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Biomedical subjects

W H Niemann

Publications and source records attributed to W H Niemann.

At least 19 recordsLinked to original sources

C-type virus particles in placentas of rhesus monkeys after maternal treatment with recombinant leukocyte A interferon.

Interferon inhibits the normal replication of C-type virus particles grown in vitro. The ability of interferon to produce a similar effect in vivo was tested in rhesus monkey placentas which are known to contain C-type virus particles. Samples of placenta from 6 monkeys treated with recombinant leukocyte A interferon (25 x 10(6) units/kg) for 7 to 21 days and from 6 control monkeys were examined in the electron microscope. Budding and immature C-type virus particles were present in every placenta examined from both interferon-treated and control monkeys. Mature particles were found in placentas from 3 of 6 monkeys in both treated and control groups. Possible explanations for the absence of detectable effects of interferon in C-type virus particle formation in these placentas are unresponsiveness of the trophoblast to interferon or inadequate exposure time to interferon of placental sites from which C-type particles are produced.

Animals↗

Chronic instrumentation and longterm investigation in the fetal and maternal baboon: tether system, conditioning procedures and surgical techniques.

A tether system, conditioning procedures and surgical techniques were designed to maintain chronic catheters and electrodes in the pregnant baboon and her fetus. The tether system was comprised of a lightweight metal backpack containing catheters and electrodes, couplers, pressure transducers and electrical cabling. The backpack was held snugly in place by shoulder and body straps. A flexible metal tether connected the pack to a ball bearing assembly mounted on the top of the animal's home cage. Attached to the assembly were two infusion pumps, fluid reservoir and slip ring electrical connector. The entire system rotated freely with the movements of the animal; thus, the instrumentation and connectors were secure while access was maintained for continuous physiologic recording and intravascular infusion or intermittent blood sampling with minimal physical restraint. Animals were conditioned to accept the system prior to pregnancy and animals who demonstrated tolerance were bred. An initial group of 10 pregnant animals were sham tethered during pregnancy at 102 +/- 7 days with term gestation estimated at 180 days. Surgical procedures were done at 136 +/- 4 days with placement of catheters in the maternal femoral artery and vein, fetal carotid artery jugular vein and trachea, amniotic fluid cavity, and electrodes for fetal electrocardiogram and electroencephalogram. The mean fetal survival time was 9.3 (range 0 to 29) days. The major complications which led to early delivery were placental abruption and rupture of amniotic membranes. With ultrasonic localization of the placenta and determination of fetal position before surgery, these complications may be avoided.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Tubuloreticular inclusions in placental chorionic villi of rhesus monkeys after maternal treatment with interferon.

Tubuloreticular inclusions were observed in placental chorionic villi of rhesus monkeys after pregnant female monkeys were injected intramuscularly with recombinant leukocyte A interferon (25 X 10(6) units/kg). They were identified in endothelial cells, fibroblasts, and Hofbauer cells of the chorionic villi, providing evidence that interferon crossed at least part of the maternal-fetal partition. Induction of tubuloreticular inclusions in these cells by exogenous interferon has not been previously reported. Tightly packed regular tubular arrangements appeared in endothelial and Hofbauer cells and loosely organized tubular arrays in fibroblasts. The maximum dimension of the tubuloreticular inclusions measured 3 micron and the diameter of the tubules was 20 nm. The tubuloreticular inclusions were continuous with, and surrounded by, smooth endoplasmic reticulum that was often connected to rough endoplasmic reticulum. The tubuloreticular inclusions were not detected in placental chorionic villi from monkeys not treated with interferon or from interferon-treated monkeys 30 days after cessation of treatment. These results indicate that the formation of tubuloreticular inclusions in rhesus monkey placentas was a transient response associated with elevated serum levels of interferon.

Animals↗

Chemical and ultrastructural changes in tapetum of beagles with a hereditary abnormality.

We have defined the defect in the tapetum of beagles with an inherited tapetal abnormality to be the absence of both zinc and cysteine from the tapetal rods. This was demonstrated by direct measurement of zinc and cysteine and by histochemical localization of zinc. The latter method also indicated an interesting substructure in tapetal rods from normal beagles, in which the zinc is apparently distributed in two concentric rings. The chemical changes involved in different methods of fixing this unique tissue have been examined and correlated with the ultrastructure.

