Responses of the uterine circulation to sympathetic nerve stimulation. Pregnant and non-pregnant sheep uteri were perfused in situ with arterial blood at a constant flow rate. Unilateral stimulation (1-2 ma, u ms pulse) of the distal end of the severed sympathetic chain (L3-L4) at frequencies between 5 and 25 Hz produced a graded increase in uterine artery pressure in both horns. At 25 Hz, pressure in the horn ipsilateral to the stimulated sympathetic chain increased by 28 +/  2% in four pregnant animals and 32 +/ 5% in six non-pregnant ewes. The response of the contralateral horn was significantly smaller than that of the ipsilateral horn (P less than or equal to 0.05). The response was alpha-mediated since it was abolished by local injection of dibenzyline into the middle uterine artery. The responses of the pregnant and non-pregnant animals were similar, indicating that pregnancy did not alter the alpha-adrenergic responses of the uterine vasculature.


Placental transfer of glucose.

Placental transfer of glucose. The rates of glucose transfer from maternal blood to pregnant uterus and from placenta to fetus were measured in eight sheep at spontaneously occurring glucose concentrations (control state) and while the fetus, the mother, or both were receiving a constant infusion of glucose. In addition two fetuses received insulin infusions. In the control state the net glucose flux from placenta to fetus was only 27 +/- 2.6% (SEM) of the net flux from the uterine circulation to the pregnant uterus. An empirical equation describing the relationship between placental glucose transfer and arterial plasma glucose concentrations was derived from the data and compared with equations constructed on the basis of methematical models of placental function. This analysis indicates that: (1) placental glucose transfer is mediated by carriers with Km approximately equal to 70 mg/dl; (2) the rate of glucose transfer from mother to fetus is limited primarily by the transport characteristics and glucose consumption rate of the placenta; (3) under normal conditions of placental perfusion, glucose transfer is approximately 15% less than it would be if placental blood flows were infinitely large.


Fuel metabolism in fasted newborn rabbits. Newborn rabbits delivered by Caesarean section at term were fasted for 72 h at 36 degrees C. Despite the abrupt interruption of maternal supply of energy substrates, glycaemia remains stable for 4 h after birth. This can be related to glucose production via rapid liver glycogenolysis; however, indirect evidence suggests that gluconeogenesis could also contribute to glucose production during this period. There is a selective decrease in the concentrations of gluconeogenic substrates and a suitable hormonal environment for gluconeogenesis as decreased insulin and increased glucagon concentration just after birth. The relative hypoglycaemia which develops after 6 h of life (2.6 mM at 72 h), despite high blood concentrations of non-esterified fatty acids and ketone bodies is not due to a deficient gluconeogenesis per se, as injection of gluconeogenic substrates to 72 h fasted newborns produces a three-fold increase in plasma glucose concentration. It is suggested that this relative hypoglycaemia is secondary to limited gluconeogenic substrate availability in the form of low circulting concentrations of gluconeogenic amino acids.


Effects of endogenous angiotensin II on the fetal circulation. The role of endogenous angiotensin II in the regulation of the circulation was investigated by infusion of [sar1],[ala8]-angiotensin II, a competitive antagonist of angiotensin II, into fetal sheep with chronically-maintained intravascular catheters. The thesis considered was that angiotensin II may have a greater role in the fetus than in the adult since the autonomic nervous system does not develop fully until late in gestation. Fetal cardiac output and its distribution to various organs and actual blood flows to fetal tissues were determined by the radionuclide-labelled microsphere technique. Intravenous infusion of [sar1], [ala8]-angiotensin II at a rate of 13.95-42.15 microgram/min per kg fetal body weight increased plasma renin activity from a control value of 8.9 +/- 1.6 to 18.9 +/- 3.9 ng/ml per h (SEM). Mean arterial blood pressure fell significantly from a control level of 47 +/- 1.6 to 41 +/- 1.1 mmHg. Blood flow to the unbilical-placental circulation decreased from 239 +/- 27.0 to 198 +/- 20.2 ml/min per kg, but the calculated vascular resistance in the umbilical-placental circulation did not change. Although cardiac output did not change, blood flow to the peripheral circulation, which includes the fetal skin, muscle and and bone and constitutes 75 +/- 0.9% of the total fetal body weight, increased as did flow to the thyroid and adrenal circulations. Endogenous angiotensin II appears to be important in maintaining blood flow to the umbilical-placental circulation by maintaining fetal arterial blood pressure. Angiotensin II exerts this effect by mediating a tonic vasoconstriction primarily in the peripheral circulation.


