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Biomedical subjects

P Kaufmann

Publications and source records attributed to P Kaufmann.

At least 163 records · Page 9Linked to original sources

The development of the human placental villous tree.

The present investigation was undertaken in order to achieve a better understanding of the dynamics of placental villous differentiation. Villous trees from human placentas from different stages of pregnancy (first trimester to full term) were isolated and studied by light microscopy and scanning electron microscopy. For light microscopy the trees were serially sectioned and two-dimensionally reconstructed. For scanning electron microscopy complete villous trees or freeze-cracked villi were studied. The most important finding was that the mesenchymal villi are continuously newly formed out of the trophoblastic sprouts throughout pregnancy. Because of this they exist in all stages of pregnancy and have to be considered the basis for growth and differentiation of the villous trees. In the first two trimesters they are the forerunners of the immature intermediate villi, whereas in the last trimester the mesenchymal villi are transformed into mature intermediate villi. The immature intermediate villi formed during the first two trimesters are developmental steps towards the stem villi. On the other hand, the mature intermediate villi, which only are developed during the last trimester, produce numerous terminal villi. The latter are not active outgrowths caused by proliferation of the trophoblast, but rather passive protrusions induced by capillary coiling due to excessive longitudinal growth of the fetal capillaries within the mature intermediate villi.

Cell Differentiation↗

Extracellular matrix influences hormone and protein production by human chorionic villi.

Increasing evidence confirms that the extracellular matrix greatly influences cell behaviour and function. Collagen and fibrin are in contact with trophoblast throughout pregnancy. To investigate whether these two matrices influence hormone production by the trophoblast, explants from first-trimester chorionic villi were cultured for up to 30 days either a) in medium with agitation, b) embedded in type-I collagen (three-dimensional gels), or c) embedded in fibrin (three-dimensional gels). The supernatant culture medium was changed every 48 h and tested by radioimmunoassay for hCG, progesterone and pregnancy-associated plasma protein A. In addition, after 3, 7, 15, and 30 days of culture villi were fixed and studied by light and electron microscopy. Embedding in the extracellular matrix showed higher and longer-lasting production rates of all measured products and superior structural preservation as compared to cultures with agitation. Collagen matrix proved to be superior to fibrin. As established by several tests, this difference was neither due to thrombin used to polymerize fibrinogen, nor to differences in the diffusion rates through the two different matrices used. We conclude that extracellular matrix, particularly collagen, influences the synthesis of trophoblastic products. Embedding of the villous explants in three-dimensional gels constitutes a new method for long-term cultures of chorionic villi.

Chorionic Gonadotropin↗

The influence of hypoxic cell-free perfusion and ischemia on cell morphology in the proximal tubular S2-segment of the rat kidney.

In the present study, in-situ perfused rat kidneys were used as a model to demonstrate the different morphological changes induced by various periods of warm ischemia or of warm hypoxic cell-free perfusion. Light and electron microscopic evaluation revealed no changes in the S2 proximal tubular cells after short exposure times of up to 4 min, whereas longer periods resulted in changes ranging from slight alterations (at 10 min) to severe damage (at 60 min). Warm hypoxic cell-free perfusion induced obvious alterations in the proximal tubular cells somewhat sooner than warm ischemia. The microscopical findings were consistent with the statistics of a detailed morphometrical analysis performed on the mitochondrial diameter. The results were further substantiated by counting intramitochondrial electron-dense condensations ('flocculent densities') as indicators of irreversible cell alteration.

Animals↗

The results of treatment of gunshot wounds to the brain in children.

Thirty-three children ranging in age from 8 months to 15 years were treated for gunshot wounds to the brain. Half of the children were less than 10 years old. Fifty-eight percent died. Mortality was influenced by the trajectory of the bullet, intent to commit suicide, and the neurological status immediately after injury. The age and sex of the child and the caliber of the bullet did not influence survival. Three-fourths of the deaths occurred within 24 hours of injury, suggesting these patients had a mortal wound from the onset. Eleven of the children were attempting suicide, 9 of whom died; 13 were playing with a gun, 5 of whom died; 2 were shot as innocent bystanders to crimes in progress; 1 was shot while involved in a criminal act; 1 was shot in a hunting accident; and in 2 who died within minutes of arrival, the circumstances of the shooting were not documented. Of the survivors, none was left vegetative after 6 months, 3 had severe disabilities, 9 were moderately disabled, and 2 had a good outcome. The mortality rate is strikingly similar to that of adults with similar injuries; however, the morbidity appears to be less. On the other hand, with simple preventative measures, virtually each injury would have been avoided.

