid nephropathy, IgA nephritis and membranous nephropathy. Renal biopsy of patients with RA is useful not only for precise diagnosis, but also for selection of the appropriate treatment.

Amyloid Neuropathies↗