Biomedical subjects

Fumitake Gejyo

Publications and source records attributed to Fumitake Gejyo.

At least 145 records · Page 8Linked to original sources

PubMed2003

Role of osteoclastic dysfunction in the development of renal bone disease.

A 47-year-old-man was referred for treatment for end-stage renal failure. He had been diagnosed with type II adult onset osteopetrosis before the deterioration of his renal function. He presented with anaemia, severe hypocalcaemia, secondary hyperparathyroidism and azotaemia. An iliac bone biopsy revealed increased bone volume, disturbed osteoid calcification, active osteoclastic bone resorption and fibrous transformation in the bone marrow space. Incomplete osteoclastic dysfunction strongly suggested hypocalcaemia and secondary hyperparathyroidism, and the osteoclastic bone resorption also indicated secondary hyperparathyroidism, even though bone resorption was potentially suppressed. The present case shows that evidence of the involvement of osteoclastic dysfunction in the development of renal bone disease can be found in bone histology.

Humans↗

PubMed2003

LCAT-dependent conversion of prebeta1-HDL into alpha-migrating HDL is severely delayed in hemodialysis patients.

Prebeta1-HDL is a minor HDL subfraction that acts as an efficient initial acceptor of cell-derived free cholesterol. During 37 degrees C incubation, plasma prebeta1-HDL decreases over time due to its conversion to alpha-migrating HDL by lecithin:cholesterol acyltransferase (LCAT). This conversion may be delayed in hemodialysis patients who have decreased LCAT activity. To clarify whether LCAT-dependent conversion of prebeta1-HDL to alpha-migrating HDL is delayed in hemodialysis patients, prebeta1-HDL concentrations were determined in 45 hemodialysis patients and 45 gender-matched control subjects before and after 37 degrees C incubation with and without the LCAT inhibitor. It was found that the baseline prebeta1-HDL concentration in hemodialysis patients was more than twice that in the controls (44.9 +/- 21.4 versus 19.8 +/- 6.7 mg/L apoAI; P < 0.001). After 2-h incubation, the LCAT-dependent decrease in prebeta1-HDL in hemodialysis patients was about one-third of that in the controls (30 +/- 27 versus 97 +/- 17% of baseline; P < 0.01). The LCAT-dependent rate of decrease in prebeta1-HDL levels (DR(prebeta1)) was the same for samples from hemodialysis patients exhibiting normal (> or =1.03 mmol/L) and low HDL-cholesterol levels (32 +/- 32 versus 28 +/- 23% of baseline; NS). DR(prebeta1) was positively correlated with LCAT activity (r = 0.617; P < 0.001). In conclusion, the LCAT-dependent conversion of prebeta1-HDL to alpha-migrating HDL is severely delayed in hemodialysis patients. The impaired catabolism of prebeta1-HDL may accelerate atherosclerosis in hemodialysis patients.

Adult↗

PubMed2003

Role of megalin in endocytosis of advanced glycation end products: implications for a novel protein binding to both megalin and advanced glycation end products.

Advanced glycation end products (AGE) are filtered by glomeruli and reabsorbed and metabolized by proximal tubule cells (PTC). In renal failure, decreased renal AGE metabolism likely accounts for the accumulation in serum that is related to uremic complications. In diabetes, AGE generation is increased, and the handling mechanisms in PTC are likely associated with the pathogenesis of tubulointerstitial injury. It is therefore important to clarify the mechanisms of the AGE metabolism to develop a strategy for removing AGE in uremia and to elucidate the pathogenesis of diabetic nephropathy. To this end, this study focused on the molecular analysis of megalin, a multi-ligand endocytic receptor, in PTC. AGE uptake analysis was performed using the rat yolk sac-derived L2 cell line system established for the analysis of megalin's endocytic functions. The cells mediated specific internalization and degradation of AGE, which were significantly blocked by anti-megalin IgG, indicating that megalin is involved in the cellular processes. However, cell surface AGE-binding assays and ligand blot analysis revealed no evidence that megalin is a direct AGE receptor. Affinity chromatography and ligand blot analysis originally revealed that 200-kD and 400-kD proteins in the cells bind to AGE and the 200-kD protein to megalin in a Ca(2+)-dependent manner. The binding of megalin with the 200-kD protein was suppressed by receptor-associated protein (RAP), a ligand for megalin. In conclusion, megalin functions for endocytosis of AGE via an indirect mechanism. L2 cells express novel AGE-binding proteins, one of which may interact with megalin.

