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C-kit receptor in the human vas deferens: distinction of mast cells, interstitial cells and interepithelial cells
in Reproduction
Authors: Roman Metzg
C-kit receptor in the human vas deferens: distinction of mast cells, interstitial cells and interepithelial cells
in Reproduction
Authors: Roman Metzger, Udo Rolle, Henning C Fiegel, Folker E Franke 1 , Karsten Muenstedt 1 and Holger Till
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DOI: https://doi.org/10.1530/REP-07-0346Page(s): 377â384Volume/Issue: Volume 135: Issue 3
Article Type: Research ArticleOnline Publication Date: Mar 2008Copyright: © 2008 Society for Reproduction and Fertility 2008
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Abstract
The molecular mechanisms underlying the regulation of vas deferens (VD) motility and semen emission are still poorly understood. Interstitial cells of Cajal (ICC), which harbour the c-kit receptor (CD117), provide the basis of coordinated gut motility. We investigated whether c-kit receptor-positive cells also exist in the normal human VD. Enzyme and fluorescence immunohistochemical techniques were applied on serial sections of human proximal, middle, and distal VD segments (n=49) employing 13 different monoclonal and polyclonal antibodies recognizing the c-kit receptor. The c-kit receptor was detected in either round- or spindle-shaped cells. On account of their antigenic profile, the round- and oval-shaped c-kit receptor-positive cells were identified as mast cells (MC) occurring in all layers of the VD except the epithelium. In contrast, two distinct populations of exclusively c-kit receptor-positive spindle-shaped cells were found within the lamina propria and, rarely, in the inner and outer smooth muscle layers, as well as within the epithelium. Different shaped c-kit receptor-positive MC and IC were present in all layers of the human VD. Our findings demonstrate the presence of different c-kit receptor-positive cells also in the human VD. Their rather ubiquitous distribution within the lamina propria and muscle layers suggests that IC and MC may modulate the neuromuscular transmission and the propagation of electrical signals in multiple systems involved in the draining of fluids. The importance of the c-kit receptor-positive interepithelial cells remains unclear.
Introduction
The interstitial cells of Cajal (ICC) are known to play an important role in the control of gut motility by providing electrical impulses for slow wave smooth muscle activity and neurotransmission (Huizinga et al. 1995). The ICC cell membrane harbours the c-kit receptor (CD117), which allows the identification of these cells by immunochemical and molecular methods (Lammie et al. 1994). ICC were found primarily close to the intestinal myenteric plexus, and also in the submucosal plexus and septa of the muscle layers. Lack or absence of c-kit immunoreactivity in the gut has been associated with gastrointestinal motility disorders (Yamataka et al. 1995, Streutker et al. 2003).
Recently, we have demonstrated the unique distribution of Cajal-like cells (CLC) in the normal upper urinary tract in humans and various animal species (Metzger et al. 2004, 2005). There is an ongoing discussion whether or not these CLC provide peristaltic activity in the upper urinary tract. A recent publication showed the ability of CLC to trigger contractions of the neighbouring smooth muscles of the ureterovesical junction in the mouse (Lang et al. 2007).
Similar to the ureter, the molecular mechanisms underlying the regulation of vas deferens (VD) motility are still poorly understood. The detection of cells representing a potential pacemaker system in the VD may improve our understanding of neurophysiological and pathological conditions of the male genitourinary tract.
Therefore, the present study analyses the cellular localization and distribution of c-kit receptor-positive cells in the human VD using a panel of monoclonal and polyclonal antibodies (pAb).
Results
All anti-c-kit receptor antibodies showed a uniform reaction pattern. The staining results were comparable using paraffin or frozen sections. Furthermore, no differences were found between cancer and autopsy cases. Special reference regions were used and the resulting staining density did not reveal specific differences between the used different mono- and polyclonal c-kit antibodies.
