Fibrinoid Material Research Articles

A clinicopathological study of three cases of severe acute respiratory syndrome (SARS)

SummaryAimsThe severe acute respiratory syndrome (SARS) caused a large outbreak of atypical pneumonia in Beijing, China from early March 2003. We report the pathological features from three patients who died of SARS.MethodsAutopsies were performed on three patients who died 9–15 days after the onset of the illness, and the clinical and laboratory features reviewed. Tissue sections were stained with haematoxylin and eosin (H&E), and in situ reverse transcriptase polymerase chain reaction (RT–PCR) on lung sections was performed using SARS coronavirus-specific primers.ResultsThe typical gross pathological change in the lungs was diffuse haemorrhage on the lung surface. Histopathological examination revealed serous, fibrinous and haemorrhagic inflammation in most pulmonary alveoli, with capillary engorgement and some capillary microthrombosis. The pulmonary alveoli were thickened with interstitial mononuclear inflammatory infiltrates, diffuse alveolar damage, desquamation of pneumocytes and hyaline-membrane formation; fibrinoid material and erythrocytes were present in alveolar spaces. There were thromboemboli in some bronchial arterioles. Haemorrhagic necrosis and reduced numbers of lymphocytes were observed in lymph nodes and spleen. In situ RT–PCR detected SARS coronavirus RNA in type II alveolar cells, interstitial cells and bronchiolar epithelial cells from all three patientsConclusionsSevere immunological damage in lung tissue is responsible for the clinical features of SARS.

Can the diagnosis of NSAID-induced or Hp-associated gastric ulceration be predicted from histology?

We studied the question whether NSAID/ASA-induced ulcerations can be identified in human gastric biopsy material on the basis of ischaemic necrosis. Biopsies of 208 patients with gastric ulcers were assessed histologically. 29 patients were excluded from the study. NSAID/ASA ulcers were diagnosed when a homogeneous eosinophilic ischaemic necrosis was found. Helicobacter pylori-(Hp-) induced ulcers were diagnosed when non-homogeneous fibrinoid necrotic material containing granulocytes and cell debris was noted. The histological diagnosis was compared with the data on medication use, endoscopy and clinical history. 121 of the 179 patients included had a medical history on NSAIDS/ASA. From the 60 patients taking NSAIDS/ASA with no histologic evidence of Hp all (100 %) were identified by the histology of the necrosis. From the 61 patients taking NSAID/ASA and histologic evidence of H. pylori 40 (66 %) were identified by histology. From the 58 patients with no such medication 41 were Hp-positive and correctly identified by histology in 31 cases (76 %). The sensitivity of the histologic diagnosis of NSAID/ASA-induced ulceration was 85 %, and its specificity 53 %. The results of our study show that a high percentage of the NSAID/ASA-induced ulcers of the stomach can indeed be correctly diagnosed at histology. In conclusion the underlying aetiopathogenesis of gastric ulcerations (NASID/ASA vs. Hp) can be uncovered in a large proportion of patients based on histological examination.

Parathion, a Cholinesterase-Inhibiting Plaguicide Induces Changes in Tertiary Villi of Placenta of Women Exposed: A Scanning Electron Microscopy Study

The objective of this work was to describe the anatomy of placentas from women who were at risk of exposure to parathion during their pregnancy, when examined with the light and scanning electron microscopes. Twenty term placentas were analyzed; 10 from women living in an agricultural area, who were at risk of exposure to parathion during their pregnancy, and 10 from women living in an urban area, not expressly exposed to pesticides. Each sample was examined with both light and scanning electron microscopes. Cholinesterase activity was significantly reduced in blood from women of the exposed group. In some placentas of women exposed to parathion, recent microinfarctions, microcalcifications and increased deposition of fibrinoid material were seen, along with a larger proportion of atypical characteristics of villi, such as bullous and balloon-like formations with nonhomogeneous surface, and other areas devoid of microvilli. These observations suggest that in chronic exposure to pesticides, the rate of atypical characteristics of placental villi increases, which could be related to changes in the fetus biology. In this study, one newborn from the exposed group showed intrauterine growth retardation and another one, some signs of hypoxia.

