"Liking" and "wanting" of sweet and oily food stimuli as affected by high-fat diet-induced obesity, weight loss, leptin, and genetic predisposition

Cross-sectional studies in both humans and animals have demonstrated associations between obesity and altered reward functions at the behavioral and neural level, but it is unclear whether these alterations are cause or consequence of the obese state. Reward behaviors were quantified in male, outbred Sprague-Dawley (SD) and selected line obesity-prone (OP) and obesity-resistant (OR) rats after induction of obesity by high-fat diet feeding and after subsequent loss of excess body weight by chronic calorie restriction. As measured by the brief access lick and taste-reactivity paradigms, both obese SD and OP rats "liked" low concentrations of sucrose and corn oil less, but "liked" the highest concentrations more, compared with lean rats, and this effect was fully reversed by weight loss in SD rats. Acute food deprivation was unable to change decreased responsiveness to low concentrations but eliminated increased responsiveness to high concentrations in obese SD rats, and leptin administration in weight-reduced SD rats shifted concentration-response curves toward that seen in the obese state in the brief access lick test. "Wanting" and reinforcement learning as assessed in the incentive runway and progressive ratio lever-pressing paradigms was paradoxically decreased in both obese (compared with lean SD rats) and OP (compared with OR rats). Thus, reversible, obesity-associated, reduced "liking" and "wanting" of low-calorie foods in SD rats suggest a role for secondary effects of the obese state on reward functions, while similar differences between select lines of OP and OR rats before induction of obesity indicate a genetic component.     

“一枝好”育发液促进毛发生长及机制探讨

目的:考察利用新疆维吾尔族传统药物研制成的"一枝好"育发液促进毛发生长的效果,并探讨其可能的作用机制。方法:采用硫化钠溶液建立昆明小鼠化学性脱发实验模型,将30只昆明小鼠随机分为实验组、阳性对照组(章光101育发剂)、空白对照组,以毛发评分、毛长、毛重以及毛囊数为指标,考察小鼠新生毛发生长情况。对脱毛后21天的脱毛区皮肤毛长、毛重、毛囊数进行测量和统计分析。并利用MTT法初步探讨"一枝好"育发液对人脐静脉血管内皮细胞(HUVEC)增殖的影响。结果:实验组脱毛区体毛生长评分及毛长,与空白对照组差异显著,并且略高于阳性对照组。对小鼠毛重与毛囊数的统计结果显示,与空白对照组和阳性对照组相比,实验组均有显著性差异(P0.01,P0.001)。"一枝好"育发液能够促进人脐静脉血管内皮细胞(HUVEC)增殖。结论:利用新疆维吾尔族传统药物研制成的"一枝好"育发液,能够显著促进小鼠毛发生长,初步推断其作用机制与促进毛囊生长和促进血管内皮细胞增殖有关。     

The effects of different exercise modes for preventing endothelial dysfunction of arteries and bone loss in ovariectomized rats

[Purpose]

Several epidemiological studies have demonstrated that there are positive correlations between vascular disorders and bone loss in postmenopausal women. The aim of the present study was to examine the effect of different types of exercise (e.g., climbing and swimming) for preventing endothelial dysfunction of arteries and bone loss in ovariectomized rats.

[Methods]

Twenty Sprague-Dawley female rats were randomly divided into three groups: ovariectomy (OVX) plus treatment with vitamin D₃ and nicotine (VDN) (control rats [Con], n = 7), which is an animal model for endothelial dysfunction and bone loss; voluntary climbing resistance exercise with OVX plus VDN (climbing rats [Clim], n = 6), and swimming exercise with OVX plus VDN (swimming rats [Swim], n = 7). The period of exercise training was 8 weeks.

[Results]

The endothelin-1 (ET-1) protein levels were significantly lower in the Clim and Swim groups than in the Con. The endothelial nitric oxide synthase protein levels were significantly higher in the Swim group than in the Con, but they did not differ between the Clim and Con groups. The cortical bone mineral density in the tibia and breaking energy of the femur were significantly higher in the Clim group than in the Con, but this positive effect was not seen in the Swim group.