The c-kit receptor was detected in three different cell types. The first source occurred in spindle interstitial cells (IC) that demonstrate an oval nucleus and a bipolar cytomorphology with two thin, often wavy processes (Fig. 1). These cells were found frequently in the lamina propria and rarely along neurovascular septa and in between smooth muscle bundles (Figs 1 and 2). These cells do not form three-dimensional networks as confirmed by confocal microscopy. Using double-labelling immunofluorescence, the spindle-shaped cells did not stain with the control markers analysed (Table 1 and Fig. 2). The amount of c-kit-positive spindle-shaped cells increased continuously from the proximal VD to the ampulla of the VD (Fig. 3) in accordance with the density of S100 positive neurons and the thickening of the smooth muscle layer. The cell frequency of IC was significantly different in the segments analysed. A significant (P<0.001) increase in cell frequency was observed from the proximal VD (4.00±0.54 cells/high power field (hpf)) towards the ampulla (11.50±4.04 cells/hpf).
Figure 1ïżŒ
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Expression of the c-kit receptor in the vas deferens. C-kit receptor-positive interstitial cells (arrow head) between smooth muscle cells of the lamina muscularis (A) and in the lamina propria (B and C). Round-shaped, c-kit receptor-positive mast cells (arrows) in the neighbourhood of a c-kit receptor-positive interepithelial cell (arrow head) (D). The c-kit receptor-positive interepithelial cells attach the basal lamina and reach the luminal surface. (AâD) Anti-c-kit. Original magnification A, B and D Ă40, C Ă63, CSA.
Citation: REPRODUCTION135, 3; 10.1530/REP-07-0346
Figure 2ïżŒ
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Double-labelling immunofluorescence of c-kit receptor and controls in the vas deferens. C-kit receptor-positive cells occur in the epithelium (A), the lamina propria (B) and the muscularis propria (C and D). (A) C-kit receptor expression in interepithelial cells (arrow head) and in mast cells (arrow) of the lamina propria (A-1), which usually express both c-kit receptor and mast cell tryptase (A-2 and A-3). The blue line marks the position of the basal lamina of the epithelium. (B) C-kit receptor in a subepithelial spindle cell (arrow head) and a mast cell (B-1 and B-3). The blue line marks the position of the basal lamina of the epithelium. Some tryptase positive mast cells (arrow) do not express the c-kit receptor and demonstrate an elongated cytoplasm (B-2 and B-3). (C) C-kit receptor-positive spindle-shaped cell (arrow head) and mast cell (arrow) within the lamina muscularis. These spindle cells are negative for mast cell tryptase (C-2 and C-3). (D) C-kit receptor-positive spindle-shaped cell (arrow head) close to a neurovascular bundle (D-1 and D-3). The c-kit receptor-positive cells do not express CD34. The arrow marks CD34 positive endothelial cells (D-2 and D-3). A-1, B-1, C-1, D-1; anti-c-kit, Cy3 (red fluorescence). A-2, B-2 and C-2; anti-mast cell tryptase mAb AA1, Cy2 (green fluorescence). D-2; anti-CD34 mAb QBEnd/10, Cy2 (green fluorescence). A-3, B-3, C-3 and D-3; red and green fluorescence. Axiovert 200, original magnification A Ă20, B, C and D Ă40.
Citation: REPRODUCTION135, 3; 10.1530/REP-07-0346
Figure 3ïżŒ
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The figure shows the frequency (cells/hpf) of c-kit receptor-positive spindle-shaped cells in the lamina propria and muscularis propria. The cell frequency of interstitial cells was significantly different in the segments analysed. A significant (P<0.001) increase in cell frequency was observed from the proximal vas deferens (4.00±0.54 cells/hpf) towards the ampulla (11.50±4.04 cells/hpf).
Citation: REPRODUCTION135, 3; 10.1530/REP-07-0346
Table 1
Control antibodies.