The postnatal development of the main olfactory bulb of the rat. The postnatal development from birth to 1 year of the main olfactory bulb was examined quantitatively. The volume of the main olfactory bulb increased over seven-fold by day 30 and remained unchanged thereafter. During the same period the volume of the granular layer increased 18-fold and the mean areas of the olfactory glomeruli increased seven-fold. The mean areas of mitral cell perikarya doubled between the neonatal and juvenile periods. The total number of the mitral cells, however, declined during the first three postnatal weeks. In the internal granular layer of the main olfactory bulb, 89% of the granule cells were acquired postnatally. Much of the cellular gain occurred during the first 3 weeks, with the period of maximum acquisition between days 8 and 14. The number of subependymal cells, the precursors of granule cells, reached a peak at 12 days and gradually declined. But some primitive cells could still be found at one year of age and there was an increase in the total number of granule cells beyond day 30. The mean nuber of internal granular layer cells in a single main olfactory bulb of adult rats was about 5 X 10(6); the number of mitral cells about 4 X 10(4). In the animals injected with 3H-thymidine on day 20 and killed 2 h after injection a small but significant proportion of cells was labelled in the subependymal layer but few in the internal granular layer. In the animals killed 20 and 40 days after injection there was a 10--11-fold rise in the proportion of labelled internal granular layer cells. The proportion of labelled internal granular layer cells decreased in longer survival groups but the total number of labelled cells remained the same, even in year-old animals. However, the total number of internal granular layer cells in the sections examined increased with age.


Consumption of carbohydrates, amino acids and oxygen across the intestinal circulation in the fetal sheep. Since large volumes of nutrient rich amniotic fluid are swallowed by the fetus, it has been suggested that intestinal digestion and absorption contribute significantly to fetal nutrition. To see if nutrients are being gained across the intestine, we measured blood flow and intestinal arteriovenous concentration differences of glucose, alpha-amino nitrogen, lactate, fructose and oxygen in eleven third trimester fetal sheep with chronically implanted vascular catheters. We found that in fetal blood circulating through the intestine nutrient concentration decreased significantly with arterio-venous concentration differences for glucose of 0.78 +/- 0.21 (SEM) mg/dl (P < 0.002), for alpha-amino nitrogen of 0.52 +/- 0.15 mg/dl (P < 0.005), for lactate of 0.68 +/- 0.24 mg/dl (P < 0.05) and for oxygen of 1.50 +/- 0.08 ml/dl (P < 0.001). Fructose concentration did not change. Blood flow to the fetal intestine averaged 89.92 +/- 7.16 ml/min and the intestine consumed 0.74 +/- 0.24 mg of glucose, 0.43 +/- 0.17 mg of alpha-amino nitrogen, 0.83 +/- 0.28 mg of lactate and 1.37 +/- 0.14 ml of oxygen per minute. Compared to previously published values for the umbilical uptake of nutrients the fetal intestine metabolizes about 4% of the glucose, 6% of the alpha-amino nitrogen, 13% of the lactate and 6% of the oxygen obtained across the umbilical circulation. Intestinal absorption does not appear to serve as a source of simple nutrients for the rest of the fetus, in fact intestinal metabolism extracts significant amounts of nutrients from fetal blood.