[Conclusion]

Voluntary climbing exercise decreased arterial ET-1 protein levels and prevented bone loss in a postmenopause-model rat combining OVX and VDN. Conversely, swimming suppressed endothelial dysfunction of the arteries but did not prevent bone loss. Thus, the type of exercise should be cautiously chosen for enhancing vascular function and bone status, especially in females after menopause.     

Vasoregression Linked to Neuronal Damage in the Rat with Defect of Polycystin-2

Background

Neuronal damage is correlated with vascular dysfunction in the diseased retina, but the underlying mechanisms remain controversial because of the lack of suitable models in which vasoregression related to neuronal damage initiates in the mature retinal vasculature. The aim of this study was to assess the temporal link between neuronal damage and vascular patency in a transgenic rat (TGR) with overexpression of a mutant cilia gene polycystin-2.

Methods

Vasoregression, neuroglial changes and expression of neurotrophic factors were assessed in TGR and control rats in a time course. Determination of neuronal changes was performed by quantitative morphometry of paraffin-embedded vertical sections. Vascular cell composition and patency were assessed by quantitative retinal morphometry of digest preparations. Glial activation was assessed by western blot and immunofluorescence. Expression of neurotrophic factors was detected by quantitative PCR.

Findings

At one month, number and thickness of the outer nuclear cell layers (ONL) in TGR rats were reduced by 31% (p<0.001) and 17% (p<0.05), respectively, compared to age-matched control rats. Furthermore, the reduction progressed from 1 to 7 months in TGR rats. Apoptosis was selectively detected in the photoreceptor in the ONL, starting after one month. Nevertheless, TGR and control rats showed normal responses in electroretinogram at one month. From the second month onwards, TGR retinas had significantly increased acellular capillaries (p<0.001), and a reduction of endothelial cells (p<0.01) and pericytes (p<0.01). Upregulation of GFAP was first detected in TGR retinas after 1 month in glial cells, in parallel with an increase of FGF2 (fourfold) and CNTF (60 %), followed by upregulation of NGF (40 %) at 3 months.

Interpretation

Our data suggest that TGR is an appropriate animal model for vasoregression related to neuronal damage. Similarities to experimental diabetic retinopathy render this model suitable to understand general mechanisms of maturity-onset vasoregression.     

Reconstruction of rat femoral veins with microvascular prostheses

Synthetic conduits have not been suitable for microvascular reconstruction owing primarily to their high thrombogenicity. Vein replacements are the most vulnerable to thrombosis because of their low shear rates and low pressure. Experimental replacement of microvenous segments with prosthetic segments has shown little success. Recent technological advances in biomaterials and control of thrombogenesis provide the potential for success in the development of venous prostheses. The purpose of this study was to assess the use of nonbiodegradable composite polyurethane microvascular prostheses for reconstruction of rat femoral veins. Rat femoral venous defects of 10 mm were reconstructed with autogenous vein (n = 12), unprocessed plain polyurethane (n = 5), and nonbiodegradable composite polyurethane (n = 31). Patency was evaluated by direct observation and proximal venous milking tests. The patency rate of composite grafts was not significantly different from that of isotopic vein (p = 0.5, Fisher's exact test), and both had higher patency than unprocessed polyurethane (p less than 0.01). Composite grafts were examined sequentially using light and scanning electron microscopy. Grafts were fully endothelialized between the first and third months. The neointimal, neomedial, and neoadventitial layers could be seen more distinctly over time. New opportunities in reconstructive microsurgery may be opened by microvascular prostheses that are complaint and thromboresistant.     