CloneImmunogenConcentration(ÎŒg/ml)SourceQBEnd/10aCD342.0DianovaIC/70AaCD312.3DakoS-100aCow S-1000.2DakoBBS/NC/VI-H14aNSE4.3Dako2F11Neurofilament5.4DakoAA1aMast cell tryptase2.0DakoCC1aMast cell chymase1.0Serotec, DĂŒsseldorf, GermanyHHF35aα- and ÎČ-actin0.6Dako1A4aα-actin0.6DakoKP1aCD687.6DakoPG-M1aCD687.2DakoMR12/53b,cRabbit Ig1.0Dako
aReactive on microwave-pretreated formalin-fixed tissue section.
bUsed as negative control in APAAP technique.
cUsed as secondary antibody for antibodies raised in rabbits.
The second source of c-kit receptor-expressing cells was found in individual and vertically orientated cells within the epithelium. These cells have an oval nucleus, originated from the basal lamina and usually reach the lumen. The interepithelial cells (IEC) occurred more frequently in the proximal segment and only sporadically in the intermediate segment of the VD (Fig. 1). The ampulla showed a diffuse epithelial staining (Fig. 4). Using double-labelling IF, these IEC could not be attributed to the control markers analysed (Table 1).
Figure 4ïżŒ
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Double-labelling immunofluorescence of c-kit receptor and controls in mast cells and epithelial cells of the human vas deferens. Coexpression of the CD117 and mast cell tryptase in MC (A). Confocal microscopy shows that the cytoplasm marked by anti-mast cell tryptase (A-2 and A-3) in some mast cells is significantly smaller than marked by anti-c-kit receptor (A-1 and A-3). Note the perinuclear staining of anti-mast cell tryptase (A-2 and A-3) in contrast to staining of anti-c-kit receptor, which marks the cytoplasmatic border of long cytoplasmatic processes (A-1 and A-3). Most MC demonstrated either a round-shaped cytoplasm or usually plump cytoplasmatic processes (B-1 and B-3). These are often located at the interface of neurovascular bundles and smooth muscle cells (B-2 and B-3). Diffuse c-kit staining in epithelial cells of the ampulla (C-1 and C-3). A-1, B-1and C-1: anti-c-kit, Cy3 (red fluorescence). A-2: anti-mast cell tryptase mAb AA1, Cy2 (green fluorescence). B-2: anti-S100 pAb, Cy2 (green fluorescence). C-2: anti-smooth muscle actin mAb 1A4, Cy2 (green fluorescence). A-3, B-3 and C-3: red and green fluorescence. A: Zeiss Axioplan 2, LSM 510 Meta; B, C: Zeiss Axiovert 200, original magnification Ă40.
Citation: REPRODUCTION135, 3; 10.1530/REP-07-0346
The third source of c-kit-positive cells was identified as mast cells (MC), which showed the exclusive coexpression of both CD117 and MC tryptase/chymase. The cytomorphology of MC demonstrates a wide range of polymorphisms. Most MC possessed either a round-shaped cytoplasm or plump cytoplasmatic processes. Double-labelling analysis revealed that the cytoplasm of individual cells marked by anti-MC tryptase was sometimes smaller than marked by anti-c-kit (Fig. 3). MC were found in a varying amount throughout the entire wall of the VD, but usually not in the epithelium (Fig. 2). The amount of c-kit-positive MC was highest in the ampulla of the VD, followed by the proximal VD and intermediate segment, which were not different from each other (Fig. 5). A significant (P<0.001) higher cell frequency was observed in the ampulla of the VD (54.50±13.44 cells/hpf) compared with the proximal VD (22.50±13.92 cells/hpf). However, no statistically significant difference was seen between the proximal and intermediate VD.
Figure 5ïżŒ
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The figure shows the frequency (cells/hpf) of c-kit receptor-positive mast cells in the lamina propria and muscularis propria. A significant (P<0.001) higher cell frequency was observed in the ampulla of the vas deferens (54.50±13.44 cells/hpf) when compared with the proximal vas deferens (22.50±13.92 cells/hpf). However, no statistically significant difference was seen between the proximal and intermediate vas deferens.
