Neil David Theise

• Professor at NYU Langone Medical Center

The absence of a clear consensus on the definition and significance of fascia and the indiscriminate use of the term throughout the clinical and scientific literature has led to skepticism regarding its importance in the human body. To address this challenge, we propose that: (1) fasciae, and the fascial interstitia within them, constitute an anato...

Biliary atresia is a neonatal disease characterized by damage, inflammation, and fibrosis of the liver and bile ducts and by abnormal bile metabolism. It likely results from a prenatal environmental exposure that spares the mother and affects the fetus. Our aim was to develop a model of fetal injury by exposing pregnant mice to low-dose biliatreson...

Background & aims: Glisson's capsule is the interstitial connective tissue that surrounds the liver. As part of its normal physiology, it withstands significant daily changes in liver size. The pathophysiology of the capsule in disease is not well understood. The aim of this study was to characterise the changes in capsule matrix, cellular composi...

Franklin Mall was one of the foremost scientists of the turn of the 19th century, an exemplary mentor as well as researcher, and his revolutionary contributions are still relevant today. Mall's early training in Leipzig with Wilhelm His and Carl Ludwig provided him with an unusual perspective on the integration of anatomy and physiology, and his in...

Background & Aims Biliary atresia is a neonatal disease characterized by bile duct and liver damage, fibrosis, inflammation and abnormal bile metabolism. It appears to result from a prenatal exposure that spares the mother and affects the fetus. Our aim was to define the phenotype in neonatal mice after maternal exposure to low-dose biliatresone, a...

Background and Aims Glisson’s capsule is the interstitial connective tissue that surrounds the liver. As part of its normal physiology, it withstands significant daily changes in liver size. The pathophysiology of the capsule in disease is not well understood. The aim of this study was to characterize the changes in capsule matrix, cellular composi...

Hepatocellular carcinoma (HCC), a major global contributor of cancer death, usually arises in a background of chronic liver disease, as a result of molecular changes that deregulate important signal transduction pathways. Recent studies have shown that certain molecular changes of hepatocarcinogenesis are associated with clinicopathologic features...

Cerebrospinal fluid (CSF), predominantly produced in the ventricles and circulating throughout the brain and spinal cord, is a key protective mechanism of the central nervous system (CNS). Physical cushioning, nutrient delivery, metabolic waste, including protein clearance, are key functions of the CSF in humans. CSF volume and flow dynamics regula...

Bodies have continuous reticular networks, comprising collagens, elastin, glycosaminoglycans, and other extracellular matrix components, within and around all organs. Fibrous tissue coverings of nerves and blood vessels create structural continuity beyond organ boundaries. We recently validated fluid flow through human fibrous tissues, though wheth...

Background In sporadic Alzheimer’s disease (AD), brain amyloid-beta (Aβ) deposition is believed to be a consequence of impaired Aβ clearance, but this relationship is not well established in living humans. CSF clearance, a major feature of brain glymphatic clearance (BGC), has been shown to be abnormal in AD murine models. MRI phase contrast and in...

The gut microbiome shapes local and systemic immunity. The liver is presumed to be a protected sterile site. As such, a hepatic microbiome has not been examined. Here, we showed a liver microbiome in mice and humans that is distinct from the gut and is enriched in Proteobacteria. It undergoes dynamic alterations with age and is influenced by the en...

Despite significant research efforts, treatment options for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain limited. This is due in part to a lack of therapeutics that increase host defense to the virus. Replication of SARS-CoV-2 in lung tissue is associated with marked infiltration of macrophages and activation of innate immune...

Huanglongbing (citrus greening) is caused by the unculturable, gram negative bacterium Liberibacter asiaticus and transmitted by the Asian Citrus Psyllid ( Diaphorina citri ). Prior research demonstrated that the rifampicin-derivative TPR-1 as well as Palisades Therapeutic (PT) compounds PT159 and PT160 were effective at inhibiting growth of the L....

Objectives: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may develop end-stage lung disease requiring lung transplantation. We report the clinical course, pulmonary pathology with radiographic correlation, and outcomes after lung transplantation in three patients who developed chronic respiratory failure due...