The laser-assisted end-to-side microvascular anastomosis

A simple method of performing the laser-assisted end-to-side microvascular anastomosis was devised. This technique was tested on 150 Sprague-Dawley rats in two separate series of experiments. In the first, end-to-side anastomoses were performed on the iliac artery under the normal tension due to the elastic recoil of severed vessels. Four stay sutures were placed 90 degrees apart, and the intervals were "spot welded" with a low-wattage CO2 microsurgical laser unit. The patency rate (96 percent) was equivalent to that found in a control group utilizing the conventional all-suture method (92 percent), but there was a significantly higher aneurysm rate (44 versus 11 percent). In a second model, an arterial bypass with very low anastomotic tension was performed around an obstruction created in the carotid artery. This model resulted in turbulent flow but low anastomotic tension. Here the laser-anastomosis patency rate was 98 percent, versus 42 percent for the conventional all-suture method. The placement of fewer sutures in association with turbulent flow in this model may account for the improved patency rate. The avoidance of excessive tension at the anastomotic site reduced the incidence of aneurysms to a negligible level.     

Protective effects of coenzyme Q10 on ischemia-induced reperfusion injury in ischemic limb models.

We examined simple cold preservation of rat limbs in Euro-Collins' solution to elucidate the protective effect of coenzyme Q10 (CoQ10) on the ischemia-induced reperfusion injury in an ischemic extremity replant model. A total of 126 Lewis rat limb replants were performed. Limbs were amputated from donor rats and preserved at 4 degrees C in Euro-Collins' solution and were orthotopically grafted to isogeneic rats by microsurgical technique. In the experimental groups (n = 42), coenzyme Q10 (10 mg/kg) was injected intraperitoneally into the recipients about 1 hour before reperfusion. In the control groups (n = 84), the same dose of solvent was given by the same route. We evaluated vascular patency of anastomoses by direct observation or microangiogram and performed histologic examinations 7 days after replantation. In the control groups, the ischemic limit was 96 hours. Ischemic limbs treated with coenzyme Q10 showed a statistically significant (p < 0.05) improvement in vascular patency after 72 and 96 hours of ischemia. Histologically, bone viability with osteoblastic activity was maintained in coenzyme Q10-treated animals of the 72-hour ischemic group. We conclude that the protective effect of coenzyme Q10 on reperfusion injury is suggested in this replant model.     

Semiquantitative histochemical investigation of lysosomal enzyme activities in the aortic endothelial cells of rats with renal hypertension

To obtain information about changes in lysosomal enzyme activities in the aortic endothelial cells in arterial hypertension, semi-quantitative histochemical investigations of acid phosphatase (Ac-Pase) and N-acetyl-beta-glucosaminidase (NAGase) activities in the aorta of rats with renal hypertension were performed on "H?utchen" monolayer preparations. The aortic endothelial cells in renal hypertensive animals showed increased Ac-Pase and NAGase activities compared with those in control normotensive rats and tended to increase with advancing age. These results, like our previous data from spontaneously hypertensive rats (SHR), indicated that degeneration of endothelial cells, expressed by increased lysosomal enzyme activity, was accelerated by hypertension, and the possible participation of genetic factors in the activation of these enzymes in SHR was ruled out. Increased lysosomal enzyme activity may be involved in the development of other hypertensive vascular changes.     

Patency of different arterial and venous end-to-side microanastomosis techniques in a rat model

Microvascular anastomotic patency is the most important factor in determining a successful outcome in free-flap transfers. End-to-end and end-to-side techniques have been shown to provide equivalent arterial patency rates in clinical and basic science studies, and end-to-side anastomoses have been used extensively in microsurgical reconstruction. Nevertheless, the effect of venotomy shape on the patency of venous end-to-side anastomoses has not been previously reported. The purpose of this study was to compare the patency rates of end-to-side anastomoses using different techniques in both arteries and veins. In total, 104 Sprague-Dawley rats were subdivided into four groups. The rats were anesthetized, and anastomosis was performed on either the femoral artery or vein on the right with the left used as control. Vesselotomy was varied between an end-to-side hole and an end-to-side slit with patency measured immediately following surgery and at 2 weeks. No significant difference in patency or histology between these techniques was demonstrated in any group. We conclude there is no difference in patency rate between the two techniques in arterial or venous vesselotomies; however, in small vessels < 1.5 mm, the slit technique is technically easier, and clinical recommendations are given.     