Citation: REPRODUCTION135, 3; 10.1530/REP-07-0346
Coexpression studies clearly revealed that c-kit-positive IC are distinct from neural, muscular, endothelial and histiocytic structures. The CD117-positive round-shaped cells were uncovered as MC. However, the interepithelial CD117 positive cells could not be attributed to any other marker used.
Discussion
The present study demonstrates the complex morphology and distribution of the c-kit receptor (CD117) in particular cells of all layers and segments of the human VD, confirmed by the uniform reactivity of various anti-c-kit receptor antibodies. Whereas the majority of these cells were identified as intermingled MC, we found two distinct c-kit-positive cell types, negative for all other analysed cell markers.
These cells occurred either in the epithelium (IEC) or in the lamina propria as well as between the muscles layers (IC). Our findings in humans are supported by previously reported ultrastructural evidence for ICC-like IC in the monkey VD and immunohistochemical studies in the guinea pig (Leong & Singh 1990, Burton et al. 2000). These cells were also more densely distributed in the lamina propria than in the muscle layers.
The existence of CLC in the upper and lower urinary tract has been clearly shown before (Hashitani 2006, McHale et al. 2006, Lang et al. 2007). The present study revealed numerous IC that did not form a clear network. Since CLC in VD have a spindle shape but not âstag-hornâ appearance, these cells may be more likely resemble to intermuscular ICC in the gut, which play an important role in the neuromuscular transmission and the propagation of electrical signals (Huizinga et al. 1995, Liu et al. 2003, Ward & Sanders 2006).
Alternatively, IC may act as a mechanosensor since spontaneous contractions in VD are initiated by stretching or perfusion. This specific function has been assumed for ICC within the gastrointestinal tract. Previously uncharacterized non-neural stretch reflex has been demonstrated in gastric muscles, which provides physiological evidence for a mechanosensitive role of ICC in smooth muscle tissues (Won et al. 2005).
Modified smooth muscle cells may be capable of generating spontaneous electrical activity, which has been proven within the upper urinary tract (Brading & McCloskey 2005, Brading 2006).
Ureteral peristaltic activity begins with the origin of electrical activity at pacemaker sites. These sites are located in the proximal portion of the urinary collecting system. The âatypicalâ smooth muscle cells at these sites fire âpacemakerâ potentials at a frequency higher than the âdrivenâ action potentials recorded from typical smooth muscle cells. In contrast to typical smooth muscle cells, these atypical pacemaker cells have <40% of their cellular area occupied by contractile filaments and demonstrate a sparse immunoreactivity for α-smooth muscle actin. Expression of c-kit, a tyrosine kinase receptor, correlates with the onset of organized ureteral peristalsis in the embryo (Weiss et al. 2006).
VD smooth muscle cells generate spontaneous action potential and associated contractions in the guinea pig-cultured cell models (McLean et al. 1979). It remains unclear if these cells are variations of specialized ICC belonging to the autonomous neuromuscular system of the VD. However, these cells show a close resemblance to the recently described CLC of the ureter (Metzger et al. 2004, 2005).
The ubiquitous distribution of MC in the musculature and within the lamina propria of the human VD may hint to further functional properties.
There is clear evidence that MC may also contribute to smooth muscle activity and neural stimulation by releasing a variety of substances (Keith et al. 1995, Corvera et al. 1999, Hollenberg & Bunnett 1999, Reed et al. 2003, Vodenicharov et al. 2005). Histamines, prostaglandins and leukotrienes are potential paracrine signals in the communication pathways between MC and intrinsic neurons or smooth muscle cells of the VD.
Structural and functional relationships between i.m. ICC and MC have been documented within the gastrointestinal tract (Zarate et al. 2006). Ultrastructural analysis showed that i.m. ICC are frequently surrounded by MC with established membrane-to-membrane contacts. Furthermore, the release of cytoplasmatic vesicles directed to ICC was observed (Zarate et al. 2006).
