Persius/hicric huggingface dataset:
Intraglomerular mesangial cell

# Overview
Intraglomerular mesangial cells are specialized pericytes located among the glomerular capillaries within a renal corpuscle.
There are three primary functions of intraglomerular mesangial cells: filtration, structural support, and phagocytosis.

## Filtration and structure
Glomerular capillaries consist of endothelial cells with large fenestrations, and are therefore very permeable ("leaky") for most solutes in blood plasma.
They provide structural support for and regulate blood flow of the glomerular capillaries by their contractile activity.
They are also major contributors to the extracellular matrix which contains fibronectin, type IV collagen, perlecan, and laminin.

## Phagocytosis
Mesangial cells also phagocytose glomerular basal lamina components and immunoglobulins.
Itraconazole contraindications
CONTRAINDICATIONS
Congestive Heart Failure
SPORANOX (itraconazole) Capsules should not be administered for the treatment of onychomycosis in patients with evidence of ventricular dysfunction such as congestive heart failure (CHF) or a history of CHF. (See WARNINGS, PRECAUTIONS: Drug Interactions-Calcium Channel Blockers, ADVERSE REACTIONS: Post-marketing Experience, and CLINICAL PHARMACOLOGY: Special Populations.)
Drug Interactions
Concomitant administration of SPORANOX (itraconazole) Capsules or Oral Solution and certain drugs metabolized by the cytochrome P450 3A4 isoenzyme system (CYP3A4) may result in increased plasma concentrations of those drugs, leading to potentially serious and/or life-threatening adverse events. Cisapride, oral midazolam, nisoldipine, felodipine, pimozide, quinidine, dofetilide, triazolam, methadone and levacetylmethadol (levomethadyl) are contraindicated with SPORANOX. HMG CoA-reductase inhibitors metabolized by CYP3A4, such as lovastatin and simvastatin, are also contraindicated with SPORANOX. Ergot alkaloids metabolized by CYP3A4 such as dihydroergotamine, ergometrine (ergonovine), ergotamine and methylergometrine (methylergonovine) are contraindicated with SPORANOX. (See BOX WARNING, and PRECAUTIONS: Drug Interactions.)
SPORANOX should not be administered for the treatment of onychomycosis to pregnant patients or to women contemplating pregnancy.
SPORANOX is contraindicated for patients who have shown hypersensitivity to itraconazole or its excipients. There is no information regarding cross-hypersensitivity between itraconazole and other azole antifungal agents. Caution should be used when prescribing SPORANOX to patients with hypersensitivity to other azoles.
Kaptin (actin binding protein)
Kaptin is a protein that in humans is encoded by the KPTN gene.

# Model organisms
Model organisms have been used in the study of KPTN function. A conditional knockout mouse line, called Kptntm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program  a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty two tests were carried out on mutant mice and six significant abnormalities were observed. Homozygous mutant mice had hyperalbuminemia, decreased mature B cell numbers and  increased susceptibility to bacterial infection. Female mice also had increased body weight, body fat and impaired glucose tolerance.
KiSS1-derived peptide receptor
The KiSS1-derived peptide receptor (also known as GPR54 or the Kisspeptin receptor) is a G protein-coupled receptor which binds the peptide hormone kisspeptin (metastin). Kisspeptin is encoded by the metastasis suppressor gene KISS1, which is expressed in a variety of endocrine and gonadal tissues. Activation of the kisspeptin receptor is linked to the phospholipase C and inositol trisphosphate second messenger cascades inside the cell.

# Function
Kisspeptin is involved in the regulation of endocrine function and the onset of puberty, with activation of the kisspeptin receptor triggering release of gonadotropin-releasing hormone (GnRH), and release of kisspeptin itself being inhibited by oestradiol but enhanced by GnRH. Reductions in kisspeptin levels with age may conversely be one of the reasons behind age-related declines in levels of other endocrine hormones such as luteinizing hormone.

# Ligands
No non-peptide ligands for this receptor have yet been discovered, but as of 2009 both selective agonist and antagonist peptides are known.