Complex Vascular Lesions at Autopsy in a Patient With Phentermine-Fenfluramin

To the Editor.—In the June 1999 issue of the Archives, Strother et al1 reported the case of a middle-aged woman who had ingested phentermine and fenfluramine for weight reduction during 8 months. The lesions of pulmonary muscular arteries shown in Figure 1, A and B, which the authors interpreted as focal organizing thrombi, are, in my opinion, plexiform lesions. The lesion in Figure 1, A, is intimal hyperplasia, and Figure 1, D, represents arterial necrosis. These lesions correspond to grades IV, II, and VI, respectively, in the grading system established by Heath and Edwards2 for the lesions of muscular arteries of 100 μm to 1000 μm diameter in pulmonary hypertensive vascular disease or to pulmonary plexogenic arteriopathy as proposed by a World Health Organization Working Group.3 My opinion is established on the morphologic study of the lungs of 37 patients who died in Switzerland after having ingested aminorex fumarate (another weight-reducing pill)4 during the so-called aminorex epidemic reviewed by Gurtner.5 Pulmonary hypertensive vascular disease affected 582 patients in Austria, former West Germany, and Switzerland during a limited period: from 1965, when the drug was introduced, until 1968, when it was withdrawn from the market. None of our cases showed arterial thromboses.In 2 cases of phentermine-related pulmonary hypertensive vascular disease submitted for assessment (unpublished data), I found similar vascular lesions. However, none of the patients (aminorex or phentermine cases) showed any correlation between the severity of the lesions and the drug intake (quantity or duration).In the absence of any serious experimental model published, the mechanism by which the lesions related to anorexigens (aminorex, phentermine, or fenfluramine hydrochloride) remains unexplained. One can only hypothesize that in some people (about 0.2% in the aminorex cases), some factors did cause an increase in the tonus of muscular pulmonary arteries, which was followed by a vasospasm, resulting in an endothelial lesion on which fibrinoid material was deposited, producing intimal proliferation. The latter, rich in myointimal cells and smooth muscular cells, might have contributed to the aggravation of the pulmonary hypertension induced by the vasospasm.I agree with the question Strother et al raised about the risk-benefit operation of the new anorexigens, which in turn leads to the more serious inquiry into unrecognized cases of pulmonary hypertensive disease in the countries where these drugs are marketed.

The role of trophoblast in the physiological change in decidual spiral arteries.

The remodelling of the maternal uterine spiral arteries during pregnancy, known as physiological change, is critical for the normal growth and development of the fetus. Controversy has surrounded the part played by fetal trophoblast in the transformation of these spiral arteries. To address this debate, a histological and immunochemical comparison of blood vessels from the implantation sites of human pregnancies of early gestation with uterine tissue where trophoblast was absent was performed. Results showed that true physiological change, with the features of medial necrosis and deposition of fibrinoid material, only occurred in the presence of trophoblast. In addition, it was found that subpopulations of trophoblast contribute differently in the process. Interstitial trophoblast-mediated destruction of the arterial media precedes replacement of the endothelial cells by endovascular trophoblast.

An experimental rat model of salt-sensitive hypertension; biochemical and morphological parameters and sympathetic nervous system.

The objective of the study was to outline the characteristics of the development of hypertension and some neurohumoral, haematological and morphological factors contributing to development of high blood pressure in a genetic model of salt-sensitive rat. Characteristics of Dahl salt-sensitive (DS) rats, as compared to their Dahl salt-resistant (DR) controls were as follows: 1) DS rats display higher blood pressure and lower heart rate compared to DR rats as early as 1 month of age at weaning). They gradually develop hypertension at 2 months of age, irrespective of diet. Low-Na diet (0.5% NaCl) does not prevent hypertension but delays its development and ameliorates it. High Na-diet (8% NaCl) exacerbates hypertension. 2) DS rats have retardation in body weight gain. They develop mild hypochromic anaemia. 3) After 2 months of Na loading (3 months of age), DS rats express significantly increased Na and water retention and increased plasma volume by 15% compared to 2.8% increase in DR rats on high-Na diet. 4) DS rats showed renal parenchymal lesions, more pronounced after Na-loading, focal atrophy of cortical tubules, mesangial matrix expansion and glomerulosclerosis. Consistent with high blood pressure were changes in renal arterioles, fibromuscular proliferation, deposition of fibrinoid material in intima. 5) Sodium loading produced increased activity of the sympathetic nervous system (SNS), and sodium restriction reduced SNS responsiveness.