The human brain functions at the center of a network of systems aimed at providing a structural and immunological layer of protection. The cerebrospinal fluid (CSF) maintains a physiological homeostasis that is of paramount importance to proper neurological activity. CSF is largely produced in the choroid plexus where it is continuous with the brai...

Hepatocellular carcinoma (HCC) is a malignancy with variable biologic aggressiveness based on the tumor grade, presence or absence of vascular invasion, and pathologic and molecular classification. Knowledge and understanding of the prognostic implications of different pathologic and molecular phenotypes of HCC are emerging, with therapeutics that...

Background: Lymphoepithelioma-like carcinomas (LELCs) are uncommon epithelial cancers characteristically showing two distinct components consisting of malignant epithelial cells and prominent dense lymphoid infiltrate. Hepatic LELCs consist of two types, the lymphoepithelioma-like hepatocellular carcinoma and lymphoepithelioma-like cholangiocarcin...

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In sporadic Alzheimer’s disease (AD), brain amyloid-beta (Aβ) deposition is believed to be a consequence of impaired Aβ clearance, but this relationship is not well established in living human subjects. CSF clearance, a major feature of brain glymphatic clearance (BGC), has been shown to be abnormal in AD murine models. Prior MRI phase contrast stu...

In the background of chronic liver disease, hepatocellular carcinoma develops via a complex, multistep process called hepatocarcinogenesis. This article reviews the causes contributing to the process. Emphasis is made on the imaging manifestations of the pathologic changes seen at many stages of hepatocarcinogenesis, from regenerative nodules to dy...

Introduction: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 virus, is a predominantly respiratory tract infection with the capacity to affect multiple organ systems. Abnormal liver tests, mainly transaminase elevations, have been reported in hospitalized patients. We describe a syndrome of cholangio...

Bodies have continuous reticular networks, comprising collagens, elastin, glycosaminoglycans, and other extracellular matrix components, through all tissues and organs. Fibrous coverings of nerves and blood vessels create structural continuity beyond organ boundaries. We recently validated fluid flow through human fibrous tissues, though whether th...

Gastrointestinal (GI) symptoms of SARS-CoV-2/COVID-19 in the form of anorexia, nausea, vomiting, abdominal pain and diarrhea are usually preceded by respiratory manifestations and are associated with a poor prognosis. Hematochezia is an uncommon clinical presentation of COVID-19, and we hypothesize that older patients with significant comorbidities...

Since its initial discovery in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of COVID19, has spread worldwide and despite significant research efforts, treatment options remain limited. Replication of SARS-CoV-2 in lung is associated with marked infiltration of macrophages and activation of innate immune inflamm...

Advanced non-alcoholic fatty liver disease (NAFLD) is a rapidly emerging global health problem associated with pre-disposing genetic polymorphisms, most strikingly an isoleucine to methionine substitution in patatin-like phospholipase domain-containing protein 3 (PNPLA3-I148M). Here, we study how human hepatocytes with PNPLA3 148I and 148M variants...

PT150 is a clinical-stage molecule, taken orally, with a strong safety profile having completed Phase 1 and Phase 2 clinical trials for its original use as an antidepressant. It has an active IND for COVID-19. Antiviral activities have been found for PT150 and other members of its class in a variety of virus families; thus, it was now tested agains...

Advanced non-alcoholic fatty liver disease (NAFLD) is a rapidly emerging global health problem associated with pre-disposing genetic polymorphisms, most strikingly an isoleucine to methionine substitution in patatin-like phospholipase domain-containing protein 3 (PNPLA3-I148M). Here, we study how human hepatocytes with PNPLA3 148I and 148M variants...

Multiplexed immunohistochemical techniques give insight into contextual cellular relationships by offering the ability to collect cell-specific data with spatial information from formalin-fixed, paraffin-embedded tissue sections. We established an automated sequential elution-stripping multiplex immunohistochemical assay to address two controversia...

The autonomic nervous system plays a role in a variety of liver regenerative and metabolic functions, including modulating bile secretion and cholangiocyte and hepatobiliary progenitors of the canals of Hering. However, the nature and location of nerves which link to the proximal biliary tree have remained uncertain. We investigate the anatomic rel...

