The immune system is a complex network of cells with critical functions in health and disease. Ho... more The immune system is a complex network of cells with critical functions in health and disease. However, a comprehensive census of the cells comprising the immune system is lacking. Here, we estimated the abundance of the primary immune cell types throughout all tissues in the human body. We conducted a literature survey and integrated data from multiplexed imaging and methylome-based deconvolution. We also considered cellular mass to determine the distribution of immune cells in terms of both number and total mass. Our results indicate that the immune system of a reference 73 kg man consists of 1.8 × 10 12 cells (95% CI 1.5–2.3 × 10 12 ), weighing 1.2 kg (95% CI 0.8–1.9). Lymphocytes constitute 40% of the total number of immune cells and 15% of the mass and are mainly located in the lymph nodes and spleen. Neutrophils account for similar proportions of both the number and total mass of immune cells, with most neutrophils residing in the bone marrow. Macrophages, present in most tiss...
Journal of Pediatric Endocrinology and Metabolism, Apr 16, 2021
Objectives Hyperinsulinism is the most common cause of recurrent hypoglycemia in infants, with tr... more Objectives Hyperinsulinism is the most common cause of recurrent hypoglycemia in infants, with transient and permanent forms. Currently, there are no effective tools to predict severity and time to resolution in infants with transient hyperinsulinism (tHI). Therefore, our objective was to assess whether early glucose trends predict disease duration in tHI. Methods A retrospective, pilot cohort of infants admitted with tHI was phenotyped for clinical and laboratory parameters. Blood glucose (BG) values were collected from the first documented hypoglycemia for 120 h (five days). Results In 27 neonates with tHI, the presence of fetal distress (p=0.001) and higher mean daily BG (p=0.035) were associated with shorter time to resolution of hypoglycemia. In a further sensitivity analysis that grouped the cohort by the presence or absence of fetal distress, we found that in neonates without fetal distress, lower mean daily glucose was associated with longer disease duration (R2=0.53, p=0.01). Conclusions Our pilot data suggests that predictors for disease duration of tHI may be elicited in the first week of life, and that tHI associated with fetal distress may represent a distinct clinical entity with a shorter time course.
OBJECTIVE In polycythemia vera (PV) there is no specific clonal marker because the molecular lesi... more OBJECTIVE In polycythemia vera (PV) there is no specific clonal marker because the molecular lesion responsible for PV is unknown. The recent demonstration that the PRV-1 gene is overexpressed in granulocytes from patients with PV provided the rationale for the current study to investigate whether PRV-1 is structurally rearranged, thus explaining its aberrant expression. MATERIALS AND METHODS Fluorescence in situ hybridization was used to determine chromosomal localization of PRV-1 and to study whether the PRV1 gene is rearranged in 26 patients with PV. RESULTS PRV-1 was localized to chromosome 19, band region q13.12-2. Structural rearrangements of PRV-1 were evaluated in bone marrow cells from 26 patients with PV: 14 with a normal karyotype and 12 with an abnormal karyotype. None of 150 metaphase cells or more than 10,000 interphase cells demonstrated PRV-1 gene deletion, amplification, or separation of the probe signal, which would indicate a PRV-1 rearrangement. CONCLUSION These findings are consistent with a lack of structural rearrangement of PRV-1 in patients with PV. Thus, overexpression of PRV-1 in granulocytes from patients with PV is related to mechanisms that do not involve structural genetic changes.
<p>Back of the envelope estimate of the number of cells in an adult human body based on a c... more <p>Back of the envelope estimate of the number of cells in an adult human body based on a characteristic volume and mass.</p
Journal of Pediatric Endocrinology and Metabolism, 2021
Objectives Hyperinsulinism is the most common cause of recurrent hypoglycemia in infants, with tr... more Objectives Hyperinsulinism is the most common cause of recurrent hypoglycemia in infants, with transient and permanent forms. Currently, there are no effective tools to predict severity and time to resolution in infants with transient hyperinsulinism (tHI). Therefore, our objective was to assess whether early glucose trends predict disease duration in tHI. Methods A retrospective, pilot cohort of infants admitted with tHI was phenotyped for clinical and laboratory parameters. Blood glucose (BG) values were collected from the first documented hypoglycemia for 120 h (five days). Results In 27 neonates with tHI, the presence of fetal distress (p=0.001) and higher mean daily BG (p=0.035) were associated with shorter time to resolution of hypoglycemia. In a further sensitivity analysis that grouped the cohort by the presence or absence of fetal distress, we found that in neonates without fetal distress, lower mean daily glucose was associated with longer disease duration (R2=0.53, p=0.01...
A GLP-2 analogue is used in individuals with intestinal failure at risk for liver disease, yet th... more A GLP-2 analogue is used in individuals with intestinal failure at risk for liver disease, yet the hepatic actions of GLP-2 are not understood. Treatment of high fat diet (HFD)-fed mice with GLP-2 did not modify the development of hepatosteatosis or hepatic inflammation. In contrast, Glp2r-/- mice exhibited increased hepatic lipid accumulation, deterioration in glucose tolerance, and upregulation of biomarkers of hepatic inflammation. Both mouse and human liver expressed the canonical GLP-2R, and hepatic Glp2r expression was upregulated in mice with hepatosteatosis. Cell fractionation localized the Glp2r to hepatic stellate cells (HSC), and markers of HSC activation and fibrosis were increased in livers from Glp2r-/- mice. Moreover, GLP-2 directly modulated gene expression in isolated HSCs ex vivo. Taken together, these findings define an essential role for the GLP-2R in hepatic adaptation to nutrient excess and unveil a gut hormone-HSC axis, linking GLP-2R signaling to control of h...