The hemolytic uremic syndrome as a complication of adriamycin nephropathy

Rats treated with two injections of adriamycin (week 0 and week 12) developed glomerusclerosis and severe tubulointerstitial lesions as described in the literature. In addition, a number ofglomerular alterations were present. These included capillary loop dilation, insudation of eosinophilic material, necrosis, duplication of the glomerular basement membrane, severe mesangiolysis with disruption of the mesangial matrix and segmental double-contours. The renal arterioles and interlobular arteries showed endothelial cell swelling. The subendothelial space was infiltrated by fibrinoid material and there was intensive fibrinoid necrosis of the wall of both arteries and arterioles extending into the glomerular tuft. These alterations were very similar to those observed in the hemolytic uremic syndrome. This observation suggests that the two injections of adriamycin, with a long interval in between them, might induce renal lesions similar to those observed in the hemolytic uremic syndrome.

Cytologic diagnosis of complicated pulmonary unilocular cystic hydatidosis. A study of 131 cases.

To determine the value of cytochemical stains and microscopic techniques for the detection of true hydatid elements (primary cytologic criteria) and to evaluate the efficacy of granulomatous elements (secondary cytologic criteria) for the diagnosis of complicated pulmonary unilocular cystic hydatidosis (CPUCH). Sputum, bronchial washing and bronchial brushing specimens obtained from 131 patients with a presumptive diagnosis of CPUCH were reviewed. CPUCH was histopathologically proven in 111 of 131 patients. Scolices were found in 11 patients in Papanicolaou-EA65 (PAP-EA65)-stained slides. Special stains and dark field microscopy (DFM) did not make any additional contribution to specifying the nature of the scolexlike objects. Hooklets were found in 26 patients in PAP-EA65-stained slides. Masson's trichrome stain and DFM revealed hooklets in 37 and 50 cases, respectively. Laminated membrane fragments were found in 14 patients in PAP-EA65-stained slides. Gomori's methenamine silver stain and DFM demonstrated laminated membrane fragments in 25 and 33 cases, respectively. Secondary cytologic criteria, such as multinucleated giant cells, degenerated squamous cells, dyskaryotic squamous cells, excessive amounts of eosinophils, plasma cells, lymphocytes, histiocytes, necrotic debris, fibrinoid material and erythrocytes, were considered to be suggestive of hydatid disease when there are more than three such factors in patients with a presumptive diagnosis of CPUCH. Though DFM examination is superior to cytochemical stains used in this study, both cytochemical stains and DFM are useful in increasing the sensitivity of cytologic detection of true hydatid elements, especially hooklets and laminated membrane fragments. They should be used as auxiliary techniques. Secondary cytologic criteria are suggestive of the diagnosis of CPUCH, and special care should be taken when there are more than three such factors in cytologic specimens.

Targeted disruption of the Wnt2 gene results in placentation defects.

Wnt genes have been implicated in a range of developmental processes in the mouse including the patterning of the central nervous system and limbs. Reported here for the first time is the expression of Wnt2 in the early heart field of 7.5-8.5 dpc (days post-coitum) mouse embryos, making Wnt2 a potentially useful gene marker for the early stages of heart development. Expression was also detected in the allantois from 8.0 dpc and at later stages in the placenta and umbilicus. Mice deficient in Wnt2, generated by gene targeting, displayed runting and approximately 50% died perinatally. Histological analysis revealed alterations in the size and structure of placentas from these mice from 14.5 dpc. The placental defects were associated primarily with the labyrinthine zone and included oedema and tissue disruption and accumulation of maternal blood in large pools. There was also an apparent decrease in the number of foetal capillaries and an increase in the amount of fibrinoid material in the Wnt2 mutant placentas. These results suggest that Wnt2 is required for the proper vascularisation of the mouse placenta and the placental defects in Wnt2-deficient mice result in a reduction in birthweight and perinatal lethality.

Small, freshly arrived histiocytes in cutaneous and mucosal herpetic lesions.

We report on the predominance of a special type of small histiocyte in the inflammatory infiltrate accompanying herpetic bullae. These histiocytes, which have previously been taken to be neutrophils, are freshly arrived cells with a hitherto unknown function. Until now, they have been found only in Sweet's syndrome and erythema nodosum where they form Miesscher's radial granulomas. Similar small histiocytes were found in half of those herpetic lesions with intact bullae, and in over two-thirds of ulcerated lesions in which these cells formed a palisade in the fibrinoid material covering the floor of the ulcerated vesicles. Small histiocytes, admixed with neutrophils, were in close proximity to virally infected keratinocytes. Immunohistochemical analysis confirmed their histiocytic nature. With the exception of ecthyma contagiosum (orf), similar small histiocytes were not found in other viral infections or in nonspecific ulcers of the skin. In cases of herpetic folliculitis, small histiocytes showed massive epidermotropism towards hair follicle epithelium. We conclude that cutaneous and oral herpetic infections represent yet another disease in which small, freshly arrived histiocytes occur. They may be involved in antigen presentation, or in killing of infected keratinocytes.