Animals↗

PubMed2003

Bioengineered implantation of megalin-expressing cells: a potential intracorporeal therapeutic model for uremic toxin protein clearance in renal failure.

Patients who have renal failure and are on dialysis therapy experience serious complications caused by low-molecular-weight uremic toxin proteins normally filtered by glomeruli and metabolized by proximal tubule cells (PTC). Dialysis-related amyloidosis is one such complication induced by systemic deposition of amyloid proteins derived from 12-kD beta(2)-microglobulin (beta(2)-m). Despite the use of high-flux membrane hemodialysis devices and direct absorbent columns, the removal of beta(2)-m is suboptimal, because the effects are transient and insufficient. Megalin is expressed in the apical membranes of PTC and recognized as a multiligand endocytic receptor that binds numerous low-molecular-weight proteins, including beta(2)-m. This study tested the feasibility of an intracorporeal therapeutic model of continuous beta(2)-m removal using megalin-expressing cell implantation. By cell association and degradation assays, rat yolk sac-derived L2 cells were identified to internalize and degrade beta(2)-m via megalin. The cells were effectively implanted within the subcutaneous tissues of nude mice using a type I collagen scaffold and a method inducing local angiogenesis. After nephrectomy and intraperitoneal injection with (125)I-beta(2)-m, it was found that the implanted cells took up the labeled ligand, efficiently removing it from the blood. Bioengineered implantation of megalin-expressing cells may represent a new supportive therapy for dialysis patients to compensate for the loss of renal protein metabolism and remove uremic toxin proteins.

Animals↗

PubMed2003

Genetic polymorphism of NPHS1 modifies the clinical manifestations of Ig A nephropathy.

Nephrin, the molecule responsible for congenital nephrotic syndrome of Finnish type, is crucial in maintaining the glomerular filtration barrier. Recently, its complete gene structure and common gene polymorphisms in its exons have been reported, although the functional and clinical significance of these polymorphisms has not yet been elucidated. We investigated a possible association of the NPHS1 polymorphisms with the development of Ig A nephropathy (IgAN), as well as the clinical and histologic manifestations in IgAN. A total of 464 Japanese subjects, including 267 patients with histologically proven IgAN and 197 healthy controls with normal urinalysis, were genotyped for the NPHS1 G349A, G2289A, and T3315C polymorphisms. The frequencies of the genotypes, alleles, and estimated haplotypes of NPHS1 polymorphisms were no different between patients with IgAN and the controls. Within the IgAN group, patients carrying at least one G allele of G349A tended to present with more proteinuria, lower renal function, and more severe histopathologic injury than those with the AA genotype, although the time from the first urinary abnormality to the renal biopsy was no different between both groups. The logistic regression analysis indicated that even after adjusting for the effect of proteinuria and hypertension the GG genotype of NPHS1 G349A was an independent risk factor for the deteriorated renal function at the time of diagnosis. This study suggests that the NPHS1 G349A polymorphism may be associated with heavy proteinuria and a decline in renal function in patients with IgAN.

Adolescent↗

PubMed2003

[Clinical evaluation of performance of a new diagnostic method for deep mycosis by measuring beta-glucan concentration in the blood].

beta-Glucan Test MARUHA for high sensitive diagnosis of deep mycosis which was developed recently detects (1-->3)-beta-D-glucan, a component of the cell wall. The performance of beta-Glucan Test MARUHA is evaluated in this report. Although existing methods to detect (1-->3)-beta-D-glucan have trouble with sulfa drugs, hemolysis, and immunoglobulin G (IgG), these problems were overcome by the beta-Glucan Test MARUHA: No effect was observed for beta-Glucan Test MARUHA at lower than 200 micrograms/ml, 500 mg/dl, and 6,000 mg/dl of sulfa drugs, hemoglobin, and IgG, respectively. The effect of drugs administrated on the measurement value of beta-glucan Test MARUHA was checked at several concentrations. However, almost no effect of drugs, such as, 5 kinds of antifungals, 8 kinds of antibiotics, a kind of antibacterial, 2 kinds of infusions, and a kind of contrast media was observed at the practical concentrations.