Glucose transfer across the intact guinea-pig placenta. Experiments were carried out in anaesthetized pregnant guinea-pigs. Following the maternal injection of a bolus containing 14C-hexose and 3H2O, blood was sampled from the fetal umbilical vein during a single circulatory transit. A placental transfer index was calculated from the ratio of the tracers in the fetal whole blood divided by that in maternal plasma. The transfer index for D-glucose, 0.66 +/- 0.03 (SEM), greatly exceeded that for L-glucose, 0.013 +/- 0.004. Elevation of the maternal plasma D-glucose concentration, with unlabelled D-glucose, resulted in saturation of D-glucose transfer with an apparent Km of 1.2 x 10(-2) mol/l mean maternal plasma D-glucose. Phlorizin at maternal plasma concentrations of approximately 10(-3) mol/l inhibited D-glucose transfer by 40%. Phloretin did not affect D-glucose transfer at levels estimated to be 10(-4) mol/l. Specificity studies with substituted D-glucose analogues showed that alpha-methyl-D-glucoside is not transported by a facilitated pathway; 2-deoxy-D-glucose and 3-O-methyl-D-glucose share the D-glucose carrier and D-galactose has a partial affinity for the D-glucose carrier.


Placental transfer of dexamethasone in near-term sheep. The placental transfer of 3H-dexamethasone was studied in six near-term sheep. The placental clearance of 3H-dexamethasone was 18.8 +/- 3.5 ml/min per kg of fetal weight. The clearance of dexamethasone by the fetal tissues was 9.3 +/- w.5 ml/min per kg. The maximum placental clearance was 285 +/- 24 ml/min and the degree of diffusion limitation to the placental transfer of dexamethasone was 78 +/- 4%. The placental transfer of dexamethasone is therefore limited primarily by the nature of the placental barrier.


Demonstration of a quiescent period for feeding controls in the developing rat. Feeding behaviour of rats during development was assessed by weighing pups before and after a 4 h feeding session. During the first postnatal week, fasted pups gained significantly more weight than fed pups. This difference disappeared during the second week, but reappeared during the third week and persisted through the fourth week. In another series, pups were weighed at 2 and 4 h after beginning feeding. This showed that fasted pups aged 6 days compensate by suckling longer than fed pups. At 10 and 14 days of age there were no differences between fed and fasted pups at either 2 or 4 h, but from 16 days onward, fasted pups had eaten significantly more than fed pups at both times. A control experiment showed that the lack of compensation by fasted pups aged 10-14 days did not reflect lack of availability of milk. Video-analysis of suckling behaviour at ages 6, 10 and 15 days provided further evidence for lack of feeding controls during the second postnatal week: at 6 and 15 days fasted pups spent more time actively sucking than did fed pups. Whereas at 10 days, there were no differences between fed and fasted pups. It is concluded that feeding controls are present during the first postnatal week, become quiescent during the second week and reappear during the third week.


Stimulation of breathing movements in fetal sheep by inhibitors of prostaglandin synthesis. We studied the effects of inhibitors of prostaglandin synthesis on fetal breathing movements on 17 occasions in 11 lambs (gestational age 125-141 days). We gave 12 h infusions of sodium mechlofenamate (8.6-22.2 mg.kg-1) in 13 studies and indomethacin (21.8-38.8 mg.kg-1) in four studies. Results were similar with both agents and did not correlate with drug dosage. There were no changes in fetal arterial blood pressure, pH or blood gas tensions. We assessed fetal breathing movements by measurements of tracheal pressure for a control period of 224 h prior to and 208 h during the infusion of inhibitors of prostaglandin synthesis; their administration caused a marked stimulation of fetal breathing movements judged from the following four variables: (1) incidence of fetal breathing movements increased from 38.4 to 69.2% of the time (P < 0.001); (2) average amplitude of change in tracheal pressure during fetal breathing movements increased from 4.1 to 6.0 torr (P < 0.01); (3) maximal amplitude of change in tracheal pressure during fetal breathing movements increased from 8.8 to 13.4 torr (P < 0.01); and (4) the duration of the longest continuous episode of fetal breathing movements increased from 37 to 229 min (P < 0.05). Two fetuses had electrocorticogram (ECoG) recordings. In control periods, fetal breathing movements occurred only during low voltage, high frequency ECoG activity; however, during infusions of inhibitors of prostaglandin synthesis, fetal breathing movements occurred also during high voltage, low frequency ECoG activity. We conclude that inhibitors of prostaglandin synthesis stimulate fetal breathing movement in fetal sheep. These results suggest that a component of the prostaglandin system is a factor which inhibits breathing movements during fetal life.