Accidents↗

Fetal vasculogenesis and angiogenesis in human placental villi.

Placental villi of 5 exactly defined early human specimens ranging from day 21 post conception (p.c.) until day 42 p.c. and from an additional 43 specimens from about 5 to 40 weeks menstrual age have been analyzed ultrastructurally with regard to fetal vasculogenesis and angiogenesis. The following results were obtained: The first cells differentiating at day 21 p.c., probably originating from mesenchymal precursors, are macrophage-like cells. At almost the same time, mesenchymal cells transform into haemangioblastic cell cords which are the forerunners of the capillary endothelium and haematopoietic stem cells. A third cell population related to the fetal circulatory system and derived from the mesenchymal cells are presumptive pericytes. Capillary formation takes place by the aggregation of haemangioblastic cells which are attached to each other by intercellular junctions. The lumen is formed by the dehiscence of the intercellular clefts. A capillary basal lamina cannot be detected earlier than in the last trimester. In this last period of gestation, fetal villous angiogenesis takes place by the proliferation of the existing endothelium and pericytes rather than via haemangioblastic cells.

Blood Vessels↗

Localization of substance P-like immunoreactive fibers in the thoracic spinal cord of guinea pig.

A dorsal-horn fiber system is revealed in the thoracic spinal cord of guinea pig by means of substance P immunocytochemistry. This system has repeated craniocaudal and/or caudo-cranial extensions and possesses five main components: a superficial network, situated beneath the dorsolateral surface of the spinal cord. This network is connected with the dorsal root fibers and the accumulations of substance P-like immunoreactive (SP-LI) fibers in the Lissauer's tract; an accumulation of SP-LI fibers in the Lissauer's tract at the border of the dorsal horn; two collateral SP-LI fascicles (one lateral and one medial) emerging from the SP-LI fiber accumulation in the Lissauer's tract; a transversal fascicle running through laminae III-V, and an SP-LI network in the region of the lateral spinal cord nucleus. These components of the dorsal-horn fiber system show widespread connections with ipsi- and contralateral spinal cord areas, connecting them in cranio-caudal and/or caudo-cranial directions. The SP-LI dorsal-horn system has close relationship with groups of preganglionic sympathetic cells in the intermediate zone of the spinal cord, respective with the vegetative network of this zone. It is suggested that some fibers of the dorsal-horn system that originate from dorsal-root ganglia may represent primary sensory or visceral afferents. It is likely that the dorsal-horn fiber system and the vegetative network of the thoracic spinal cord may represent the morphological basis for the integration of the central and peripheral vegetative nervous systems, and the somatic and vegetative nervous system.

Animals↗

Morphology of placental villi after premature delivery and its clinical relevance.

Based on a new concept of maturation of the placental villous tree and its disorders (synchronous and asynchronous immaturity, asynchronous maturity, hypermaturity, and terminal villi deficiency) we studied the possible effect of the placental villous tree on the premature onset of labour. In mature normal neonates irregular and asynchronous villous patterns were found in 50% of cases. In prematurely delivered neonates, only 33% of the corresponding placentas show synchronous immature villous patterns. Uterine bleeding in the first trimester was associated with a 42% of incidence of premature maturation of the villous tree. These findings strengthen the idea that hormonal imbalance in early pregnancy influenced villous development. In "prematurity without recognizable cause" there was a higher percentage of villous maldevelopment (33%) than that previously described in the literature. In severe pre-eclampsia combined with premature onset of labour, 60% of our cases showed hypermaturity of the villous trees. Synchronous immaturity was reduced to 15%. We conclude, that even a rather rough definition of the histological features of placental villi is sufficient to produce numerous correlations between clinical events preceding premature delivery and placental structure. So the influence of placenta on the premature onset of labour needs more attention.

Chorionic Villi↗

The fetal vascularisation of term human placental villi. II. Intermediate and terminal villi.