The cytoplasmatic vesicles in MC exhibited characteristic morphological changes defined as piecemeal degranulation that is thought to be associated with vesicle-mediated long-lasting release of the vesicle content (Dvorak et al. 1994).
MC can synthesize different cytokines with proinflammatory and anti-inflammatory properties, modulating the function, survival and proliferation of other cells. Some of these mediators, such as histamine, heparin, tryptase, tumour necrosis factor and transforming growth factor, can induce proliferation and migration of fibroblasts (Metcalfe et al. 1997).
Human MC represent a major source of fibroblast growth factor and in turn fibroblasts are a major source of stem cell factor (SCF), the most important cytokine-regulating growth and function of MC and ICC (Huizinga et al. 1995, Linenberger et al. 1995).
Moreover, MC themselves are able to synthesize, contain and release SCF (Zhang et al. 1998, de Paulis et al. 1999). Recent studies indicate that membrane-bound SCF stimulates activation of the c-kit receptor more effectively than soluble SCF (Linenberger et al. 1995, Welker et al. 1999, Rich et al. 2003).
The seminal ducts serve several functions, especially, the transport of sperms from the testis to the urethra, sperm storage and post-testicular sperm maturation. Prior to ejaculation, semen undergoes a pulsatile transport from the storage in the epididymis through the VD to the prostatic urethra, called emission. So far, both processes are generally considered to function via sympathetic stimulation with supplementary parasympathetic involvement (Kolbeck & Steers 1992, 1993).
Blockage of the neural input leads to the elimination of peristaltic contractions but leaves slow rhythmic waves, indicating an independent intrinsic mechanism, which coordinates contraction in the absence of neural input. They appear, for example, when the denuded VD is stretched (Bruschini et al. 1977, Kolbeck & Steers 1992).
In our study the amount of c-kit receptor-positive cells of the lamina propria and muscularis was the lowest in the proximal portion and increased towards the ampulla of the VD. This coincided with an increase of neurons and smooth muscle cells, suggesting functional differences within a complex neuronal system of the VD in addition to the sympathetic and parasympathetic input.
The c-kit receptor-positive IEC have not previously been recognized and may have been an unnoticed cell population. One can only speculate about the possible functions IEC may harbour. These cells may own some receptor function for factors released by spermatozoa. Alternatively, IEC may also act as a mechanosensor since spontaneous contractions in VD are initiated by stretching or perfusion (Won et al. 2005). Or, IEC simply reflect an epithelial stem cell, reflecting the regeneration of the epithelium.
Based on our purely morphological findings, these conclusions are speculative and further investigations are required to conduct this discussion. However, a functional relation with the c-kit-positive urothelial cells is suggeste
Potential negative effects of anti-histamines on male reproductive function
in Reproduction Authors: Carolina Mondillo, et.al.
âThe potential negative impact of anti-histamines on male reproduction becomes even more dramatic if we consider that HA has also been associated with human sexual behavior and penile erection. What is more, although testicular mast cells are the major source of locally produced HA, recent studies have described HDC expression in macrophages, Leydig cells and germ cells, revealing the existence of multiple sources of HA within the testis. Undoubtedly, the more we learn about the testicular histaminergic system, the more opportunities there will be for rational design of drugs aimed at treating HA-related pathologies, with minimum or nule negative impact on fertility.â
Figure: Schematic representation of the adult human testis indicating potential sources of HA as well as HA-target cells. â spermatozoa, ⥠Sertoli cell, âą germ cells, ⣠peritubular cell, †Leydig cell, â„ mast cell/basophil, ⊠macrophage, ⧠fibroblast. HAS, Histamine (HA) source; Target for locally produced HA and/or histaminergic drugs.