Surgery of coexisting biliary malformations in choledochal cyst. Five of 13 infants and children with a choledochal cyst had coexisting biliary malformations. The specific lesions were main hepatic duct cyst (2), common hepatic duct stenosis (1), left hepatic duct stenosis (1), and Caroli's disease (1). The malformations were corrected or partially corrected at the time of operative resection of the cyst. The lateral portion of either or both of the major hepatic ducts was incised to the liver hilus thereby dividing areas of stenosis or laying open cystic malformations. Biliary reconstruction was by Roux-en-Y jejunostomy to the fileted common hepatic bile duct. The opportunity to correct coexisting biliary malformations is another advantage of total excision of choledochal cysts.


The surgical management of the unusual forms of biliary atresia. Of 50 infants undergoing laparotomy for biliary atresia during the last 9 yr at the Kobe Children's Hospital, 9 had variant forms, including (A) a gallbladder with a demonstrable connection with the intrahepatic biliary system, (B) a gallbladder with a connection with the extrahepatic biliary system and duodenum, and (C) a grossly visible subhepatic cyst. Three patients with form A underwent cholecystoduodenostomy. All these patients died of cholangitis and hepatic failure within 2 mo after operation. Two patients with form B were successfully treated by hepatic portocholecystostomy without any episodes of cholangitis. Two of the patients with form C, occurring in 1970, underwent an anastomosis between the subhepatic cyst and the duodenum. There was no bile excretion in these patients. The other two patients were treated subsequently by hepatic portoenterostomy with complete excision of the subhepatic cyst and excellent bile excretion was obtained. Infants with forms A and C should be treated by hepatic portoenterostomy instead of a direct anastomosis between the dilated portion of the extrahepatic biliary system and the alimentary tract. For patients with form B, hepatic portocholecystostomy seems to be the most suitable procedure relative to the prevention of postoperative cholangitis, which is the most serious complications in infants obtaining successful bile excretion.


Posttraumatic Budd-Chiari syndrome with late reversibility of hepatic venous obstruction. A peritoneo-venous shunt was inserted in a 15-mo-old infant with Budd-Chiari syndrome following hepatic trauma. Ascites resolved and late renewed patency of the right hepatic vein was demonstrated.


Glucagon in experimental intussusception. A standard type of ileocolic intussusception was produced in 69 puppies and the effect of glucagon on the hydrostatic reduction of the intussusceptions evaluated in a prospective, double-blind study. The reductions were attempted at intervals varying from 18 to 60 hr following the production of the intussusceptions. The overall reduction rate was 70% and there was no statistical difference in this rate between the animals receiving glucagon and those receiving placebos. None of the gangrenous intussusceptions were reducible with the hydrostatic pressure technique, irrespective of whether glucagon was used or not. A further evaluation was made of those animals in whom successful reductions were accomplished by the hydrostatic pressure method. Glucagon did result in significantly easier reductions, and an earlier return of normal vascular supply as measured by color and by arterial pulsations as compared to the control group.


Normal intestinal rotation with non-fixation: a cause of chronic abdominal pain. The majority of clinically significant gastrointestinal rotational anomalies involve:(1) an arrest of rotation about the superior mesenteric vessels, (2) abnormal peritoneal bands, and (3) obstruction with or without volvulus. Between 1973 and 1978, six children had chronic intermittent volvulus secondary to a nonfixed but normally-rotated intestine; this is 10% of all infants and children treated for malrotation in our hospital during the same period. Barium studies showed normal duodenojejunal configuration and a colon that was normally situated on at least one study. All were labeled as functional complainers by their pediatricians. One died of a volvulus because her complaints were appreciated too late. At laparotomy, evidence of chronic intermittent volulus secondary to nonfixation from the ligament of Treitz to the transverse colon was found in all patients. A Ladd procedure with appendectomy was performed and immediate resolution of symptoms was noted in each surviving child. Children with a story of chronic abdominal pain deserve a carefully interpreted history and radiographic examination before being labeled as chronic complainers.


