Helmuth Sprinz

Penetration of Erythrocytes by Merozoites of Mammalian and Avian Malarial Parasites

Entry of merozoites of Plasmodium berghei yoeli and of P. gallinaceum into erythrocytes has been elucidated by electron microscopy. Merozoites approach host cells with the conoid leading the way. At the point of contact between the anterior pole of the parasite and the host cell a focal depression of the red cell membrane forms, which deepens as the merozoite advances. The continuity of the host cell membrane is not disrupted. With deeper invagination of the red cell membrane the resulting cavity conforms to the shape of the merozoite. The site of initial parasite contact forms a relatively constricted orifice through which the posterior portion of the parasite passes. Later the edges of this orifice fuse and the parasite now lies in a vacuole inside the host cell. At this stage the merozoite undergoes a transformation and dedifferentiation. The pellicle loses the characteristic thick inner membrane. The parasite becomes rounded and the conoid and paired organelles are no longer discernible. Trophozoite development is initiated. This sequence of events unequivocally establishes the origin of the parasite membrane envelope and the origin of the space separating the two membranes. The outer membrane is derived from the plasmalemma of the host red cell; the inner is the covering of the parasite.

Histopathology of the upper small intestines in typhoid fever. Biopsy study of experimental disease in man.

T HE RECOGNITION Of the role of the small bowel as a target organ in typhoid fever goes back to the beginning of the 19th century. Special at tention has been paid, ever since, to the morphologic alteration of the lymphatic nodules in the intestinal mucosa, in par t icular to the changes in Peyers patches. In contrast, the histologic changes of the mucosa proper are still a largely unexplored aspect of the disease. One of the [actors responsible for this state of affairs is the exclusive host specificity of man for Salmonella typhosa. Of all the animals tested so far in the laboratory, only the anthropoid apes respond to an oral typhoid infection with tissue changes akin to those seen in typhoid fever in man. This has resulted in almost complete reliance on human necropsy findings for the classic and standard descriptions of histologic changes of the gut in typhoid [ever. Unfortunately, intestinal tissues are most prone to postmor tem autolysis, a process defying a detailed analysis of mucosal alterations. More importantly, death in typhoid has to be considered a complication, usually occurring late in the disease, and findings obtained at autopsy do not necessarily reflect the lesions present in the early phases of the disease. At present, an indication of the dynamic morphologic events can be gained by examining intestinal mucosaI biopsies as infections proceed in the h u m a n subject. However, since intestinal,biopsy technics are appl ied mainly in countries with a low incidence of typhoid, such cases have only rarely been studied, and these infrequent observations on randomly obtained specimens could not answer questions of the pathogenesis and histopathology of the early intestinal lesions in typhoid [ever. I t is the purpose of the present study to furnish additional information in this area. This investigation was a by-product of a long-term stud), conducted in hu-

Comparative fine structure study of the gametocytes of avian, reptilian, and mammalian malarial parasites

The fine structures of the gametocytes of various malarial parasites were investigated and compared. The malarial parasites studied include Plasmodium lophurae, P. cathemerium, P. gallinaceum, P. pinotti, P. elongatum (all avian parasites), P. floridense (reptilian parasite), and P. knowlesi and P. cynomolgi (mammalian parasites). The gametocytes of these malarial parasites can be distinguished from the parasites of the asexual stages on the basis of the fine structures. A three-layered pellicle is very pronounced in the gametocytes of avian and reptilian malarial parasites, but less so in those of mammalian parasites. Gametocytes of avian and reptilian parasites differ from mammalian ones by their distinct mitochondria and round osmiophilic bodies, whereas the mammalian parasites show double membrane-bounded structures, possibly a mitochondrial equivalent, and elongated osmiophilic bodies. The macrogametocyte differs from the microgametocyte in that the former possesses more ribosomes, more developed endoplasmic reticulum, and more osmiophilic bodies than the latter. In addition to these differences, the mature microgametocyte shows electron dense aggregates in the nucleus and kinetosomes in the cytoplasm. A possible origin of the gametocytes from asexual merozoites is also discussed.

The Role of the Diaphyseal Medulla in the Repair and Regeneration of the Femoral Shaft in the Adult Cat

1. A surgical procedure is described which permits selective removal of the medulla froms the diaphysis of the cat femur and the study of the role of marrow elements in bone regenerations and repair. 2. In this experimental model, endosteal-callus formation, in the presence of marrow, precedes and exceeds periosteal-callus formation in the healing of a partial osteotomy without displacement. Cartilage was formed infrequently in the reactive bone callus and only after severing of the fibrous portions of the periosteum. 3. After removal of the medulla, residual narrow elements in the distal and proximal metaphyses and in the surviving endosteum of the Haversian and Volkmann canals appeared to initiate the repair processes which led to complete reconstitution of the medulla. The sequence of events during bone repair repeated the phases of embryonic membranous-bone development. The restorations of the medulla and its contributions to bone healing emphasize the importance of its role osteogenesis. 4. The disruption of the nutrient vessels during removal of the diaphyseal medulla was followed by reorganizations of the greater portions of the cortex of the diaphysis associated with marked though transient periosteal new-bone formation. The response elicited resembled that seen in hypertrophic pulmonary osteoarthropathy. As healing progressed the periosteal new bone was partly resorbed and partly reintegrated into the remodeled cortex of the diaphysis. 5. The experimental offers opportunities for the study of bone inductions and for the testing of substances which might enhance or delay bone repair.