## Agonists
- Kisspeptin
- Kisspeptin-10 (112-121 C-terminal fragment)

## Antagonists
- Kisspeptin-10 analogues modified with amino substitutions
Lactobacillus sanfranciscensis
Lactobacillus sanfranciscensis (formerly L. sanfrancisco) is a species of lactic acid bacteria that helps give sourdough bread its characteristic taste.
Sourdough starters are leavened by a mixture of yeast and lactobacilli in a ratio of about 1:100. The yeast is most commonly Candida milleri. This yeast cannot metabolize the maltose found in the dough, while the Lactobacillus needs maltose. They therefore act without conflict for substrate, with the Lactobacillus utilizing maltose and the yeast utilizing the other sugars, including the glucose produced by the Lactobacillus. The lactobacilli produces an antibiotic cycloheximide which kills many organisms (but not the Candida), and the Candida tolerates the acetic acid produced by the lactobacilli.
For commercial use, specific strains of the L. sanfranciscensis are grown on defined media, freeze-dried, and shipped to bakeries worldwide.
Left atrial enlargement causes

# Overview
In the general population, obesity appears to be the most important risk factor for left atrial enlargement. Persistent atrial fibrillation results in retention of blood in the left atrium secondary to inadequate pumping of blood by the atrium into the left ventricle. Similar pathophysiologic process occurs in mitral stenosis resulting in subsequent left atrial enlargement. Aortic stenosis, mitral regurgitation, aortic insufficiency and other causes of left ventricular heart failure causes an increase in back pressure within the atrium resulting in subsequent left atrial enlargement.

# Differential Diagnosis of Causes of Left Atrial Enlargement

## By Organ System

## In Alphabetical Order
- Ankylosing spondylitis
- Aortic regurgitation
- Aortic stenosis
- Atrial fibrillation
- Atrial septal defect
- Cardiac amyloidosis
- Chronic alcoholism
- Coarctation of the aorta
- Congestive heart failure
- Coronary artery disease
- Emphysema
- Hypertrophic cardiomyopathy
- Hypercholesterolemia accelerates the stenotic process of the valves via calcification
- Hypoplasia of mitral valve annulus which is a part of the spectrum of hypoplastic left heart syndrome
- Infective endocarditis
- Ischemic mitral regurgitation
- Left atrial myxoma
- Left bundle branch block
- Mitral regurgitation
- Mitral stenosis
- Mitral valve annular calcification
- Mitral valve commissural fusion
- Mitral valve prolapse
- Obesity
- Papillary muscle rupture
- Parachute mitral valve
- Pneumonia
- Prosthetic mitral valve stenosis
- Rheumatic heart disease
- Supra-valve mitral membrane
- Systemic hypertension
- Thickened chordae tendinae
- Thrombus (ball valve thrombus) in left atrium
Long-term video-EEG monitoring
Long-term video-EEG monitoring, also known as video telemetry, is a diagnostic technique used in certain patients with epilepsy or seizures.  It involves the inpatient hospitalization of the patient for a period of time, typically days to weeks, during which they are continuously monitored and recorded with a video camera and an electroencephalograph.
The recording is periodically monitored and analyzed by a neurologist, typically one trained in clinical neurophysiology; the neurologist determines when the monitoring is finished and issues the final report.
The purposes of long-term video-EEG monitoring include:
- discovering where in the brain a given person's seizures begin
- distinguishing epileptic seizures from psychogenic non-epileptic seizures
- evaluating a person who is a candidate for surgery to treat epilepsy
Lopinavir ritonavir overdosage

# Overdosage
Overdoses with KALETRA oral solution have been reported. One of these reports described fatal cardiogenic shock in a 2.1 kg infant who received a single dose of 6.5 mL of KALETRA oral solution (520 mg lopinavir, approximately 10-fold above the recommended lopinavir dose) nine days prior. The following events have been reported in association with unintended overdoses in preterm neonates: complete AV block, cardiomyopathy, lactic acidosis, and acute renal failure . Healthcare professionals should be aware that KALETRA oral solution is highly concentrated and therefore, should pay special attention to accurate calculation of the dose of KALETRA, transcription of the medication order, dispensing information and dosing instructions to minimize the risk for medication errors and overdose. This is especially important for infants and young children.
KALETRA oral solution contains 42.4% alcohol (v/v) and 15.3% propylene glycol (w/v). Ingestion of the product over the recommended dose by an infant or a young child could result in significant toxicity and could potentially be lethal.
Human experience of acute overdosage with KALETRA is limited. Treatment of overdose with KALETRA should consist of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient. There is no specific antidote for overdose with KALETRA. If indicated, elimination of unabsorbed drug should be achieved by gastric lavage. Administration of activated charcoal may also be used to aid in removal of unabsorbed drug. Since lopinavir is highly protein bound, dialysis is unlikely to be beneficial in significant removal of the drug. However, dialysis can remove both alcohol and propylene glycol in the case of overdose with KALETRA oral solution.
Luliconazole adverse reactions