Biomarkers↗

PubMed2003

[Comparison of four diagnostic methods using clinical blood by measuring (1-->3)-beta-D-glucan].

Using Amebocyte lysate of horseshoe crab to measure (1-->3)-beta-D-glucan specifically, a component of the cell wall, several kinds of diagnostic methods for deep mycosis are in practical use in Japan. However, the most important problem is that the judgment of positive or negative is method dependent. To elucidate the cause of the problem, each measurement value of the identical sample by four methods, beta-Glucan Test Maruha (MARUHA), beta-Glucan Test Wako (WAKO). FUNGITEC G Test (FUNGITEC-G) and FUNGITEC G Test MK (FUNGITEC-MK) was compared with the clinical data using 119 cases and 289 tests. Each case was divided into three groups; proven fungal infection, probable fungal infection and non-fungal infection. The negative cases for all the methods tested in the groups of proven fungal infection and probable fungal infection were allergic bronchopulmonary aspergillosis and cryptococcosis, and that for all the methods tested except FUNGITEC-MK method in the group was pulmonary aspergilloma. It seems that these cases cannot be detected correctly by only measuring (1-->3)-beta-D-glucan. On the other hand, the ratio of false positive, positive for non-fungal infection group was high in the case of FUNGITEC-MK. About 23% against the total case was positive for FUNGITEC-MK method, but negative for MARUHA, WAKO, and FUNGITEC-G methods. Although the difference of the sensitivity among four methods was not observed, the specificity, the diagnostic efficiency, and the positive predictive value of FUNGITEC-MK method were remarkably lower than those of the other methods due to false positive measurement. In conclusion, MARUHA, WAKO and FUNGITEC-G except FUNGITEC-MK is not method dependent. It is suggested that FUNGITEC-MK detects non-specific reaction resulted in false positive.

Glucans↗

PubMed2003

Microfocus computed tomography analysis of early changes in bone microstructure in rats with chronic renal failure.

BACKGROUND/AIMS: Little is known about the microstructural changes in bone tissue in the early phase of chronic renal failure (CRF). In this study, we analyzed the bone tissue in a rat model of early CRF using a high-resolution X-ray tomographic system, i.e. microfocus computed tomography (MXCT), which is capable of detecting microscopic structural changes in bone tissue. METHODS: CRF rats were created by 7/8 nephrectomy by ligation of the renal artery branches, and were sacrificed 24 weeks after surgery. MXCT and bone mineral densitometry by single-energy X-ray absorptiometry (SXA) were performed using extracted bone samples. Images obtained by MXCT were further analyzed by node-strut morphometry. RESULTS: Biochemical analysis confirmed that CRF was induced in 7/8-renal artery-ligated rats. MXCT demonstrated a significant decrease in trabecular bone in uremic rats, whereas SXA was unable to detect the difference. The node-strut method revealed decreased trabecular connectivity, with little change in the thickness of the trabecular bone in uremic rats. CONCLUSION: MXCT was able to detect significant changes in trabecular bone at an early stage of renal failure. The observed structural changes differed from those found in long-term dialysis patients. MXCT is a practical and promising device used for the non-invasive evaluation of early bone changes in uremic patients.

Absorptiometry, Photon↗

PubMed2003

Vascular endothelial growth factor gene polymorphisms in Japanese patients with sarcoidosis.