Sensitization of pelvic nerve afferents and mast cell infiltration in the urinary bladder following chronic colonic irritation is mediated by neuropeptides
Elena E. Ustinova, et.al.
"Chronic pelvic pain (CPP) disorders such as irritable bowel syndrome (IBS), interstitial cystitis (IC), and chronic prostatitis (male CPP syndrome) affect both men and women and have a prevalence rate as high as 15% in both the United States and the United Kingdom (3, 6, 27, 30, 51).
In the right setting, CPP can develop following acute or chronic irritation of individual pelvic visceral organs, their associated striated sphincters, striated muscular structures of the pelvic floor, and/or striated and cutaneous components of the pelvic abdominal wall and/or perineum (14).
Because physiological activity of the colorectum and urinary bladder and their respective sensory input are a vital part of daily, conscious visceral pelvic activity (exclusive from other pelvic organs), it is not surprising that IBS and IC, analogous disorders of pelvic visceral pain and hypersensitivity, account for one-half of all cases of CPP."
Gentlemen, if youâre on high dose antihistamine
The role of mast cells in male infertility
Gerd Haidl,Yong-Gang Duan,Shu-Jian Chen,Frank-Michael Kohn,Hans-Christian Schuppe &Jean-Pierre Allam
"Increased numbers of mast cells (MCs) were described in the testes of males exhibiting infertility many years ago. Since beneficial effects of treatment with MC blockers on impaired male fertility were reported, more attention has been drawn on the role of MCs in the male reproductive tract.
The main interest is focused on testicular MCs, however MCs also occur in the epididymis and seminal fluid, which may be relevant for fertility as well. The increase in testicular MCs in close contact to the seminiferous tubules indicates a relationship between MC proliferation and a dysfunction of the bloodâtestis barrier.
Activated MCs not only coincide with fibrotic events, but also with elevated numbers of several types of immune cells in the testes of infertile men and may, therefore, be involved in the pathogenesis of testicular inflammatory processes as well.
Outside the testis, MCs have really been assigned a key role in chronic protatitis/chronic pelvic pain syndrome. The occurrence of MCs in the seminal plasma of fertile/infertile men and negative effects on sperm functions has not been clarified so far and require further investigation.
Optimistic reports on the beneficial effects of the treatment with MC blockers on disturbed male fertility also warrant further confirmation."
THE TREATMENT WITH TRANILAST, A MAST CELL BLOCKER, FOR IDIOPATHIC OLIGOZOOSPERMIA
H. HIBI, K. KATO, K. MITSUI et.all.
"A new approach for the treatment of male infertility focuses on the role of mast cell blockers, which inhibit the release of histamine and other vasoactive substances from mast cells.
The rationale of this approach is based on the observation of mastocytosis in the testis of infertile males reported by Maseki et al. [5].
Previously we reported the efficacy of oral administration of mast cell blocker for idiopathic severe oligozoospermia in a placebo-controlled prospective randomized study [10].
We examined whether a mast cell blocker, tranilast, improves fertility and/or semen parameters in severe idiopathic oligozoospermia."
On this beautiful afternoon I saw a bunch of kids, teens, and adults out playing basketball at a local church.
Unless you are taking them to the doctor, you should be keeping your kids at home with this virus starting to accelerate. More and more young people are getting infected and hospitalized.
Have you seen the fight over ventilators?
What kills is ARDS. Advanced Respiratory Distress Syndrome. This ainât the freaking flu. Itâs not chicken pox. Itâs like pneumonia from hell when youâve been huffing concrete dust into you lungs.
Your immune system is running at max and compromised by the virus. It attacks and the left over fluids surround the spaces in and around your lungs. You drown in you own immune fluids and lung tissue gets stiff as plastic and you canât breathe.
You die alone.
When the kid rolls in to the ER choking and canât get their breath, the first thing is to intubate to stick and airway down past your vocal cords and inflate a bladder to keep it there. Maybe the last time you talk with your kid.