# Adverse Reactions

## Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug, and may not reflect the rates observed in practice.
In three Phase 3 clinical trials, 616 subjects were exposed to LUZU Cream, 1%: 305 with interdigital tinea pedis and 311 subjects with tinea cruris. Subjects with interdigital tinea pedis or tinea cruris applied LUZU Cream, 1% or vehicle cream once daily for 14 days or 7 days, respectively, to affected and adjacent areas. During clinical trials with LUZU Cream, 1%, the most common adverse reactions were application site reactions which occurred in less than 1% of subjects in both the LUZU and vehicle arms. Most adverse reactions were mild in severity.

## Post-Marketing Experience
The following adverse reactions have been identified during postmarketing use of luliconazole cream, 1%: contact dermatitis and cellulitis. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Lymphocyte cytosolic protein 2
Lymphocyte cytosolic protein 2 (SH2 domain containing leukocyte protein of 76kDa), also known as LCP2 or SLP-76, is a gene that encodes a signal-transducing adaptor protein.

# Structure
No full structure for SLP-76 has been solved. The PDB file 1H3H depicts the SH3 domain of GRAP2 in complex with an RSTK-containing peptide representing residues 226-235 of SLP-76.

# Function
SLP-76 was originally identified as a substrate of the ZAP-70 protein tyrosine kinase following T cell receptor (TCR) ligation in the leukemic T cell line Jurkat. The SLP-76 locus has been localized to human chromosome 5q33 and the gene structure has been partially characterized in mice. The human and murine cDNAs both encode 533 amino acid proteins that are 72% identical and composed of three modular domains. The NH2-terminus contains an acidic region that includes a PEST domain and several tyrosine residues that are phosphorylated following TCR ligation. SLP-76 also contains a central proline-rich domain and a COOH-terminal SH2 domain. A number of additional proteins have been identified that associate with SLP-76 both constitutively and inducibly following receptor ligation, supporting the notion that SLP-76 functions as an adaptor or scaffold protein. Studies using SLP-76-deficient T cell lines or mice have provided strong evidence that SLP-76 plays a positive role in promoting T cell development and activation as well as mast cell and platelet function. SLP-76 might serve as an integration point for signals by activating NK cell receptors. In NK cells, SLP-76 can be phosphorylated by SYK or ZAP70 following ligation of activating recptors.

# Interactions
Lymphocyte cytosolic protein 2 has been shown to interact with:
- Cbl gene,
- GRAP2,
- Grb2,
- ITK
- LYN,
- NCK1,
- PIK3R1,
- PLCG1,
- PTPN6,
- SHB,  and
- VAV1.
Macrophage-activation syndrome
Synonyms and keywords: MAS

# Overview
Macrophage-activation syndrome (MAS) is a severe, potentially life-threatening, complication of several chronic rheumatic diseases of childhood. It occurs most commonly with systemic-onset juvenile idiopathic arthritis (SoJIA), which is also known as Still's disease. In addition, MAS has been described in association with systemic lupus erythematosus (SLE), Kawasaki disease, and adult-onset Still's disease. It is thought to be closely related and pathophysiologically very similar to reactive (secondary) hemophagocytic lymphohistiocytosis (HLH). The incidence of MAS is unknown as there is a wide spectrum of clinical manifestations, and episodes may remain unrecognized.

# Pathophysiology
In many cases a trigger is identified, often a viral infection, or a medication. There is uncontrolled activation and proliferation of macrophages, and T lymphocytes, with a marked increase in circulating cytokines, such as IFN-gamma, and GM-CSF. The underlying causative event is unclear, and is the subject of ongoing research. In many cases of MAS, a decreased natural killer cell (NK-cell) function is found.