An evaluation of the modified endorectal procedure for Hirschsprung's disease. During the past 4 yr, 60 patients with Hirschsprung's disease have been treated at our institution. Twenty-eight patients within this group have undergone a modified endorectal pull-through procedure. There are 18 males and 10 females in the series. There are 5 children with total colonic involvement, 3 patients with aganglionosis to the mid-transverse colon, and one child with Hirschsprung's disease extending to the distal jejunum. The associated anomalies have consisted of four cases of Down's syndrome, one of whom also has transposition of the great vessels. There has been no operative-related mortality or late mortality in our series. Two major complications (anastomotic leak following a colostomy closure and incorrect pathological diagnosis of aganglionic level) and five minor complications have occurred. The average follow-up period is 31.3 mo. The functional results postoperatively have been excellent. The 18 patients over the age of 3 yr are completely toilet-trained. The remaining patients are too young to be toilet-trained, but are continent in the sense that they do not soil between bowel movements. Because of the satisfying functional results in this series, we have now expanded our indications for this procedure to patients requiring total colectomy for ulcerative colitis and familial polyposis. During the past 2 yr, 8 patients with ulcerative colitis have undergone the endorectal pull-through together with a total colectomy.


Hirschsprung's disease with skip area (segmental aganglionosis). Hirschsprung's disease is characterized by a single aganglionic segment of colon extending distally to the anal margin. Well documented reports of segmental aganglionosis have been rare. We report a case of segmental aganglionosis in which there were two distinct aganglionic segments resected. The entire transverse colon between the two aganglionic segments was normally ganglionated, preserved, and utilized and functions in a normal fashion.


Acquired aganglionosis.

Acquired aganglionosis. A documented case of acquired aganglionosis is presented in which transrectal biopsies taken 4 mo apart first showed the presence then subsequently the absence of ganglion cells. Colostomy followed by a Soave procedure was curative.


Surgical treatment of thymic cysts and neoplasms in children. Based on experience with 17 patients and review of the literature, complete excision is possible for all benign thymic cysts and neoplasms. Recurrence is rare (2%). Most malignant thymomas in children are epithelial (73%). As with adults, prognosis depends on accurate surgical staging and aggressive surgical intervention. Even the largest tumors can be completely excised removing portions of lung, pleura, diaphragm, and pericardium in continuity as required. Cardiopulmonary bypass may be necessary when the innominate veins or the superior vena cava is involved. Irradiation is required for stage II and stage III lesions. Stage IV patients require irradiation and chemotherapy.


Abdominoscrotal hydrocele. Case presentation and review of the literature. Abdominoscrotal hydrocele has been known for over a century although it rarely has been reported in children. A review of the world literature revealed 84 such cases, only three cases in the pediatric age group. Our patient, a 5-mo old male, presented with abdominal and scrotal masses of 4 to 6 wk duration. The abdominal mass measured 12 x 8 cm. The scrotal mass, which clinically seemed to be a hydrocele, measured 3 x 5 cm. Both masses appeared cystic and communicated. Diagnostic work-up clearly established the diagnosis. Complete surgical excision was accomplished through an inguinal crease incision.


Meconium ileus: laparotomy without resection, anastomosis, or enterostomy. During the 14 yr from 1965 through 1978, 49 infants presented shortly after birth with intestinal obstruction due to impacted meconium. Three of these patients did not have fibrocystic disease. Eight patients were cured by a Gastrografin enema. There were 18 patients who had complications that included associated atresia, volvulus, and/or peritonitis. Various operations were done including resection with either primary anastomosis or enterostomy or varieties of the foregoing. Twenty-three babies had the simple uncomplicated form of meconium ileus. Eleven of these underwent resection and six patients died. Twelve patients were treated by laparotomy, ileotomy through a purse-string suture and prolonged irrigations using acetylcysteine. Of this group only one succumbed. This latter course of management is recommended for patients with simple uncomplicated meconium ileus as it involves no resection, no enterostomy, nor any primary anastomosis.


A perspective for pediatric surgeons: chronic idiopathic intestinal pseudoobstruction. Chronic idiopathic intestinal pseudoobstruction (CIIP) is a disorder of alimentary tract motility with onset of symptoms in adolescence or young adulthood, characterized by recurring attacks of abdominal pain, distention, vomiting, and constipation often leading to malnutrition and death. Starting with an adolescent patient, treated for a succession of life-threatening attacks of pseudoobstruction, the authors have identified CIIP in four generations of a Virginia family. Studies show characteristic dilation and diminished motility of the esophagus and intestine. Surgery's role in CIIP is palliative, and operation should only be offered when medical measures have failed to control symptoms.