Kikuchi-Fujimoto Disease: A Clinicopathologic Study of Six Cases in Riyadh, Saudi Arabia

Kikuchi-Fujimoto Disease: A Clinicopathologic Study of Six Cases in Riyadh, Saudi Arabia

ERYTHEMA ELEVATUM DIUTINUM

A 57‐year‐old woman presented with symmetrical reddish‐brown plaques on the entire skin, especially the extremities. The lesions differed in size and shape, and their consistency ranged from soft to tight‐elastic, to hard in the older lesions (Fig. 1). The forearms and the dorsae of the hands and feet were covered with confluent plaques; some of these had an isolated nodular lesion on top. The lesions on the arms were papular‐nodular, arranged in rows to form “cords” with “pseudokeloid” appearance (Fig. 2). On the face, around the cheeks, the wings of the nose, and the ears, there were purplish nodular lesions and plaques.The lesions first appeared 14 years ago in the winter as lentile‐sized, slightly reddish papules on both legs. These lesions disappeared spontaneously during the summer and returned the following winter. For 4 years the lesions followed this pattern of appearing and disappearing, leaving residual pigmentation. The patient reported that at each recurrence the lesions were larger and darker. Subsequently, the lesions had become permanent without any improvement during the summer and had also spread to the upper limbs and trunk. For the past 4 years the patient has had arthralgia of the large joints, swelling of the lower extremities, burning and pain in the lesions themselves. These symptoms became more evident in the evening and after exposure to cold.A biopsy specimen of a recent lesion showed a dermal perivascular infiltrate comprised mainly of neutrophilic granulocytes and histiocytes and a few eosinophils. The vessels appeared dilated with swelling of the endothelial cells (Fig. 3). In and around the vessel walls an eosinophilic deposit of fibrinoid material was noted.Electronmicroscopic examination revealed macrophages with secondary lysosomes containing electrondense, osmiophilic, probably lipid material, in the perivascular infiltrate. lnterdigitate cells, juxtaposed with the lymphocytes among the infiltrate cells were also seen (Fig. 4).Direct immunofluorescence (DIF) revealed linear IgA deposits at the dermoepidermal junction. Direct immunofluorescence on healthy perilesional skin after histamine injection1 showed IgA, C3, and fibrinogen at the perivascular level in the superficial dermis and at the dermoepidermal junction with granular appearance.Cutaneous fibrinolytic activity (CFA) evaluated with Todd's autohistographic method1, modified by Lotti et al.2, was reduced by 80% compared to that of healthy subjects.Findings of other laboratory tests are listed in Table 1. Relevant investigations showed a decrease in fibrinogen, positive protein C and RA tests, the presence of cryoglobulin, and an increase in serum |gA.| Circulating immune complexes were detected and glucose‐6‐phosphate‐dehydrogenase (GG‐PD) was slightly low. The tests of clotting function showed some changes due to increased platelet aggregability from exogenous adenosine diphosphate (ADP), a slight reduc‐tion in fibrinogenemia due to the presence of D‐dimers and other products of fibrinogen degradation, suggesting a state of chronic intravascular coagulation.Treatment was begun with diaminodiphenylsulfone (50 mg/day), which was suspended because of adverse reac‐tions (headache and nausea) and was replaced by clofa‐zimine (starting dose 200 mg/day). Improvement in the sub‐jective symptoms and healing of many lesions with residual pigmentation was noted.

Expression of nitric oxide synthase in human trophoblast

Histochemical investigations have been carried out on 134 placentas, 3 to 20 weeks old, collected from the service for the requested interruption of pregnancy. The results, expressing the incidence of avascularity, stromal edema, and epithelial stratification, demonstrate the association o f the three histologic elements in producing the characteristic appearance of the “molar type.” This normally lasts up to the age of 12 to 14 weeks. Observations were also made on the transformation of intervillous cytotrophoblast masses into P.A.S.-positive fibrinoid material. This process starts at the eighth to tenth week of gestation, and becomes general at the same time as the vascularization of the villi. Hence, fibrinoid degeneration appears to be evidence of placental maturation, contributing to the formation of intervillous “pseudoinfarction” and indirectly to functional changes in the villous syncytium.