# Causes

## Drug side effect
- Canakinumab

# Diagnosis
The hallmark clinical and laboratory features include high fever, hepatosplenomegaly, lymphadenopathy, pancytopenia, liver dysfunction, disseminated intravascular coagulation, hypofibrinogenemia, hyperferritinemia, and hypertriglyceridemia. Despite marked systemic inflammation, the erythrocyte sedimentation rate (ESR) is paradoxically depressed, caused by low fibrinogen levels. The low ESR helps to distinguish the disorder from a flare of the underlying rheumatic disorder, in which case the ESR is usually elevated. A bone marrow biopsy or aspirate usually shows hemophagocytosis.
The diagnosis relies on the findings outlined above. In addition, other specific markers of macrophage activation (e.g. soluble CD63), and lymphocyte activation (e.g. soluble IL-2 receptor) can be helpful. NK cell function analysis may show depressed NK function, or, flow cytometry may show a depressed NK cell population.

# Treatment
The best treatment for MAS has not been firmly established. Most commonly used treatments include high-dose glucocorticoids, and cyclosporine. In refractory cases treatment regimens are used similar to that in HLH.
Mafenide clinical pharmacology

# Clinical Pharmacology

## Mechanism of Action
The mechanism of action of Mafenide is not known, but is different from that of the sulfonamides. Mafenide is not antagonized by pABA, serum, pus or tissue exudates, and there is no correlation between bacterial sensitivities to mafenide and to the sulfonamides. Its activity is not altered by changes in the acidity of the environment. The osmolality of the 5% topical solution is approximately 340 mOsm/kg.

## Absorption and Metabolism
Applied topically, Mafenide Acetate diffuses through devascularized areas. Approximately 80% of a Mafenide Acetate dose is delivered to burned tissue over four hours following topical application of the 5% solution. Following application of Mafenide Acetate cream and solution, peak Mafenide concentrations in human burned skin tissue occur at two and four hours, respectively. Peak tissue concentrations are similar following administration of the solution or cream. Once absorbed, Mafenide is rapidly converted to an inactive metabolite (p-carboxybenzenesulfonamide) which is cleared through the kidneys. Clinical studies have shown that when applied topically to burns as an 11.2% Mafenide Acetate cream, blood levels of the parent drug peaked at 2 hours following application, ranging from 26 to 197 g/mL for single doses of 14 to 77 g of Mafenide Acetate. Metabolite levels peaked at 3 hours, ranging from 10 to 340 g/mL. Twenty-four hours after application, combined parent and metabolite blood levels had fallen to pretreatment levels.

## Antimicrobial Activity
Mafenide Acetate exerts broad bacteriostatic action against many gram-negative and gram-positive organisms, including Pseudomonas aeruginosa and certain strains of anaerobes.

## In Vitro Cytotoxicity
Data from in vitro studies on cell culture suggests that Mafenide Acetate may have a deleterious effect on human keratinocytes. The clinical significance of this information is unknown.
Matilda International Hospital
Matilda Hospital was built as a result of the last will and testament of Granville Sharp, the husband of Matilda.
Originally from the UK, the couple travelled a long way, encountering many adventures (including shipwreck) along their way, before arriving in Hong Kong.
The hospital admitted its first patients in 1907, at that time providing free care to mainly expatriates.  The original building, which is still in use today, is outstandingly beautiful, as is the hospital's location on "the Peak" on Hong Kong island.
In the past it was known as the War Memorial Hospital, but nowadays, it has been renamed Matilda International Hospital, and is a not-for-profit hospital serving all the people of Hong Kong and the wider region.  It provides four core services: maternity, surgical, health assessment and health services.
A new clinic was opened in the Central area of Hong Kong to mark the hospital's centenary celebration in 2007.
Matilda International Hospital maintains very high clinical, governance and educational standards, and is surveyed and accredited bi-annually by the Trent Accreditation Scheme of the United Kingdom, a major international healthcare accreditation group.