Vessel arrangement and vessel structure of the intermediate and terminal villi of 50 human normal term placentas have been studied by means of semithin histology, three-dimensional reconstruction of serial sections as well as scanning electron microscopy of vessel casts. The reliability of the methods applied has been checked by a morphometrical comparison of the luminal diameters obtained. The mature intermediate villi are characterized by the presence of 1 to 2 terminal arterioles as well as 1 to 2 postcapillary venules, and a few moderately coiled, mostly narrow capillaries, some of which belong to the so-called paravascular network. The remaining capillaries are continuous with the capillary loops of the terminal villi. The fetal vessels of the terminal villi are represented by capillary loops only, parts of which are sinusoidally dilated, reaching diameters up to 50 micrometers. Depending on the method, the mean vessel diameter of the terminal villi is 12.3 (vessel casts) or 14.5 micrometers (semithin sections). The capillaries of the terminal villi are arranged in such a way that 3 to 5 terminal villi are supplied by the same, multiply coiled capillary loop. The average capillary length of the paravascular net is 1,000 to 2,000 micrometers, that of the terminal villus capillary loops 3,000 to 5,000 micrometers. The extent of sinusoidal dilation rises with increasing capillary length, indicating that the main functional importance of the sinusoids is the reduction of blood flow resistance.

Blood Vessels↗

The structure of the tupaia placenta. I. Histology and vascularisation.

The placenta of the tupaia is bidiscoidal, labyrinthine and endotheliochorial in structure. The two placental discs show a characteristic partition into three broadly fusing main lobules on the mesometrial, and some very small accessory lobules on the antimesometrial side. The accessory lobules are separated incompletely from each other. Their inner lobular structure is rather homogeneous. All vessels seem to exhibit a rather random distribution. The maternal vessels of the three main lobules are regularly arranged in such a way that each lobule can be subdivided into three zones. The lobular centre is the maternal inflow area. The intermediate zone surrounding the centre is composed of maternal and fetal capillaries; the peripheral capsule collects the maternal blood into coarse networks of veins. Each lobule corresponds to one maternal circulatory unit in which up to ten fetal circulatory units are included. The fetal vertical lobular arteries are evenly distributed. Fine networks of fetal capillaries spread out centrifugally towards small collecting veins. Opposite the maternal veins the fetal ones do not form meshworks. Within the main lobules fetal and maternal capillaries are arranged parallel, antiparallel or in varying angles to each other, resulting in a complex crosscurrent flow system.

Animals↗

The structure of the tupaia placenta. II. Ultrastructure.

Both placental discs of the tupaia placenta consist of three large mesometrial and numerous additional smaller antimesometrial lobules. The larger lobules can be subdivided into a central (maternal arterial inflow), intermediate (maternal capillaries, exchange area), and a peripheral zone (maternal veins). The ultrastructure of the intermediate lobular zone has been studied from day 21 until day 41 of pregnancy. The materno-fetal barrier is endotheliochorial in structure. The voluminous maternal endothelium is highly differentiated. The adjacent basement membrane, separating endothelium and trophoblast, is constantly interrupted by endothelial and trophoblastic extensions, forming intense interdigitations between both tissue layers. The trophoblast is a multinuclear continuous layer, syncytial or plasmodial in nature. Cytotrophoblast is missing in all stages studied so far. Towards term, the trophoblast differentiates into three distinct types, arranged beneath each other in a mosaic-type pattern: trophoblast with rough e.r. and trophoblast with smooth e.r. as dominating organelles, as well as thin trophoblastic lamellae, almost devoid of organelles. The connective tissue is composed of very compact, epithelium-like cells, whereas connective tissue fibres and interstitial space are virtually absent. Macrophages, undifferentiated fibroblasts and highly differentiated fibroblasts can be observed. There are structural transitions between connective tissue and neighbouring fetal capillary endothelium.

Animals↗

The fetal vascularisation of term human placental villi. I. Peripheral stem villi.

The fetal vascularisation of the most peripheral three generations of stem villi has been studied by means of semithin serial sectioning and scanning electron microscopy of vessel casts in 50 human term placentas. The vessel types have been classified according to the structure of the vessel walls. Stem villi with a diameter of 200-400 microns are characterized by one smaller artery and one small vein, some arterioles and venules and capillaries of the paravascular net. Stem villi of about 150 microns diameter contain arterioles and muscular venules besides the paravascular capillary network. The last generation of stem villi measuring 80 to 100 microns in diameter exhibit a terminal arteriole and a collecting venule as well as up to ten paravascular capillaries. The luminal width of the arterial and venous stem vessels is considerably smaller than described for other vascular beds. This may partly be due to postpartal vascoconstriction. The capillaries of the paravascular net normally to not show sinusoidal dilation. They are arranged as long, hairpin-like, poorly branched loops connecting the arterial and venous stem vessels to each other.