OBJECTIVES: Vascular endothelial growth factor (VEGF) promotes angiogenesis, mediates vascular permeability, and activates and recruits monocytes. VEGF is produced in activated alveolar macrophages, in epithelioid cells, and in multinuclear giant cells of pulmonary sarcoid granulomas. Recent reports have shown that a polymorphism at - 627 of the VEGF gene is related to VEGF protein production, and a polymorphism at + 813 is associated with VEGF plasma levels. We investigated the roles of such polymorphisms in the development and extent of sarcoidosis. METHODS: We examined polymorphisms of the VEGF gene in 103 Japanese patients with sarcoidosis and 146 healthy Japanese control subjects. The position - 627 polymorphism was determined using the TaqMan (TaqMan Laboratory, University of Pittsburgh Cancer Institute; Pittsburgh, PA) polymerase chain reaction (PCR) method. For genotyping of the position + 813 polymorphism, the PCR restriction fragment length polymorphism method was performed. RESULTS: As for + 813 genotypes, the less-common genotypes CT and TT were found more often in control subjects than in patients (odds ratio, 0.490; 95% confidence interval, 0.276 to 0.868). A significant increase in the frequency of the T allele (p = 0.005, Pc = 0.020 after Bonferroni correction) was observed in control subjects. As for - 627 genotypes, the mean value of the FEV(1)/FVC percentage in GG type was lower than that in CC or CG type, however, the other clinical findings did not suggest airway diseases in the GG type. CONCLUSIONS: We suggest that in VEGF gene polymorphisms the T allele at + 813 may decrease susceptibility to sarcoidosis.

Adult↗

PubMed2003

Risk of periodontitis in systemic lupus erythematosus is associated with Fcgamma receptor polymorphisms.

BACKGROUND: Leukocyte Fc receptors for immunoglobulin G (FcgammaR) play a major role in the handling of immune complexes and pathogens in systemic lupus erythematosus (SLE) and periodontitis. Both diseases have been shown to be partly influenced by genetic components including FcgammaR genotype. The aim of this study was therefore to evaluate whether FcgammaR gene polymorphisms are associated with periodontitis risk in SLE patients. METHODS: The study subjects consisted of 42 SLE patients with periodontitis (SLE/P), 18 SLE patients without periodontitis (SLE/H), 42 healthy subjects with periodontitis (H/P), and 42 healthy subjects without periodontitis (H/H), who were all unrelated Japanese non-smokers. Genomic DNA was isolated from peripheral blood, and FcgammaR genotypes for 3 biallelic polymorphisms (FcgammaRIIa-R131/H131, FcgammaRIIIa-158V/158F, FcgammaRIIIb-NA1/NA2) were determined by allele-specific polymerase chain reactions. RESULTS: The SLE/P group was found to have more mild levels of periodontal destruction than the H/P group (P < 0.01). There was a significant difference in the distribution of FcgammaRIIa genotypes between SLE/P and H/H groups (P = 0.004). A significant overrepresentation of the FcgammaRIIa-R131 allele was found in the SLE/P group compared to the H/H group (SLE/P versus H/H: odds ratio [OR] 3.13, 95% confidence interval [CI] 1.46-6.77, P = 0.0013). Furthermore, the prevalence of periodontitis was found to be 70% in SLE patients. The FcgammaRIIa-R131 allele was also found to be overrepresented in the SLE/P group compared to the SLE/H group (SLE/P versus SLE/H: OR 3.40, 95% CI 1.18-10.25, P = 0.011). CONCLUSION: These results show the FcgammaRIIa-R131 allele to be associated with periodontitis risk in SLE patients.

Adolescent↗

PubMed2003

Four cases of pheochromocytoma in patients with end-stage renal disease.

Although pheochromocytoma in a patient with end-stage renal disease (ESRD) is considered extremely rare, we recently encountered 4 ESRD patients with pheochromocytoma. Three were symptomatic, and in the fourth patient the tumor was discovered as an adrenal incidentaloma. Plasma catecholamine levels were significantly increased in two patients. In each case, 131I-MIBG scintigraphy showed accumulation of the radionuclide in the adrenal tumor, which was identified by MRI or CT scanning, and adrenalectomy was conducted without serious complications. Although paroxysmal hypertension is a common symptom in patients with ESRD, pheochromocytoma must be eliminated by careful evaluation.

Adrenal Gland Neoplasms↗

PubMed2003

Adult onset anaphylactoid purpura with severe gastrointestinal involvement.

We treated a case of adult-onset severe-form anaphylactoid purpura. This case had been diagnosed as anaphylactoid purpura pathologically by skin biopsy. However, his clinical manifestations were atypical in view of complicated massive gastrointestinal hemorrhage. Intensive therapy including corticosteroid and cyclophosphamide transiently improved his condition. Nevertheless, the beta-D-glucan value in peripheral blood was gradually elevated. Prophylactic use of fluconazole failed to prevent contraction of invasive mycosis. Finally, he suddenly suffered from diffuse cerebral hemorrhage. Postmortem examination revealed systemic invasive aspergillosis as the cause of death.