Gastrointestinal (GI) symptoms of SARS-CoV2/COVID-19 in the form of anorexia,nausea, vomiting, abdominal pain and diarrhea are usually preceeded by respiratory manifestations and are associated with a poor prognosis. Hematochezia is an uncommon clinical presentation of COVID-19 disease and we hypothesize that older patients with significant comorbi...

Bodies have "reticular networks" comprising collagens, elastin, glycosaminoglycans, and other extracellular matrix components, that are continuous within and around all organs. Fibrous tissue coverings of nerves and blood vessels create structural continuity beyond organ boundaries. We recently described fluid flow through such human fibrous tissue...

PT150 is a clinical stage molecule, taken orally, with a strong safety profile having completed Phase 1 and Phase 2 clinical trials for its original use as an anti-depressant. It has an active IND for COVID-19. Antiviral activities have been found for PT150 and other members of its class in a variety of virus families; thus, it was now tested again...

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer death in the world. Although most cases occur in stiff, cirrhotic livers, and stiffness is a significant risk factor, HCC can also arise in non-cirrhotic livers in the setting of non-alcoholic fatty liver disease (NAFLD). We hypothesized that lipid droplets in NAFLD might apply me...

e15663 Background: Large public cancer databases have allowed identification of novel mechanisms of oncogenesis and development of pharmacotherapies targeting these pathways. Examples are the androgen receptor (AR) and glucocorticoid receptor (GR). The Cancer Genome Atlas (TCGA) shows these receptors to have significantly increased expression over...

Multiplexed immunohistochemical techniques give insight into contextual cellular relationships by offering the ability to collect cell-specific data with spatial information from formalin-fixed, paraffin embedded tissue sections. We established an automated sequential elution-stripping multiplex immunohistochemical assay to address two controversia...

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer death in the world. Although most cases occur in stiff, cirrhotic livers, and stiffness is a significant risk factor, HCC can also arise in non-cirrhotic livers in the setting of non-alcoholic fatty liver disease (NAFLD). We hypothesized that lipid droplets in NAFLD might apply me...

Background & Aims Progression of liver fibrosis still occurs in some patients with chronic hepatitis B virus (HBV) infection despite antiviral therapy. We aimed to identify risk factors for fibrosis progression in patients who received antiviral therapy. Methods We conducted a longitudinal study of patients with chronic HBV infection and liver bio...

Primary human hepatocytes (PHHs) are an essential tool for modeling drug metabolism and liver disease. However, variable plating efficiencies, short lifespan in culture, and resistance to genetic manipulation have limited their use. Here, we show that the pyrrolizidine alkaloid retrorsine improves PHH repopulation of chimeric mice on average 10-fol...

Background & aims: The extrahepatic bile duct is the primary tissue initially affected by the cholangiopathy biliary atresia. Biliary atresia affects neonates exclusively and current animal models suggest that the developing bile duct is uniquely susceptible to damage. In this study, we aimed to define the anatomical and functional differences bet...

Ductular reaction (DR) is observed in virtually all liver diseases in both humans and rodents. Depending on the injury, DR is confined within the periportal area or invades the parenchyma. On severe hepatocellular injury, invasive DR has been proposed to arise for supplying the liver with new hepatocytes. However, experimental data evidenced that D...

Background & Aims The extrahepatic bile duct is the primary tissue initially affected by the cholangiopathy biliary atresia. Biliary atresia affects neonates exclusively and current animal models suggest that the developing bile duct is uniquely susceptible to damage. In this study, we aimed to define the anatomical and functional differences betwe...

Idiopathic non‐cirrhotic portal hypertension (INCPH) is a rare vascular liver disease that has attained a new interest in recent years. It is characterized by clinical signs of portal hypertension in the absence of cirrhosis or severe fibrosis and any known cause of portal hypertension. Since much uncertainty exists about INCPH pathophysiology and...

Cirrhosis has been traditionally viewed as an irreversible, end-stage condition. Eighteen years ago, Wanless, Nakashima, and Sherman published a study that was based on the concept that hepatic architecture is under constant remodeling in the course of chronic liver diseases, even during their most advanced stages; depending on the balance between...