Endometrial effects during hormone replacement therapy with a sequential oestradiol valerate/cyproterone acetate preparation

Three sequential oestradiol valerate (E 2V) and cyproterone acetate (CPA) combinations based on 11 days of oestrogen and 10 days of oestrogen-progestogen administration were investigated during hormone replacement therapy in two prospective, double-blind randomized trials. Treatment A comprised 2 mg E 2V and 1 mg CPA, treatment B, 1 mg and 0.5 mg and treatment C, 2 mg and 2 mg, respectively. During treatment A hot flushes ( P < 0.0001), night sweating ( P < 0.0001), depression ( P = 0.0001), dizziness ( P = 0.0001) and insomnia ( P = 0.003) decreased significantly. The only side effect was breast tenderness, which was experienced by 18% of the women. Weight and blood pressure, thyroid, adrenal, liver and kidney functions, parathyroid hormone and vitamin D, platelets and blood cell counts did not change during the 12 months of therapy. In the women who received treatment A the menstrual flow became less abundant during the early months of treatment ( P < 0.0001), the menses being scanty in around 30% of the women, while some 10% had amenorrhoea. Spotting occurred in 10–20% of the subjects. Endometrial biopsies were atrophic in 10% of the women, whereas a normal secretory phase was observed in 45% and irregular secretion in 45%. After careful analysis using visual analog scales, these findings were interpreted as indicating a high-normal progestational effect. In comparison with the pattern observed in normal menstrual cycles the women who received treatment A had a more heterogenic glandular epithelium, with more papillae, larger stromal cells, a more pronounced decidual reaction and more fibrinoid material. No cases of hyperplasia were seen. Treatment B was less effective than treatment A in relieving climacteric complaints. Irregular bleeding was troublesome in over 20% of cases and amenorrhoea occurred in 50%. Endometrial biopsies were atrophic in 57% of the women. The effectiveness of treatment C in alleviating flushes, sweating, dizziness and depression was the same as that of treatment A. The decrease in menstrual flow during the early months and the incidence of amenorrhoea (approx. 10%) and atrophic endometria (approx. 10%) were comparable. Detailed analysis revealed that C had an even stronger progestational effect than A. It was concluded that A was the treatment of choice in comparison with B and C. It proved highly effective in treating climacteric complaints, had no side effects apart from breast tenderness, provided good cycle control and induced a physiological secretory transformation of the endometrium. The 1 mg CPA dose has a high-normal progestational effect, which may be considered an advantage for the prevention of endometrial hyperplasia.

Maternal floor infarction: Relationship to X cells, major basic protein, and adverse perinatal outcome

OBJECTIVE: Maternal floor infarction of the placenta is characterized by gross placental abnormalities and histologic evidence of X-cell proliferation. Previously, pregnancy-associated major basic protein has been localized to the placental X cell and identified at elevated levels in serum and amniotic fluid in all normal pregnancies. Here we test the hypothesis that pregnancy-associated major basic protein is localized to the X cells in maternal floor infarction and that it contributes to the pathophysoogc features of pregnancies complicated by maternal floor infarction. STUDY DESIGN: Seven patients with eight pregnancies complicated by maternal floor infarction were evaluated. We analyzed placental tissue, serum, amniotic fluid, and placental cyst fluid for pregnancy-associated major basic protein. RESULTS: Placental tissue from pregnancies complicated by maternal floor infarction had increased numbers of X cells and fibrinoid material that occupied or surrounded degenerating villi and that stained intensely for pregnancy-associated major basic protein. Serum pregnancy-associated major basic protein levels were variable and likely cannot be used to predict the occurrence of maternal floor infarction. CONCLUSION: Pregnancy-associated major basic protein, a potent cytotoxin, is localized to X cells and is deposited in close proximity to chorionic villi in maternal floor infarction and may contribute to the pathophysiology of this disorder.

Chronic renal allograft rejection: the significance of non-MHC alloantigens.