Arteries↗

Interaction of dietary fat and route of carcinogen administration on 1,2-dimethylhydrazine-induced colon tumorigenesis in rats.

Since the results of an earlier study indicating no effect of dietary fat on dimethylhydrazine (DMH)-induced colon cancer in rats differed from those of other investigators, the present study was initiated to determine if the modulating effect of fat intake on colon tumorigenesis was dependent on the route of DMH administration. Male weanling Sprague-Dawley rats (160) were fed one of two nutritionally balanced diets containing 5% or 24% corn oil (CO). Following 3 weeks adaptation to their respective diets, 40 rats from each diet group were treated with five doses of DMH (30 mg/kg) by intragastric (i.g.) gavage or subcutaneous (s.c.) injection, over a 3 week period. Rats were sacrificed when they showed clinical signs of colon tumor and surviving animals were killed 51 weeks after the initial DMH treatment. The cumulative probability of death with colon carcinoma did not differ between the dietary or treatment groups. There was no effect of route of administration or dietary fat on total intestinal tumor incidence. The number of rats with colon carcinoma was: 5% CO.IG = 25; 24% CO.IG = 27; 5% CO.SC = 23; 24% CO.SC = 19. Polypoid tumor incidence was significantly higher in the 24% CO.SC group (12/40) compared to the 5% CO.SC group (3/40) (Chi-squared = 5.25; p less than 0.03) while sessile tumor incidence was the inverse. Marginally significant differences in tumor morphology were noted between the IG groups.

1,2-Dimethylhydrazine↗

Scanning electron microscopy of stromal cells of human placental villi throughout pregnancy.

Morphological changes in fixed stromal cells and Hofbauer cells were studied throughout pregnancy in different types of placental chorionic villi by scanning electron microscopy. In the mesenchymal villus the fixed stromal cells were characterized by thin cytoplasmic processes. Hofbauer cells exhibited blebs on their surface. Large sail-like processes with a crescent profile which surrounded well developed stromal channels and a small cell body typified the small reticulum cells of the immature intermediate villus. The Hofbauer cells here displayed blebs, microplicae and large lamellipodia. Short cytoplasmic expansions and a large cell body characterized the fibroblasts present inside the stem villus. Hofbauer cells were rare, having blebs or a few short lamellipodia. The mature intermediate villus contained small and large reticulum cells. The latter had a much larger cell body than the small ones and displayed a few short cytoplasmic processes partly delimiting narrow incomplete stromal channels. Occasional Hofbauer cells with small microplicae and/or blebs were present. The small reticulum cells and fibroblasts present in the terminal villus showed similar morphological features as above. However, the former exhibited less developed cytoplasmic extensions and therefore no stromal channels were observed. In the terminal villus, the morphology of the rare Hofbauer cells was similar to that found in the mature intermediate villus.

Chorionic Villi↗

The stromal architecture of the immature intermediate villus of the human placenta. Functional and clinical implications.

Scanning electron microscopy of cryofractured immature intermediate villi showed numerous intercommunicating channels in the central region of the stroma, oriented mostly parallel to the major axis of the villus. In the stromal channels, numerous Hofbauer cells were present and their aspect and position inside the channels highly suggested a motility of these cells. These morphological data strongly support the fundamental role played by the immature intermediate villus in the normal and pathological development of the human placenta.

Cell Differentiation↗

Sequential changes in oligoclonal patterns during the course of multiple sclerosis.

The majority of patients with multiple sclerosis have an abnormality of their spinal fluid immunoglobulins. This alteration is manifested as patterns of diffuse protein bands in the gamma globulin region following electrophoresis. This pattern has been termed one of restricted heterogeneity, or an oligoclonal pattern. We have found changes in the banding pattern of some patients studied longitudinally. Since the significance of these findings may be relevant to the pathogenesis of this notoriously waxing and waning disease, we discuss the importance of methodologies as well as the concept that IgM and IgA may be relevant to the interpretation of these observations.

Electrophoresis, Polyacrylamide Gel↗