Rats chronically injected with urine from Huntington's chorea patients do not striatal damage

Rats were injected subcutaneously for 147 consecutive days with large volumes of urine from control subjects and from patients with Huntington's chorea (HC) in an effort to test for presence of a possible neurotoxic substance in HC. No evidence of illness was observed in animals treated with HC urine, and their behavior did not differ from animals treated with control urine. After rats were sacrificed, striatum was examined for the biochemical and neuropathological changes seen in human striatum in HC. No deficiency of γ-aminobutyric acid content, nor reduction in activities of glutamic acid decarboxylase and choline acetyltransferase, was found in striatum of rats chronically treated with HC urine. Also, no significant differences were found between striatum of control and experimental rats by light or electron microscopy. These results neither support for exclude the possibility of a neurotoxic mechanism for the neuronal loss characteristic of HC.     

Extended exposure to continuous low intensity light abolishes the photosensitivity of retinal dopamine neurons

Male Sprague-Dawley rats were divided into 2 groups. One group (experimental) was housed for 6 months in continuous low intensity light while the other (control) was exposed to standard 14 hr light: 10 hr dark cyclic lighting conditions for the entire time. For both the control and experimental groups the light intensity was 350-700 Lux. After 6 months, the experimental rats were returned to cyclic lighting. At one week and again at 2 months the light aversion behavior of all rats was tested in a light/dark test box. The experimental rats chose the dark side of the box only 58% of the time while control animals preferred the dark 79% of the time. Since rats normally are nocturnal and avoid light, these results suggest that the experimental rats may have permanently lost a functionally significant portion of the ability to detect light. After the second behavioral test all rats were dark adapted and 15 hr later the effect of short term (30 or 60 min) exposure to light on DA turnover in one retina from each rat was assessed. The other retina from each rat was fixed and examined histologically. Light significantly enhanced the alpha methyl-p-tyrosine induced decline of DA in the retinas of the control rats but exerted no similar effect in the experimental animals. The retinal DA contents of the experimental rats were substantially depleted. Histological examination suggested that the outer nuclear layers of the experimental retinas were more severely damaged than those from rats exposed to continuous light for 4 months but still contained a few pycnotic photoreceptor nuclei and nearly normal looking inner neural layers. These results indicate that extended exposure to light eventually abolishes light aversion behavior and at this time there is also a loss of the photosensitivity of the dopaminergic amacrine neurons.     

End-to-end versus end-to-side microvascular anastomosis patency in experimental venous repairs

In this experimental study, venous end-to-end and end-to-side microvascular anastomoses in similar and diameter-discrepant vessels were compared. In 50 rats, end-to-end microvascular repair of the divided epigastric vein and end-to-side repair of the epigastric vein into the femoral vein showed 5-day patency rates of 75 and 88 percent, respectively. These data are not statistically different. In 20 rats, microvascular repair of end epigastric to end femoral veins (size discrepant) and end epigastric to side femoral veins showed 5-day patency rates of 50 and 85 percent, respectively. These data are statistically different (p less than 0.05). We conclude from these experimental data that end-to-side venous repairs may be useful in lowering the anastomosis thrombosis rate seen when size-discrepant veins are repaired.     