# Trivia
Scenes in the Oscar-winning movie, "Love is a Many-Splendored Thing", were filmed at the Matilda hospital.
Metipranolol adverse reactions

# Adverse Reactions
In clinical trials, the use of metipranolol ophthalmic solution has been associated with transient local discomfort.
Other ocular adverse reactions, such as abnormal vision, blepharitis, blurred vision, browache, conjunctivitis, edema, eyelid dermatitis, photophobia, tearing, and uveitis have been reported in small numbers of patients.
Other systemic adverse reactions, such as allergic reaction, angina, anxiety, arthritis, asthenia, atrial fibrillation, bradycardia, bronchitis, coughing, depression, dizziness, dyspnea, epistaxis, headache, hypertension, myalgia, myocardial infarct, nausea, nervousness, palpitation, rash, rhinitis, and somnolence have also been reported in small numbers of patients.
Metipranolol drug interactions

# Drug Interactions
Metipranolol ophthalmic solution should be used with caution in patients who are receiving a beta-adrenergic blocking agent orally, because of the potential for additive effects on systemic beta-blockade.
Close observation of the patient is recommended when a beta-blocker is administered to patients receiving catecholamine-depleting drugs such as reserpine, because of possible additive effects and the production of hypotension and/or bradycardia.
Caution should be used in the coadministration of beta-adrenergic receptor blocking agents, such as metipranolol, and oral or intravenous calcium channel antagonists, because of possible precipitation of left ventricular failure, and hypotension. In patients with impaired cardiac function, who are receiving calcium channel antagonists, coadministration should be avoided.
The concomitant use of beta-adrenergic receptor blocking agents with digitalis and calcium channel antagonists may have additive effects, prolonging atrioventricular conduction time.
Caution should be used in patients using concomitant adrenergic psychotropic drugs.
Ocular: In patients with angle-closure glaucoma, the immediate treatment objective is to re-open the angle by constriction of the pupil with a miotic agent. Metipranolol ophthalmic solution has little or no effect on the pupil, therefore, when it is used to reduce intraocular pressure in angle-closure glaucoma, it should be used only with concomitant administration of a miotic agent.
Minimum alveolar concentration
Minimum alveolar concentration or MAC is a concept used to compare the strengths of anaesthetic vapours; in simple terms, it is defined as the concentration of the vapour in the lungs that is needed to prevent movement (motor response) in 50% of subjects in response to surgical (pain) stimulus. Thus, it is actually a median value; the use of minimum would appear to be descended from the original paper in which the concept appeared, although the term there was minimal alveolar concentration. If MAC is 1.0, then 1.3 MAC would block response in 99% of subjects.
Other uses of MAC include MAC-BAR (1.7-2.0 MAC), which is the concentration required to block autonomic reflexes to nociceptive stimuli, and MAC-awake (0.3-0.5 MAC), the concentration required to block voluntary reflexes and control perceptive awareness.

# Formal definition
The MAC is the concentration of the vapour (measured as a percentage at 1 atmosphere, i.e the partial pressure) that prevents the reaction to a standard surgical stimulus (traditionally a set depth and width of skin incisions) in 50% of subjects. This measurement is done at steady state (assuming a constant alveolar concentration for 15 minutes), under the assumption that this allows for an equilibration between the gasses in the alveoli, the blood and the brain.

# Meyer-Overton hypothesis
The MAC of a volatile substance is inversely proportional to its lipid solubility (oil:gas coefficient) , in most cases. This is the Meyer-Overton hypothesis. MAC is inversely related to potency i.e. high mac equals low potency.
The hypothesis correlates lipid solubility of an anaesthetic agent with potency (1/MAC) and suggests that onset of anaesthesia occurs when sufficient molecules of the anaesthetic agent have dissolved in the cell's lipid membranes, resulting in anaesthesia. Exceptions to the Meyer-Overton hypothesis can result from:
- convulsant property of an agent
- specific receptor (various agents may exhibit an additional effect through specific receptors)
- co-administration of Alpha2 agonists (dexmedetomidine) and/or opioid receptor agonists (morphine/fentanyl) can decrease the MAC
- Mullin's critical volume hypothesis
- positive modulation of GABA at GABAA receptors by barbiturates or benzodiazepines