Age of Onset↗

PubMed2003

A patient with Takayasu's arteritis treated with corticosteroids who developed primary biliary cirrhosis.

A 40-year-old woman with a history of fever and arthralgia since age 17 had received long-term prednisolone (PSL) therapy. She was diagnosed with Takayasu's arteritis in 1980 and given PSL. The symptoms were well controlled until she developed itching in 1998. Laboratory tests showed elevated levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyltranspeptidase, total cholesterol, and immunoglobulin M (IgM). She tested positive for anti-mitochondria antibody and for both IgG and IgM anti-pyruvate dehydrogenases. Liver biopsy findings were typical of primary biliary cirrhosis (PBC). Our patient's clinical course suggested that an adequate amount of PSL to control Takayasu's arteritis does not necessarily prevent the development of PBC.

Adult↗

PubMed2003

[Two cases of interstitial pneumonia with anti-Jo-1 antibodies in the absence of myositis].

We present two cases of interstitial pneumonia with anti-Jo-1 antibodies in the absence of myositis. The first patient was a 38-year-old woman and the second, a 59-year-old woman. Both patients were admitted to our hospital complaining of dry cough and dyspnea on effort. The diagnosis of interstitial pneumonia was made from chest radiography, computed tomography and surgical lung biopsy. Anti-Jo-1 antibodies, which were highly specific for polymyositis and dermatomyositis (PM/DM), were detected in both patients. However, the serum creatine kinase concentrations and electromyographic findings in both patients were normal, and no clinical signs (including muscle weakness, rash and arthralgia) were found. In the first patient, oral prednisolone (PSL) treatment (20 mg day) improved the interstitial pneumonia, but PSL has now been tapered to 17.5 mg day. In the second patient, oral PSL treatment (40 mg day) improved interstitial pneumonia, and the dose was tapered to 5 mg day. The second patient was followed for more than 10 years after treatment, but she has never shown any signs of clinical myositis. Further investigation will be required, because no pathophysiological relation between anti-Jo-1 antibodies and interstitial pneumonia with PM DM has yet been established.

Adult↗

PubMed2003

[Cyclosporin improved pure red cell aplasia associated with thymoma and tended to decrease thymoma size: a case report].

The case was a 56-year-old man who underwent extended thymothymectomy in 1993 because of an invasive thymoma classified as Masaoka IIa. The tumor was disseminated through the right thoracic cavity in 1994. Although the chemotherapy was repeated, the disseminated thymoma tended to increase in size. The patient was suffering from severe anemia, and pure red cell aplasia was diagnosed in September 2002. The administration of cyclosporin was initiated, and not only brought about improvement of pure red cell aplasia but also tended to shrink the thymoma. Cyclosporin may be an effective drug for the reduction of thymoma as well as for pure red cell aplasia.

Cyclosporins↗

PubMed2003

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2001)].