Transcutaneous oxygen (tcPO2) measurements as an aid to fluid therapy in necrotizing enterocolitis. Impaired peripheral perfusion is a major problem in necrotizing enterocolitis with delayed recognition and definite documentation being primary factors. While blood pressure and other clinical measurements may improperly estimate the severity of the problem, changes in transcutaneous oxygen measurements and their relationship to arterial oxygen (the tcPO2/PaO2 ratio) potentially afford a sensitive measurement of peripheral perfusion. Experience in our unit confirms a close relationship between tcPO2/ and PaO2 being 0.97 +/- 0.04 (SE). Ten infants with birth weights of 640 to 1380 g, who subsequently developed necrotizing enterocolitis, had strikingly lower ratios initially (0.00, 0.00, 0.00, 0.17, 0.21, 0.43, 0.44, 0.48, and 0.56). Use of the tcPO2/PaO2 ratio to monitor fluid therapy was related to outcome, suggesting that this ratio is important in managing necrotizing enterocolitis.


Obstruction of the suprahepatic inferior vena cava as a complication of giant omphalocele repair. Obstruction of the inferior vena cava with resultant Budd-Chiari syndrome after giant omphalocele repair has not previously been reported. Such a case is presented. We hypothesize the mechanism of this blockage to be posterior displacement of the inferior vena cava during reduction of the viscera and closure of the anterior abdominal wall, thereby creating angulation and mechanical blockage of the inferior vena cava at the diaphragmatic hiatus.


The umbilical polyp.

The umbilical polyp. Anomalies of the omphalomesenteric duct (OMD) present a variety of surgical problems. The most readily apparent of these lesions is the umbilical polyp. One-third of patients explored at our hospital and 56% of patients reviewed had an additional OMD anomaly when explored for an umbilical polyp. The preferred treatment for this lesion should be a mini-laparotomy after the presence of intestinal mucosa at the umbilicus is confirmed.


The effects of intrapleural pressure on respiratory insufficiency. Newborns with congenital diaphragmatic hernia generally survive operative repair of the hernia but develop progressive respiratory insufficiency that proves fatal. One cause for the progressive respiratory insufficiency may be the overexpansion of the contralateral lung. It is postulated that the overexpansion occurs due to the empty space created by the lack of expansion of the hypoplastic lung on the side of the hernia. To test this theory, an animal experiment was devised to mimic the postoperative state in patients with diaphragmatic hernia. It was concluded that (1) A decrease in intrapleural pressure below normal in an empty hemithorax causes the opposite lung to overexpand into the empty hemithorax in neonatal Beagle puppies. (2) The overexpansion resulted in progressive respiratory insufficiency. (3) Increasing the intrapleural pressure by insufflation of air into the empty hemithorax stopped the overexpansion of the contralateral lung. (4) By not allowing the contralateral lung to overexpand, progressive respiratory insufficiency was prevented. (5) This may be a useful technique in neonates with congenital diaphragmatic hernia.


Respiratory paralysis to improve oxygenation and mortality in large newborn infants with respiratory distress. The nonsynchronous respiratory efforts of neonates with surgically correctable disorders may inhibit effective mechanical ventilation. The records of 25 infants treated with metocurine for muscular paralysis to improve mechanical ventilation were reviewed. All patients were greater than 35 (37.6 +/- 2.1) weeks gestation and 2.27 (2.98 +/- .47) kg. All required ventilatory support with an FiO2 of 100%. The mortality rate of this group of infants was 20% as compared with 73% (p < .001) in a similar group of 26 infants managed without paralysis. In 10 of the 25 infants treated with metocurine, pre- and 1 hr postparalysis paO2 values were available. The mean paO2 prior to paralysis was 62 (45--111) mm Hg and the mean post-paralysis paO2 was 144 (75--227) mm Hg, representing at 132% increase in paO2 (p < .001). The mean dosage for metocurine was 3.5 (1.45--6.79) mg/kg/day; however, those requiring paralysis for greater than 7 days showed a dramatically increasing requirement. These preliminary data suggest that respiratory paralysis reduces right-to-left shunting, improves paO2 and decreases mortality in large infants with severe respiratory distress requiring ventilatory support.