Introduction. “Acute-on-Chronic-Liver Failure (ACLF)” entered hepatology practice by the end of the 20th century. Although we lack precise and universally agreed definitions, acute decompensation of chronic liver disease with jaundice and deranged clotting, multi-organ failure and high, short-term mortality are hallmarks of the syndrome. Timely rec...

Background & rationale: High-mobility group box-1 (HMGB1) is a damage-associated molecular pattern (DAMP) increased in response to liver injury. Since HMGB1 is a ligand for the receptor for advanced glycation end-products (RAGE), we hypothesized that induction of HMGB1 could participate in the pathogenesis of liver fibrosis via RAGE cell-specific...

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Tenofovir alafenamide induced liver failure: The objective of our case report is to present a rare case of tenofovir alafenamide (TAF) induced liver failure. TAF has been widely used for hepatitis B infection since its release in 2016. Our patient is a 56 year old male with chronic hepatitis B cirrhosis who was switched from tenofovir disoproxil fu...

In this new era of successful long term suppression of hepatitis B viral replication and consistent eradication of hepatitis C virus the necessity for routine pre-treatment biopsies has often been eliminated. Thus, whether there is utility to perform liver biopsy in chronic viral hepatitis is undergoing re-examination. In response to these changing...

Confocal laser endomicroscopy (pCLE) provides real-time histologic imaging of human tissues at a depth of 60-70 μm during endoscopy. pCLE of the extrahepatic bile duct after fluorescein injection demonstrated a reticular pattern within fluorescein-filled sinuses that had no known anatomical correlate. Freezing biopsy tissue before fixation preserve...

Current widely used semiquantitative histological assessment methods are insensitive to identify subtle changes of liver fibrosis. Therefore, to precisely assess therapeutic efficacy on chronic hepatitis B (CHB), we explored the utility of qFibrosis (a fully-quantitative morphometric method employing second harmonic generation/two photon excitation...

Primary liver carcinomas with both hepatocytic and cholangiocytic differentiation have been referred to as "combined (or mixed) hepatocellular-cholangiocarcinoma." These tumors, although described over 100 years ago, have attracted greater attention recently because of interest in possible stem cell origin and perhaps because of greater frequency a...

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Objectives: Investigate subtle fibrosis similarities and differences in adult and pediatric nonalcoholic fatty liver disease (NAFLD) using second harmonic generation (SHG). Methods: SHG/two-photon excitation fluorescence imaging quantified 100 collagen parameters and determined qFibrosis values by using the nonalcoholic steatohepatitis (NASH) Cl...

The liver is a unique organ for homeostasis with regenerative capacities. Hepatocytes possess a remarkable capacity to proliferate upon injury; however, in more severe scenarios liver regeneration is believed to arise from at least one, if not several facultative hepatic progenitor cell (HPC) compartments. Newly-identified pericentral stem/progenit...

Liver fibrosis is the net result of dynamic changes between fibrogenesis and fibrolysis. Evidence has shown that antiviral therapy can reverse liver fibrosis or even early cirrhosis caused by hepatitis B virus. However, current evaluation systems mainly focus on the severity of, but not the dynamic changes in, fibrosis. Here, we propose a new class...

Background and aims: Current modalities for lymph node staging in cancer can be limited. We sought to evaluate the feasibility of needle-based confocal laser endomicroscopy (nCLE) at the time of endoscopic ultrasound (EUS) and to describe the nCLE features that distinguish between benign, malignant, and inflammatory lymph nodes. Methods: We coll...

From 1990 to present, 14 liver pathologists and 2 clinical hepatologists from 9 countries have met annually to hold thematic 2.5-day meetings centered on case-based discussion. The goal of these meetings has been to identify gaps in knowledge in our field and fuel scholarly effort to address these gaps. The founding principles were worldwide repres...

The ontologic framework of Fundamental Awareness proposed here assumes that non-dual Awareness is foundational to the universe, not arising from the interactions or structures of higher level phenomena. The framework allows comparison and integration of views from the three investigative domains concerned with the understanding nature of consciousn...

Clinicopathological concepts on acute and chronic liver disease have rapidly evolved over the last few years, with advances in general and specific treatment options, and improved patient outcomes. The old paradigm of "irreversibility" of cirrhosis had been challenged in major ways, and the validity of the usage of the term "cirrhosis" has come int...