From October 2001 to September 2002, we collected the specimen from 370 patients with lower respiratory tract infections in 16 institutions in Japan, and investigated the susceptibilities of the isolated bacteria to various antibacterial agents and antibiotics and patients' characteristics. Of 458 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 456 strains were investigated. The breakdown of the isolated bacteria were: Staphylococcus aureus 69, Streptococcus pneumoniae 72, Haemophilus influenzae 85, Pseudomonas aeruginosa (non-mucoid) 44, P. aeruginosa (mucoid) 13, Klebsiella pneumoniae 32, Moraxella subgenus Branhamella catarrhalis 32, and others. Of 69 S. aureus strains, those with 4 micrograms/mL or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) occupied 43.5%. Vancomycin and arbekacin showed the most potent activities against MRSA as observed in 2000. The frequency of S. pneumoniae exhibiting low sensitivity to penicillin (penicillin-intermediate S. pneumoniae: PISP + penicillin-resistant S. pneumoniae: PRSP) was 59.7% and both rates of PISP and PRSP were the highest after 1992. Carbapenems had strong activities against S. pneumoniae. Especially, panipenem and imipenem inhibited the growth of all 72 strains at 0.125 and 0.5 microgram/mL, respectively. Generally, all drugs had strong activities against H. influenzae with MIC90s of 16 micrograms/mL or less. The drug that had the strongest activity against H. influenzae was levofloxacin, which inhibited the growth of 80 of the 85 strains at 0.063 microgram/mL. Against P. aeruginosa mucoid strain, meropenem had a strong activity with MIC90 of 0.5 microgram/mL while, against non-mucoid strain, tobramycin had a strong activity with MIC90 of 2 micrograms/mL. K. pneumoniae showed good susceptibilities to all drugs except ampicillin and minocycline, and the MIC90s were 4 micrograms/mL or less. Particularly, cefmenoxime, cefpirome, and imipenem had the strongest activity (MIC90: 0.125 microgram/mL), and cefozopran had a strong activity, inhibiting the growth of all strains at 0.25 microgram/mL. Also, all drugs generally had strong activities against M. (B.) catarrhalis. MIC90s of all drugs were 4 micrograms/mL or less. The drug that had the strongest activity was minocycline and levofloxacin inhibiting all 32 strains at 0.063 microgram/mL. Most of the patients with respiratory infection were aged 70 years or older, accounting for approximately a half of the total (40.5%). As for the incidence by the diseases, bacterial pneumonia and chronic bronchitis were the highest, being noted in 39.2% and 37.3% of all the patients, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (19.3%) and S. pneumoniae (19.9%). In contrast, H. influenzae (22.0%) were frequently isolated from the patients with chronic bronchitis. Before the drug administration, the bacteria frequently isolated from the patients were S. pneumoniae (20.8%) and H. influenzae (21.5%). S. pneumoniae and H. influenzae decreased after the initiation of drug administration while S. aureus increased. The isolation frequency of P. aeruginosa was higher after than before the initiation of drug administration. The bacteria were frequently isolated from the patients who had already treated with cephems were S. aureus and P. aeruginosa. From the patients who had already treated with macrolides, S. pneumoniae was the most frequently isolated while S. aureus was the most frequently isolated from the patients pre-treated with quinolones.

Adult↗

PubMed2003

[Kidney transplantation and bone].

Osteoporosis, renal osteodystrophy and osteoarthropathy derived from hemodialysis associated amyloidosis are three major bone diseases after the kidney transplantation. Osteoporosis that is induced by steroid administration is an inevitable side effect and develops more frequently in the elderly recipients. After the recovery of renal function due to grafted kidney, secondary hyperparathyroidism usually improves and the serum level of PTH-intact downs to the almost normal range. However, the patients who have tertiary hyperparathyroidism are unable to show the enough lowering of PTH-intact. In these cases, renal osteodystrophy progresses even though kidney grafts have fine renal function. Osteoarthropathy derived from hemodialysis associated amyloidosis reveals distinct clinical courses depending to the types of diseases. Some of them improve and the remained ones become worse. After the kidney transplantation we must keep to concern for the bone condition of grafted patients.

English Abstract↗

PubMed2002

Establishment of a first-order kinetic model of light chain-associated amyloid fibril extension in vitro.

Light chain-associated (AL) amyloidosis is a common and fatal systemic amyloidosis. AL amyloid fibrils (fAL) are composed of intact or fragmental monoclonal light chains (AL proteins). To elucidate the molecular mechanisms of fAL formation from AL proteins, we purified fAL and AL proteins from the amyloid-deposited organs of five AL amyloidosis patients. By electron microscopy and fluorometric thioflavin T method, we observed optimal fibril extension at pH 2.0-3.5 for the fibrils obtained from four patients, while at pH 7.5-8.0 for those obtained from one patient. Fragmental AL proteins were more efficient in the extension reaction than intact AL proteins. The fibrils obtained from all five patients showed clear fibril extension electron microscopically at pH 7.5. The extension of the fibrils obtained from all five patients could be explained by a first-order kinetic model, i.e., fibril extension proceeds via the consecutive association of AL proteins onto the ends of existing fibrils. Fibril extension was accelerated by dermatan sulfate proteoglycan, and inhibited by apolipoprotein E, alpha1-microglobulin, fibronectin, and an antioxidant nordihydroguaiaretic acid. These findings contribute to our understanding of the molecular mechanism underlying the pathogenesis of AL amyloidosis, and will be useful for developing a therapeutic strategy against the disease.

Adult↗