Experimental autoimmune encephalomyelitis in "low" and "high" interleukin 2 producer rats. I. Cellular basis of induction

Albino Oxford (AO) rats in comparison to the Dark August (DA) strain exhibit lower susceptibility to the induction of experimental autoimmune encephalomyelitis (EAE), and interleukin 2 (IL-2) production by their spleen and lymph node cells is significantly lower. The cellular analysis of these differences in the outcome of the EAE induction, possibly related to the differences in the IL-2 production, revealed different changes in the T cell subsets in the draining lymph node (DLN) and different cellular composition of the mononuclear infiltrates in the central nervous system (CNS). After the encephalitogenic challenge, the frequency of CD8+ T cells was much higher and the expansion of CD4+ T cells was much lower in the DLN of "low" IL-2 producer rats. AO rats have not shown any clinical sign of EAE, although histological lesions in the early phases of EAE (Day 7-9) were similar to those seen in diseased DA rats. CD4/CD8 T cell ratios and the number of cells bearing receptor for IL-2 (IL-2-R+ cells) and cells bearing class II MHC antigens (Ia+) were significantly lower in the mononuclear cell infiltrates of AO rats. These data are compatible with the notion that CD4+ IL-2-R+ encephalitogenic T cells induce clinical signs of EAE in susceptible animals and show that CD8+ T cells are present in a higher percentage in the lesions of the symptom-free AO rats.     

Obstructive apneas induce early activation of mesenchymal stem cells and enhancement of endothelial wound healing

Background

The aim was to test the hypothesis that the blood serum of rats subjected to recurrent airway obstructions mimicking obstructive sleep apnea (OSA) induces early activation of bone marrow-derived mesenchymal stem cells (MSC) and enhancement of endothelial wound healing.

Methods

We studied 30 control rats and 30 rats subjected to recurrent obstructive apneas (60 per hour, lasting 15 s each, for 5 h). The migration induced in MSC by apneic serum was measured by transwell assays. MSC-endothelial adhesion induced by apneic serum was assessed by incubating fluorescent-labelled MSC on monolayers of cultured endothelial cells from rat aorta. A wound healing assay was used to investigate the effect of apneic serum on endothelial repair.

Results

Apneic serum showed significant increase in chemotaxis in MSC when compared with control serum: the normalized chemotaxis indices were 2.20 ± 0.58 (m ± SE) and 1.00 ± 0.26, respectively (p < 0.05). MSC adhesion to endothelial cells was greater (1.75 ± 0.14 -fold; p < 0.01) in apneic serum than in control serum. When compared with control serum, apneic serum significantly increased endothelial wound healing (2.01 ± 0.24 -fold; p < 0.05).

Conclusions

The early increases induced by recurrent obstructive apneas in MSC migration, adhesion and endothelial repair suggest that these mechanisms play a role in the physiological response to the challenges associated to OSA.

     

Repeated exercise paired with "imperceptible" dead space loading does not alter VE of subsequent exercise in humans.

We employed an associative learning paradigm to test the hypothesis that exercise hyperpnea in humans arises from learned responses forged by prior experience. Twelve subjects undertook a "conditioning" and a "nonconditioning" session on separate days, with order of performance counterbalanced among subjects. In both sessions, subjects performed repeated bouts of 6 min of treadmill exercise, each separated by 5 min of rest. The only difference between sessions was that all the second-to-penultimate runs of the conditioning session were performed with added dead space in the breathing circuit. Cardiorespiratory responses during the first and last runs (the "control" and "test" runs) were compared for each session. Steady-state exercise end-tidal PCO(2) was significantly lower (P = 0.003) during test than during control runs for both sessions (dropping by 1.8 +/- 2 and 1.4 +/- 3 Torr during conditioning and nonconditioning sessions, respectively). This and all other test-control run differences tended to be greater during the first session performed regardless of session type. Our data provide no support for the hypothesis implicating associative learning processes in the ventilatory response to exercise in humans.     