The machine starts to breathe for them, but the fluid from their immune system, fighting the virus, is filling up the alveoli air sacks and the interstitial spaces around it.
It becomes fibrotic, like putty and your available air volume drops by half. They sedate you and paralyze you with drugs so that they can adjust the machine to exhale at lower pressures that itâs pumping in to keep the airways from collapsing. The flip them on their belly to try and create more volume.
Your kidâs brain is exploding because it thinks theyâre drowning. They want to breathe, to live, they want their Momma, but they are alone.
Maybe in 14 to 21 days, if they can wean them off, they can breathe on their own again. But the immune system response to the virus has damaged the tissue cell structure of the lungs and heart and kidney and theyâll never play ball again.
Oh and you canât be there with them and hold their hand, because theyâre infectious and you might be too. Not allowed in the ICU with them. Alone with the machine, in and out, beep beep beepâŠsedated, paralyzed and drowning because you let them go play with their friends.
Welcome to Pandemic 101. And this is coming back after this round, late summer, early winter, sometime. Weâre just pushing it down the road, hoping for a vaccine in 12 to 18 months. Hopefully mutate for the good and not the bad.
So yep, I understand, hanging with the homies, basketball, in your face, sweating, pushing, yelling, spitting is important.
So if each of those 20 people each contact and maybe infect 15 others in a week, 21 days from now odds are at least one in 300 of them will be in an ICU alone with a ventilator hose stuck down their airway, speechless, drowning, choking, and alone.
Keep your children home, you too. I donât want them to get sick or die, and I donât want them to kill or sicken someone I know or love.
Thanks to Kim
Would love to see the rest of this presentation
Flattening the Curve for over 10 years âŠ
Bum bum bum bumâŠWeâre Pinky, Pinky and the Brain, Brain, Brain, BrainâŠ
From my Grandblessings
Omalizumab and Mast Cell Disorders: Are We There Yet? Catherine R. Weiler, MD, PhD Rochester, Minn
https://www.jaci-inpractice.org/article/S2213-2198(19)30434-9/pdf
Now that the viral spike has been visualized and 3 d modeled with cryoEM here you go, #hope
Paper preprint: The first-in-class peptide binder to the SARS-CoV-2 spike protein
#youronlyasgoodasthereachofyourtools
Picture of the day: Since the beginning of the pandemic and the fact that it affects the elderly so lethally, an African proverb has kept in my mind:
âWhen an old person dies, a library burns to the ground.â
Yesterday, in his address to his nation, Ghana President, Nana Akufo-Addo said:
âWe know how to bring the economy back to life. What we do not know is how to bring people back to lifeâ
LIMA pennant, âLimaâ, also called the âYellow Jackâ when flown in harbor, now means âship is under quarantineâ.
Do I fly one for 1 for quarantine and 2 for isolation like tropical storm warning vs hurricane? Why donât they tell us this important stuff.
Where is the Corona Cone of Uncertainty??
And most important, where is Jim Cantore??
#Floridavirusquarantineproblems #yellowjackisback
Systemic Masto
God Bless our Nurses and RTs. Clinical education from the front lines.
The novel coronavirus is mutating, as viruses do, and eight strains are now making the rounds globally, medical experts say.
The good news is that the mutations are not more lethal, said Trevor Bedford, whose website,( https://nextstrain.org ), is tracking the virusâs genome from samples provided to him from throughout the world.The strains emerging are only slightly tweaked, with no variations in lethality, experts said.
"The observed rate of mutation (about two mutations per month) is completely normal for a virus,â Bedford wrote on Twitter. âFlu and the common cold have similar mutation rates. Even a bit faster for flu.â
READ MORE: https://nextstrain.org/#philosophy
Yup, you bet your ass, Harvard and the Canadianâs level 4 were duped too.
Coeliac Disease and Mast Cells
July 2019 International Journal of Molecular Sciences 20(14):3400 DOI:
10.3390/ijms20143400