Transcutaneous oxygen monitoring in shock and resuscitation. Transcutaneous oxygen tension (TcPO2), arterial oxygen tension, pulse, blood pressure, cardiac output and base excess or deficit were serially measured in 18 piglets, 7 to 14 days of age, subjected to a 35% hemorrhage and reinfusion of shed blood. Eight of 18 pigs died. There is a strong correlation between TcPO2 and PaO2 during normal flow, but a marked discrepancy develops during hemorrhage. Cardiac output, base deficit, and TcPO2 all follow a similar pattern during hemorrhage, but TcPO2 decreases more rapidly and remains at a low level in the nonsurviving animals. TcPO2, therefore, appears to be a sensitive, noninvasive indicator of low flow and the adequacy of resuscitation.


Esophageal stenosis due to cartilaginous tracheobronchial remnants. In cases of congenital esophageal stenosis, tracheobronchial remnants in the distal esophagus should be considered a possible diagnosis. The cause is thought to be esophageal sequestration of a tracheobronchial anlage before embryologic separation. Primary resection of the stenotic portion of the esophagus with re-anastomosis is recommended. Such a case is reported.


The gracilis sling for fecal incontinence. During the past 20 yr, we have transplanted the gracilis muscle to the perianal position for use as a sphincter to achieve continence in 7 completely incontinent children, ages 7 to 16 yr. Complete continence was achieved in three, three were improved and one transplant became infected and failed completely. The procedure has been performed as originally described by Pickrell. The bowel must be impeccably clean prior to the operation and the muscle must be sutured as tightly as possible about the anus. These two details, in addition to postoperative training, are essential for a successful result.


An analysis of ultrasound scanning as a guide in determination of "high" or "low" imperforate anus. The classic upside-down abdominal roentgenogram and the use of pelvic reference points have frequently been inaccurate in assessing the level of the distal pouch in patients with imperforate anus. The ultrasonic study described is different from that previously reported and allows more precise localization of the distal rectal pouch. A review of our experience allows us to make certain definitive statements about this diagnostic modality.


Bile duct enlargement by infusion of L-proline: potential significance in biliary atresia. The normal signals of control of bile duct morphogenesis and growth are unknown. Consequently, aberrant development is poorly understood, as for example in those infants with biliary atresia or hypoplasia. A previous report by Isseroff et al., showed that a possible mechanism for the common bile duct enlargement by the parasite Fasciola hepatica was excess L-proline secreted by this parasite. This suggested to us that L-proline might be a specific growth factor for bile duct epithelium, and therefore possibly useful in the understanding and treatment of biliary maldevelopment. We now report an experimental study demonstrating the effect of L-proline on the normal biliary tree of the mouse. We also present a summary to date of an ongoing clinical restrospective study. These experimental findings suggest: (1) there may be a specific requirement for L-proline during the rapid growth of the biliary tract during neonatal life; (2) bile duct hypoplasia and atresia may result from a defect in proline metabolism; (3) proline administration during the early phase of biliary atresia may possibly be therapeutic.


Multiple genitourinary abnormalities in females with unilateral renal agenesis: three cases. We have the means to identify over 75% of infants and children with unilateral renal agenesis. It has been established that all patients with unilateral renal agenesis must be followed closely because of problems with the remaining kidney and other anomalies. It is apparent from embryologic studies and numerous reports that up to 89% of females with unilateral renal agenesis are likely to have significant accompanying genitourinary abnormalities. Most of these patients' genital problems occur at the time of puberty or pregnancy. Because of our experience with three teenage females who had unilateral renal agenesis and subsequent serious problems, we wish to advocate a prepubertal aggressive investigation.


Giant hydronephrosis in children.