We studied the role of polymorphic endothelial antigens other than MHC in antibody-mediated chronic renal allograft rejection in two models. In the first model, donor Lewis rat kidneys were transplanted into BN recipients that had been made tolerant for donor class I antigens at the B cell (antibody) level. In this setting Lewis kidney grafts were chronically rejected with stable renal function but increasing proteinuria (> 100 mg/24 h). Rejected graft tissue showed mononuclear cell infiltration and the presence of glomerular vasculonecrotic lesions with fibrinoid material, associated with IgG and IgM deposition, but with absent or weak C3 binding. Graft endothelium showed no expression of MHC class II antigens. Serum antibodies were not reactive with donor class I antigens, but did react with endothelial non-MHC alloantigens. In the second model, more direct information on the role of endothelial non-MHC alloantigens in renal allograft rejection was obtained by transplanting Lewis 1 N kidneys into unmodified BN recipients (MHC-matched transplants). Here, similar to the first model, the animals developed severe proteinuria with stable renal function. Histopathological examination showed mononuclear cell infiltration and deposition of IgM and IgG along the glomerular vasculature, but this time in the presence of strong C3 reactivity. However, glomerular vasculonecrotic lesions with intense fibrin deposition were not observed. The data showed that although clinically the two kidney transplantation models used gave similar chronic rejection phenomena, histopathologically some striking differences were observed in the glomeruli. The precise mechanisms effecting chronic rejection of the grafts is still a puzzle. However, immune reactivity against graft (endothelial) non-MHC antigens may play a significant role.

結核性中耳炎の８例について

Eight cases (10 ears) of tuberculous otitis media are reported. These patients visited our clinic between 1988 and 1989. Seven of the 8 cases were previously treated as chronic otitis media at some other E. N. T. clinics. As five of these 8 cases were once treated in a certain clinic, iatrogenic implanted infection at that clinic was strongly suspected. Characteristic features of the symptoms were remedy-resistant otorrhea, otalgia, progressive hearing loss and facial paralysis. Important local findings for diagnosis were pale granulation tissue covered with thick fibrinoid material and presence of bare bone on the promontory. Combined use of antituberculous medicines, such as isoniazid, ethambutol, rifampicin, was effective for treatment. Although facial paralysis and progressive hearing loss occurred during the use of these medicines in the non-operated group, none of these complications were seen in patients who had had surgery before the use of these medicines. Eradication of the infection by surgery may be preferable in some cases of tuberculous otitis, especially in cases with bone erosion on the CT images.

Arteritis in equine fetuses aborted due to equine viral arteritis.

Arteritis in equine fetuses aborted due to equine viral arteritis.

Histology of the adult mouse oviduct and endometrium following a single prenatal exposure to diethylstilbestrol.

Light microscopy was used to examine the oviduct and endometrium of offspring from mice administered DES (10 micrograms/kg in 0.1 cc of corn oil, subcutaneously) or corn oil alone on Day 15 of gestation. Offspring were sacrificed at 5, 7 and 9 months of age. Oviduct changes in DES exposed offspring included numerous abnormal secretory cells which lined the mucosal folds of the isthmus. These cells contained a distinct granular cytoplasm which was eosinophilic and a nucleus displaced towards the apical surface. In addition both the ampulla and isthmus had mucosal folds which extended to the serosal surface and an accumulation of subepithelial fibrinoid material. Endometrial changes included squamous metaplasia of both the surface and glandular epithelial layer as well as extensive cystic glandular hyperplasia. In addition the endometrial connective tissue stroma exhibited fibrinoid accumulation. These changes may reflect an altered endocrine environment resulting from ovarian abnormalities during adulthood.

Plasmodium berghei: Histology, immunocytochemistry, and ultrastructure of the placenta in rodent malaria

The pathological changes associated with malarial infection in pregnancy were studied in rats and mice infected with Plasmodium berghei at different stages of gestation. Histopathological and ultrastructural studies of infected placentae near term in both species revealed disruption of architecture with gross thickening and necrosis of cells in the labyrinthine zone and fibrosis of the trilaminar trophoblast separating the maternal and fetal circulations. In the mouse, the extent of histopathological alterations in infected placentae ranged from the presence of immature erythrocytes in the fetal circulation in low grade maternal infection, to the marked deposition of fibrinoid material on the trilaminar trophoblast and inflammatory masses in severely infected placentae. In the rat, histopathological aberrations in the placentae were marked by placental stroma edema, fibrosis, and cellular infiltration. Immunohistological studies of cryostat sections of placentae from infected animals showed more parasites and pigment in infected mouse placentae than in the corresponding rat organ, but in both species parasites and pigment were largely confined to the maternal blood spaces and were only occasionally found in necrotic areas of trophoblast. No clear differences were observed between infected and control placentae in terms of the amount of IgG, IgM, or IgA which were each present in various amounts. These observations and the rarity of congential malaria in the animals indicate that the placenta constitutes a major barrier to infection of the fetus. However, the pathological aberrations in the infected placentae may impose a biochemical stress upon the fetus which may account for the low birthweight, the increased frequency of abortion, and the greatly increased maternal and fetal death rates observed in malaria.