Objective: Liver fibrosis is associated with significant collagen-I deposition largely produced by activated hepatic stellate cells (HSCs); yet, the link between hepatocyte damage and the HSC profibrogenic response remains unclear. Here we show significant induction of osteopontin (OPN) and high-mobility group box-1 (HMGB1) in liver fibrosis. Sinc...

This article briefly reviews the biofield hypothesis and its scientific literature. Evidence for the existence of the biofield now exists, and current theoretical foundations are now being developed. A review of the biofield and related topics from the perspective of physical science is needed to identify a common body of knowledge and evaluate pos...

Neil Theise speaks to Georgia Patey, Commissioning Editor: Neil Theise is a diagnostic liver pathologist, adult stem cell researcher and complexity theorist in New York City, where he is a Professor of Pathology at the Mount Sinai Beth Israel Medical Center of Icahn School of Medicine at Mount Sinai. He received his medical degree from Columbia Uni...

Primary hepatic “lymphoepithelioma-like” carcinomas are very rare. The majority are cholangiocarcinomas, most of which are also associated with Epstein-Barr virus (EBV) infection by staining for viral proteins and/or RNA. Here we report a “lymphoepithelioma-like” biliary lesion with EBV infection with uncertain or low malignant potential. A 72-year...

A large number of cancer stem cells (CSC) were identified and characterized; however, the origins and formation of CSC remain elusive. Here, we examined the origination of the newly-identified CD34+ liver CSC (LCSC). We found that CD34+ LCSC co-expressed liver stem cell and myelomonocytic cell markers, showing a mixed phenotype, a combination of he...

Recent WHO classification for combined hepatocellular–cholangiocarcinoma and recognized stem cell subtypes has increased attention to such tumors; however, the resulting burst of reporting and research indicates that this classification, while provocative, is incomplete for description of the full array of primary liver carcinomas with biphenotypic...

A large number of cancer stem cells (CSC) have been isolated and identified; however, none has been cultured in an unlimited manner in vitro without losing tumorigenicity and multipotency. Here we successfully clonogenically cultured a newly identified CD34+ liver CSC (LCSC) on feeder cells up to 22 passages (to date) without losing CSC property. C...

CD34+ stem cells play an important role during liver development and regeneration. Thus, we hypothesized that some human liver carcinomas (HLCs) might be derived from transformed CD34+ stem cells. Here we determined that a population of CD34+ cells isolated from PLC/PRF/5 hepatoma cells (PLC) appears to function as liver cancer stem cells (LCSC) by...

Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein, which is frequently and highly expressed on carcinomas, tumor-initiating cells, selected tissue progenitors, embryonic and adult stem cells. During liver development, EpCAM demonstrates a dynamic expression since it can be detected in fetal liver, including cells of the pare...

Background SK Hep-1 cells (SK cells) derived from a patient with liver adenocarcinoma have been considered a human hepatoma cell line with mesenchymal origin characteristics, however, SK cells do not express liver genes and exhibit liver function, thus, we hypothesized whether mesenchymal cells might contribute to human liver primary cancers. Here,...

Combined hepatocellular-cholangiocarcinoma (cHCC-CC) accounts for <1% of all primary liver carcinomas (PLC). In this study, we evaluated the cases of cHCC-CC diagnosed in a major tertiary care hospital in New York. All PLC with HCC elements, diagnosed between 2008 and 2013, were retrospectively reviewed. cHCC-CC cases were identified and their asso...

A 62-year-old female presented with abdominal pain, weight loss of 20 kg in the prior 6 months, and a palpable mass in the right upper quadrant during physical exam. Standard liver tests, including screening for hepatitis B and C and alpha-fetoprotein were negative or within normal limits. Computerized tomography depicted a transmural gallbladder t...

believed that complementarityÀ Àsuch as wave–particle dualityÀ Àwas not limited to the quantum realm, but had correlates in the study of living things. Biological complementarity would indicate that no single technique or perspec-tive allows comprehensive viewing of all of a biological entity's complete qualities and behaviors; instead, complementa...