Mechanisms involved in the adrenaline-induced blockade of milk ejection in dairy cattle

To elucidate mechanisms by which epinephrine (epi) blocks milk ejection in cattle, blood serum oxytocin (OT) concentrations were measured in four heifers before, during, and after milking following either intrajugular injection of 0.85% saline (S) or epi (3 mg). S did not affect OT concentrations. They peaked 2 min after milking-machine attachment. OT declined 3 min after milking commenced, reaching resting concentrations 10-60 min after milking. Milk yields were not altered by S. Epi did not influence significantly basal OT concentration. Yet, OT released to milking appeared less than the saline control. Peak OT concentration after epi and milking was reached 1 min after machine attachment. OT declined within 3 min after milking commenced. Milk yield was reduced 48% after epi. Jugular vein and carotid arterial OT concentrations and mammary blood flow (MBF) were measured simultaneously in four multiparous cows. Blood was collected before, during, and after milking following S or epi (50 micrograms). Jugular and carotid OT concentrations followed similar patterns for both treatments. Changes in carotid OT concentrations lagged behind those of the jugular vein by approximately 1 min. Elevated carotid OT concentrations were seen in two cows after milking and thought to be derived from non-hypothalamic-neurohypophysial sources. Epi (50 micrograms) did not reduce blood OT concentrations, but reduced MBF by 95%. Milking induced increases in MBF seen in controls, were not observed with epi, and milk yield was reduced by 56%. Our experiments suggest that epi may inhibit OT release to milking stimuli at pharmacological doses. At lower doses, epi exerts its effects peripherally by acutely reducing MFB, thus preventing physiological concentrations of hormone from reaching the myoepithelium. An intrinsic action of epi on the myoepithelial cells of cattle is unlikely, but cannot be ruled out at this time.     

Nitric oxide synthase expressions in ADR-induced cardiomyopathy in rats

In this study, we investigate Nitric oxide synthase (NOS) expressions in adriamycin (ADR)-induced cadiomyopathy in rats. Sixty male Wistar rats were randomly divided into two main groups: control and ADR groups. Myocardial histopathological observation was performed; Expressions of 3 isoforms of NOS genes were examined by RT-PCR analysis; Expressions of 3 isoforms of NOS protein was assessed by Western blot analysis. Myocardium exhibited intensive morphological changes after 8 weeks of ADR treatment. The expression levels of inducible NOS (iNOS) gene and protein were significantly increased in ADRtreated rats after 8 weeks of treatment and then slightly increased at weeks 9 and 10. No significantly difference of neuronal NOS (nNOS) or endothelial NOS (eNOS) gene and protein were observed in the myocardium obtained from the control rats and ADR-injected rats at any time point. iNOS gene expression is selectively induced by ADR in heart. The upregulation of iNOS gene and protein may be somehow correlated with morphological changes seen in heart of rat treated with ADR.     

Osteocutaneous flap prefabrication in rats

Composite tissue defects may involve skin, mucosa, muscle, and bone together or in combinations of two or three of these tissues. Defects involving bone and skin are frequently encountered. Osteocutaneous flaps may be used to reconstruct these composite tissue defects. Sometimes, it is not possible to obtain a vascular osteocutaneous flap. Another way of producing an osteocutaneous flap that has the desired feature is prefabrication. Prefabrication of osteocutaneous flaps can be performed in two ways: (1) a vascularized osseous flap may be grafted with skin and (2) an osteocutaneous flap can be prefabricated by implanting an osseous graft into an axial island flap. There are many articles describing osteocutaneous flap prefabrication, but there is no comparison of both methods in the literature. As an experimental model for osteocutaneous flap prefabrication, rat tail bone was chosen. For the experiments, five groups were formed. Each group contained 10 rats. In the first experimental group, a vascularized osseous segment was skin grafted and an osteocutaneous flap was prefabricated. In the second experimental group, an osseous graft was implanted into an axial skin flap. To compare viability of skin and bone components of the two prefabrication groups, vascularized tail bone was elevated with overlying skin in the third group, a bone flap was elevated in the fourth group, and a skin flap that had been prefabricated by using vascular implantation was elevated in the fifth group. The authors examined five rats in each group by microangiography at the end of 4 weeks. On microangiographic analysis, all groups showed patency of vascular pedicles. There was no difference among the groups from the point of view of vascular patency and bone appearance. Bone scintigraphy was performed on the five rats in each group. On bone scintigraphic scans, the bone component of flaps was visualized in all groups except for group 5. The mean radioactivity value on the flap side was 10,362 +/- 541.1 in group 1, 10,241 +/- 1173 in group 2, 10,696 +/- 647.1 in group 3, and 10,696 +/- 647.1 in group 4. When the radioactivity values on the flap side were compared, no statistically significant difference among groups was seen, except for group 5 (p < 0.05). To evaluate bone metabolic activity, the bone component of flap and remaining last tail bone was harvested and the radioactivity of each specimen was measured with a well-type gamma counter. The parameter of percentage radioactivity in counts per minute per unit per gram of tissue was calculated. The value of the bone component of the flap side and the value of normal bone were estimated and results were compared. The mean result was 0.86 +/- 0.08 in group 1, 0.88 +/- 0.07 in group 2, 0.87 +/- 0.07 in group 3, and 0.81 +/- 0.04 in group 4. The difference among all groups was not statistically significant. Histologic examination was performed on all rats in each group and demonstrated that the bony component was viable, showing a cellular bone marrow, osteoblasts along bony trabeculae, and vascular channels in bone-containing groups. There were no significant microangiographic, histologic, or scintigraphic differences between the two experimental methods.     