Studies of the influence of estradiol and growth hormone on the hypophysectomized immature rat epiphyseal cartilage growth plate

Abstract These studies were designed to ascertain the differential effect of estrogen (E 2 ) on epiphyseal maturation and growth of the long bones. The influence of treatment with estrogen alone, growth hormone alone, or both in combination on the tibial cartilage growth plate (CGP) width and tritiated thymidine uptake within the CGP was studied in hypophysectomized immature male rats. The effect on femur length was also evaluated. GH caused resumption of growth and widening of the CGP as well as increased thymidine uptake. E 2 depressed these effects in a dose-related manner. It is concluded that E 2 administration to immature rats accelerates epiphyseal maturation without simultaneously accelerating linear growth.

Lipid composition of Plasmodium knowlesi membranes: Comparison of parasites and microsomal subfractions with host Rhesus erythrocyte membranes☆

Abstract 1. 1. Plasmodium knowlesi has significantly more phospholipid and less cholesterol (phospholipid: cholesterol ratio = 5·2) than the host erythrocyte membranes of the Rhesus monkey (phospholipid: cholesterol ratio = 2·15). 2. 2. Although both parasite and host red cell have the same major phospholipid components (phosphatidylcholine and phosphatidylethanolamine), other phospholipids differ significantly. 3. 3. The red cell contains 12–14 per cent sphingomyelin and 12 per cent phosphatidylserine, whereas the parasite contains only 2–3 per cent sphingomyelin, 8–10 per cent phosphatidylinositol, and barely detectable levels of phosphatidylserine.

Factors influencing intestinal cell renewal: A statement of principles

Intestinal cell renewal is influenced by a hierarchy of factors. The genetic apparatus of the individual cell constitutes the primary factor. Its phenotypic expression is under a cybernetic control which through coordinated enzyme induction or repression regulates the synthesis of the different constituents of the cell. Various endogenous and exogenous factors influence the rate and the direction of the metabolic sequences but do not affect the innate properties of the intestinal epithelial cell. The biochemical processes occur within a morphological framework. The anatomical organization of the intestinal mucosa prescribes the direction in which the biochemical processes can find expression. Despite considerable progress our knowledge of the interaction of the various factors which control cell renewal is still incomplete. When we obtain this knowledge we shall have made an important advance towards our understanding of how cancer develops in the intestines.

Changes of intestinal absorptive cells during maturation: An electron microscopic study of prenatal, postnatal, and adult guinea pig ileum

Maturation of intestinal epithelial cells in the distal ileum of the guinea pig is accompanied by an increase in length and number of microvilli of villus absorptive cells; in the three age groups studied microvilli reach their maximal length in the mid-villus area and become shorter at the villus tip, their width remaining essentially unchanged. Mitochondria of villus epithelial cells change their shape and size and increase in number with age. Prenatally they are large; two days after birth greatly increased numbers of small and large forms are present. Only large numbers of small forms are seen in the adult. In contrast crypt cell mitochondria are large at all stages. The complexity and numbers of cytoplasmic membrane systems increase with age and are modified by villus location. Monoparticulate glycogen deposits shift dramatically after birth and are absent in the adult. A correlation of structural changes to altered functional demands is attempted. It is suggested that the intraluminal intestinal environment exerts a morphogenic effect at the ultrastructural level.

CONSTITUTIONAL HYPERBILIRUBINEMIA WITH UNCONJUGATED BILIRUBIN IN THE SERUM AND PIGMENT DEPOSITION IN THE LIVER. REPORT OF A CASE.

SummaryA case of constitutional hyperbilirubinemia with mild elevations of un-conjugated bilirubin in the serum was reported which was further characterized by an accumulation of pigment granules in the liver cells of the Dubin-Johnson-Sprinz-Nelson type. Electron-microscopic studies demonstrated predominantly lipofuscin-like pigments in the liver cells. The pathogenesis of this condition and the chemical nature of these pigments were briefly discussed. Attention was called to a variant of the Gilbert-Meulengracht syndrome.

Chloroquine sensitivity and pigment formation in rodent malaria.

Summary The degree of selective uptake of chloroquine by P. berghei yoeli and P. berghei CR in the mouse is inversely related to the level of resistance demonstrable and does not depend on previous or concurrent exposure to the drug. Chloroquine sensitive P. berghei NYU-2 when passed into the rat, exhibits an increased tolerance to chloroquine, behaving in this respect like P. berghei yoeli in the mouse. However, it accumulates chloroquine-14C to an essentially identical degree as the same strain in the mouse, which is extremely sensitive to chloroquine. The decrease or disappearance of pigment in P. berghei NYU-2 when passed into the rat, ite growth in the presence of chloroquine and may not have any direct relationship to the mechanism(s) of resistance.