Animals↗

Effects of endotoxin on the pregnant baboon and fetus.

Effects of E. coli endotoxin upon uterine activity and maternal and fetal condition were studied in four pregnant baboons and their fetuses. Uterine activity increased significantly following administration of endotoxin to the mother. Endotoxin also produced maternal circulatory collapse, severe acidosis, and profound fetal asphyxia resulting in death. Death also occurred in three of the four mothers within 24 hours without amelioration of their conditions.

Acidosis↗

Temperature gradient between fetus and mother as an index for assessing intrauterine fetal condition.

Temperature gradient between fetus and mother (deltaTF-M) was measured in 29 pregnant baboons. Thermocouples were implanted in the fetal esophagus and the maternal colon, and, in some instances, thermistor probes were also placed in the fetal esophagus, scalp, and shoulder muscle. Under steady-state conditions, the fetal temperature was found to be higher than that of the mother. Temperatures in the fetal esophagus, scalp, and shoulder were 0.47, 0.28, and 0.19 degrees C. respectively, higher than those in the maternal colon. There was an increase in deltaTF-M during acute fetal stress induced by asphyxia, secondary to occlusion of the umbilical cord, maternal aorta, or inferior vena cava, or to acutely increased uterine activity. This increase in deltaTF-M most likely reflects impairment of heat dissipation from the fetus to the maternal compartment. A decreased deltaTF-M was observed when the stress on the fetus was subacute and prolonged. This is probably the result of a diminution of heat production by the fetus as the metabolic rate is lowered during prolonged hypoxia. Ten to 30 minutes after the cessation of vital signs of the fetus, the deltaTF-M became zero.

Acute Disease↗

Umbilical vein occlusion and transient acceleration of the fetal heart rate. Experimental observations in subhuman primates.

Transient acceleration of the fetal heart rate is commonly seen in the cardiotachometer tracing of the human fetus during labor. A likely cause appeared to be partial occlusion of the umbilical cord. On the basis of this hypothesis, fetal cardiovascular responses to partial occlusion of the umbilical cord or isolated intra-abdominal portion of umbilical vein were studied in near-term pregnant baboons and rhesus monkeys prior to and following sympathetic blockade with dibenzyline and propranolol. The responses were of two types. In the well-oxygenated fetus, partial occlusion resulted in transient acceleration of heart rate and a decrease in pulse pressure. This response was abolished with dibenzyline or propranolol. In the hypoxic fetus, partial occlusion resulted in either bradycardia and hypotension or hypotension with no alteration in heart rate. Thus, transient acceleration of the fetal heart rate can be explained on the basis of a sympathetic response to diminished venous return. It would appear to be an early sign of a potential cord complication. This response will not be seen if the fetus becomes asphyxiated and hypoxic.

Animals↗

Chenodeoxycholic acid induced liver injury in pregnant and neonatal baboons.

The prolonged feeding of chenodeoxycholic acid produces hepatic injury in both pregnant and non-pregnant baboons. CDC feeding does not adversely affect ovarina function and no teratogenic effects of this bile acid were noted in 16 live birth and two stillborn progeny of CDC fed animals. However, 10 of the 16 live birth neonates and one stillborn had focal hepatic lesions histologically similar to those observed in the adult animals. In addition one neonate had gross hepatic necrosis. The severity of the liver damage was related to the content of lithocholic acid in the bile of both the neonates and their mothers. Experiments with 14C-chenodeoxycholic and 14C-lithocholic acid demonstrate that the lithocholate in the enterohepatic circulation of the neonate is derived from the CDC fed to the pregnant adult. In the gallbladder bile of the neonate most, but not all, of the lithocholate is conjugated but unsulfated. Both newborn and adult baboons sulfate lithocholic acid but to an extent less than that reported for man. Less efficient sulfation of lithocholic acid in the baboon may exaggerate the toxicity of CDC feeding in this species compared to man. Nevertheless, the potential for adverse effects on the fetal liver must be recognized as a risk associated with the use of chenodeoxycholic acid in women of child-bearing age.

Animals↗

Diagnosis of pregnancy in chimpanzees using the nonhuman primate pregnancy test kit.