Is order of voluntarily entrance to milking parlour related to Toxoplasma gondii infection in sheep—A brief note

Toxoplasma gondii is a parasite influencing behaviour of its hosts. The parasite is often present in sheep flocks without clinical symptoms. The order of moving to the milking parlour was reported to be non-random in domestic bovids. The aim of this study was to investigate if milking order is related to T. gondii infection in sheep. The study was performed on 41 ewes milked twice a day. Milking order was noted during 7 consecutive days. The indirect fluorescent antibody test (IFAT) was used to detect antibodies (IgG + IgM) in sera of sheep. Titers ≥8 were considered positive. Moreover, in case of positive sera a test for IgM was conducted. The antibodies to T. gondii were found in 53.65% of the investigated sheep, but IgM were not found in any sheep. Infected sheep entered the milking parlour significantly later (mean position at milking 24.89) than uninfected animals (16.40; r = 0.43, p = 0.006). Results of this study suggest that behaviour of sheep is related to T. gondii infection. However, it is not clear if the phenomenon has any adaptive value for the parasite.     

Mast cell "disappearance" in chronic murine graft-vs-host disease (GVHD)-ultrastructural demonstration of "phantom mast cells"

Mast cells were studied during the induction of chronic graft-vs-host disease (GVHD) induced in mice across minor histocompatibility barriers. B10.D2 spleen cells (or control BALB/c cells) were injected into irradiated (600 rad) BALB/c recipients. Serial skin biopsies were taken over 26 days, during which time changes occurred resembling scleroderma, namely, dermal fibrosis, a mononuclear cell infiltrate, and loss of fat and appendages. Mast cells, when stained with toluidine blue, "disappeared" from GVHD, but not from control skin. Ultrastructural analysis showed that mast cells in GVHD skin were indeed present but underwent degranulation. Some mast cells showed only pale expanded sacs, indicating granule depletion. Because these cells could not be seen by toluidine blue staining but were plainly present, we have called them "phantom mast cells." Cellular activation occurred in many GVHD mast cells as shown by increased cytoplasmic activity, with numerous Golgi complexes, ribosomes, granular endoplasmic reticulum, and small vesicles. No identifiable mast cells were seen after day 19. No significant changes were seen in the mast cells of syngeneic control mice. We believe that immunologic processes in chronic GVHD cause a slow release of mast cell granule contents, which is different from anaphylactic degranulation. The depleted mast cells (invisible by toluidine blue staining) are also activated, perhaps in an attempt to replete their stores of granule contents. We discuss the relation of mast cell changes to fibrosis.