The immune system is a complex network of cells with critical functions in health and disease. Ho... more The immune system is a complex network of cells with critical functions in health and disease. However, a comprehensive census of the cells comprising the immune system is lacking. Here, we estimated the abundance of the primary immune cell types throughout all tissues in the human body. We conducted a literature survey and integrated data from multiplexed imaging and methylome-based deconvolution. We also considered cellular mass to determine the distribution of immune cells in terms of both number and total mass. Our results indicate that the immune system of a reference 73 kg man consists of 1.8 × 10 12 cells (95% CI 1.5–2.3 × 10 12 ), weighing 1.2 kg (95% CI 0.8–1.9). Lymphocytes constitute 40% of the total number of immune cells and 15% of the mass and are mainly located in the lymph nodes and spleen. Neutrophils account for similar proportions of both the number and total mass of immune cells, with most neutrophils residing in the bone marrow. Macrophages, present in most tiss...
Journal of Pediatric Endocrinology and Metabolism, Apr 16, 2021
Objectives Hyperinsulinism is the most common cause of recurrent hypoglycemia in infants, with tr... more Objectives Hyperinsulinism is the most common cause of recurrent hypoglycemia in infants, with transient and permanent forms. Currently, there are no effective tools to predict severity and time to resolution in infants with transient hyperinsulinism (tHI). Therefore, our objective was to assess whether early glucose trends predict disease duration in tHI. Methods A retrospective, pilot cohort of infants admitted with tHI was phenotyped for clinical and laboratory parameters. Blood glucose (BG) values were collected from the first documented hypoglycemia for 120 h (five days). Results In 27 neonates with tHI, the presence of fetal distress (p=0.001) and higher mean daily BG (p=0.035) were associated with shorter time to resolution of hypoglycemia. In a further sensitivity analysis that grouped the cohort by the presence or absence of fetal distress, we found that in neonates without fetal distress, lower mean daily glucose was associated with longer disease duration (R2=0.53, p=0.01). Conclusions Our pilot data suggests that predictors for disease duration of tHI may be elicited in the first week of life, and that tHI associated with fetal distress may represent a distinct clinical entity with a shorter time course.
OBJECTIVE In polycythemia vera (PV) there is no specific clonal marker because the molecular lesi... more OBJECTIVE In polycythemia vera (PV) there is no specific clonal marker because the molecular lesion responsible for PV is unknown. The recent demonstration that the PRV-1 gene is overexpressed in granulocytes from patients with PV provided the rationale for the current study to investigate whether PRV-1 is structurally rearranged, thus explaining its aberrant expression. MATERIALS AND METHODS Fluorescence in situ hybridization was used to determine chromosomal localization of PRV-1 and to study whether the PRV1 gene is rearranged in 26 patients with PV. RESULTS PRV-1 was localized to chromosome 19, band region q13.12-2. Structural rearrangements of PRV-1 were evaluated in bone marrow cells from 26 patients with PV: 14 with a normal karyotype and 12 with an abnormal karyotype. None of 150 metaphase cells or more than 10,000 interphase cells demonstrated PRV-1 gene deletion, amplification, or separation of the probe signal, which would indicate a PRV-1 rearrangement. CONCLUSION These findings are consistent with a lack of structural rearrangement of PRV-1 in patients with PV. Thus, overexpression of PRV-1 in granulocytes from patients with PV is related to mechanisms that do not involve structural genetic changes.
<p>Back of the envelope estimate of the number of cells in an adult human body based on a c... more <p>Back of the envelope estimate of the number of cells in an adult human body based on a characteristic volume and mass.</p
Journal of Pediatric Endocrinology and Metabolism, 2021
Objectives Hyperinsulinism is the most common cause of recurrent hypoglycemia in infants, with tr... more Objectives Hyperinsulinism is the most common cause of recurrent hypoglycemia in infants, with transient and permanent forms. Currently, there are no effective tools to predict severity and time to resolution in infants with transient hyperinsulinism (tHI). Therefore, our objective was to assess whether early glucose trends predict disease duration in tHI. Methods A retrospective, pilot cohort of infants admitted with tHI was phenotyped for clinical and laboratory parameters. Blood glucose (BG) values were collected from the first documented hypoglycemia for 120 h (five days). Results In 27 neonates with tHI, the presence of fetal distress (p=0.001) and higher mean daily BG (p=0.035) were associated with shorter time to resolution of hypoglycemia. In a further sensitivity analysis that grouped the cohort by the presence or absence of fetal distress, we found that in neonates without fetal distress, lower mean daily glucose was associated with longer disease duration (R2=0.53, p=0.01...
A GLP-2 analogue is used in individuals with intestinal failure at risk for liver disease, yet th... more A GLP-2 analogue is used in individuals with intestinal failure at risk for liver disease, yet the hepatic actions of GLP-2 are not understood. Treatment of high fat diet (HFD)-fed mice with GLP-2 did not modify the development of hepatosteatosis or hepatic inflammation. In contrast, Glp2r-/- mice exhibited increased hepatic lipid accumulation, deterioration in glucose tolerance, and upregulation of biomarkers of hepatic inflammation. Both mouse and human liver expressed the canonical GLP-2R, and hepatic Glp2r expression was upregulated in mice with hepatosteatosis. Cell fractionation localized the Glp2r to hepatic stellate cells (HSC), and markers of HSC activation and fibrosis were increased in livers from Glp2r-/- mice. Moreover, GLP-2 directly modulated gene expression in isolated HSCs ex vivo. Taken together, these findings define an essential role for the GLP-2R in hepatic adaptation to nutrient excess and unveil a gut hormone-HSC axis, linking GLP-2R signaling to control of h...
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Papers by Shai Fuchs