The usefulness of The Nonhuman Primate Pregnancy Test kit for diagnosis of pregnancy in chimpanzees was determined. This hemagglutination inhibition test for urinary chorionic gonadotropin accurately indicated conception by positive responses in 151 to 153 specimens collected between 20 and 133 days after the estimated day of fertilization. The rate of false positive responses did not exceed 1%.

Animals↗

Myocardial conduction defects in association with compression of the umbilical cord. Experimental observations on fetal baboons.

Experiments have been performed in 16 pregnant baboons to study in greater detail the fetal hemodynamics, heart rate, and acid-base changes during occlusion of the umbilical cord. A total of 32 observations were made during which the umbilical cord was completely occluded with the fetus intact in utero; 11 were made after the intravenous administration of atropine, 0.01 to 0.02 mg. per kilogram, to fetus. Various degrees of conduction defects occurred in 17 of 21 observations before atropine. Complete atrioventricular block with extrasystoles was seen six times. Upon release of cord occlusion, there was a rapid recovery of myocardial conduction. Atropine prevented myocardial conduction defects; bradycardia was less and the onset was delayed. These observations suggest that myocardial conduction defects which occur during the course of cord occlusion are due to parasynpathetic stimulation. They could also be due to an increased sensitivity of the fetal myocardium to acetylcholine under hypoxic conditions. No recommendation can be made at the present time with regard to the administration of atropine to the fetus when cord compression is suspected on clinical grounds.

Acid-Base Equilibrium↗

Increased uterine activity and fetal deterioration during maternal hyperthermia.

The role of hyperthermia in the absence of infection has been investigated in the pregnant baboon. Twenty-three near term animals were used. Catheters were placed in maternal and fetal arteries and thermocouples implanted in maternal colon and fetal esophagus. Maternal temperature was raised to between 41 and 42 degrees Centigrade (C.), by applying external heat. The temperature gradient between fetus and mother (delta T F-M) was 0.47 degree C. under steady-state conditions with maternal temperature at 38 degrees C. and rose to 0.75 degree C. at 42 degrees C. Hyperthermia caused a twofold increase in uterine activity; a metabolic acidosis developed in the mother and a profound acidosis and hypoxia developed in the fetus. There was also a marked fall in blood pressure and an increase in heart rate in both mother and fetus; late deceleration of the fetal heart rate occurred at a higher oxygen level and pHa than has been observed under normothermic conditions.

Acidosis↗

Duration of chorionic gonadotropin production by the placenta of the rhesus monkey.

Concentrations of macaque chorionic gonadotropin (mCG) in placenta, blood and urine of rhesus monkeys have been measured by both radioimmunoassay and bioassay throughout gestation. mCG was easily detected and quantified in these specimens for a brief period in early pregnancy, but was not detectable between the 40th day of pregnancy and term in placental extracts, serum, or 40-fold urine concentrates. The apparent absence of mCG after the 40th day of pregnancy makes these macaques a valuable model for pregnancy research, where the absence of chorionic gonadotropin is experimentally desirable. Unlike women and some higher primates, the functional status of the fetal, placental and maternal endocrine compartments of macaques can be studied in the absence of circulating chorionic gonadotropin during mid and late gestation.

Animals↗

Effect of aminoglutethimide on serum progesterone and estrogen in the pregnant baboon (Papio SP).

AG was administered orally twice daily for 1 or 3 days to six baboons whose duration of pregnancy ranged from 31 to 99 days. Serum progesterone levels were reduced to as little as 3.2% of the initial concentration in one animal and to 20% or less in four of the five remaining baboons. Serum estrogen levels were depressed by 50% or more in three of the four animals in which they were measured. However, pregnancy ensued for at least 3 wk after treatment in all animals. The data suggest that peripheral blood levels of sex steroids may not reflect the critical concentration of hormones required at the uteroplacental juncture for the successful pregnancy maintenance.

Abortion, Spontaneous↗

Application of the Subhuman Primate Pregnancy Test kit to pregnancy diagnosis in baboons.

The Subhuman Primate Pregnancy Test kit was used for diagnosis of pregnancy in 15 baboons. This hemagglutination inhibition test for urinary chorionic gonadotropin accurately indicated conception by positive responses in 106 of 109 specimens collected between 17 and 30 da after the estimated day of fertilization. Maximum hormone levels were reached during the middle of this 14-da interval. The rate of false positive and false negative results did not exceed 1%.

Animals↗