Giant hydronephrosis in children. Twenty pediatric patients with giant hydronephrosis were reviewed. This was defined as a kidney that occupied a hemiabdomen, met or crossed the midline, and was at least 5 vertebrae in length. The majority (16) were cases with ureteropelvic junction obstruction. In 2 cases, the primary pathology was obstructive megaureter. In 2 cases, the infants had severe urethral valves with massive upper tract dilatation. In 6 patients with a normal contralateral kidney, nephrectomy was performed. In one patient with bilateral pathology, one nonfunctioning kidney was removed later. A reconstructive operation was undertaken in 14 of the 20 patients. There was one late death from septicemia in an infant male with urethral valves and bilateral dysplastic kidneys.


The characterisation of Fc receptors on cells from the metrial gland of the pregnant rat uterus. Using an EA rosetting technique on cells from the rat metrial gland at days 12--15 of pregnancy, approximately 30% of the cells were found to possess immunoglobulin (Fc) receptors. At dat 14 a comparison was made between cells from the metrial gland and cells from the peritoneal exudate; binding affinity of each for homologous and heterologous immunoglobulins was assessed by the resulting inhibition of rosette formation. Cells from the metrial gland were inhibited to a greater degree than cells from the peritoneal exudate by low concentrations of rabbit, human and rat immunoglobulin. The Fc receptors observed on cells from the metrial gland show some resemblance to those described by other workers on yolk sac cells and certain foetal placental cells, but their function is at present unknown.


Macrophage activity in mouse pregnancy.

Macrophage activity in mouse pregnancy. Antigen handling and clearance by macrophages during mouse pregnancy has been examined by monitoring blood levels of 125I-labelled polyvinyl pryrrolidone (PVP) at different times following its intravenous injection into mated females. PVP clearance is significantly reduced between days 12 and 14 of pregnancy in both syngeneic and allogeneic matings. No significant differences were observed between virgin and mated females at earlier or later states of pregnancy. The findings are discussed in relation to the possible role of macrophages in the immunoregulatory processes involved in the maintenance of the foetus as an intrauterine allograft.


Characterisation of the soluble fraction of human syncytiotrophoblast microvillous plasma membrane-associated proteins. Syncytiotrophoblast microvillous plasma membrane (StMPM) preparations were obtained from human full-term placentae by previously published methods of cold saline extraction and phase centrifugation. Purity of these preparations was assessed by electron microscopy, enzyme analysis and hydroxyproline content. IgG, albumin, alkaline phosphatase, transferrin, ferritin and alpha 2-macroglobulin were consistently detected in the aqueous soluble fraction from sodium deoxycholate-solubilised StMPM preparations by antigenic or electrophoretic analysis, beta 2-Microglobulin was not detected in these preparations. Up to 21 discrete protein bands could be demonstrated by SDS--PAGE, and their molecular weights determined. Many of these components need to be further identified, including a glycoprotein of molecular weight 36 500 which was particularly prominent. The soluble fraction from StMPM preparations gave a single strong precipitin reaction in immunodiffusion against wheat germ agglutinin, but not against other lectins studied.


Complement fixing activities of normal mammalian sera for homologous and heterologous sperm. The species of the natural anti-sperm antibodies found in normal mammals have been assessed using complement fixation tests. Heated rabbit sera showed complement fixing activity with both rabbit and guinea pig sperm, indicating that rabbit natural anti-sperm antibodies do not show clear cut species specificity in these interactions. On average, rabbit sera reacted more strongly with rabbit sperm that with guinea pig sperm but the difference fell short of statistical significance (P < 0.05) and there was considerable variation between sera in their anti-sperm activities. There were, however, clear species differences between rabbit and guinea pig sera in that heated guinea pig sera showed significantly weaker anti-sperm activity than heated rabbit sera (P < 0.005). Mouse vas sperm showed greater complement fixing activities (in combination with mouse serum) than did epididymal sperm (P = 0.05). These results are discussed in relation to possible functions of natural anti-sperm antibodies.


In vitro studies in reproductive immunology. - 2. Demonstration of the inhibitory effect of male genital tract constituents on PHA-stimulated mitogenesis and E-rosette formation of human lymphocytes. The effect of male genital tract components (human spermatozoa, intact and chromatographed seminal plasma fractions) on in vitro cell-mediated immune reactions was examined. Their addition to PHA-containing lymphocyte cultures resulted in a marked degree of inhibition of DNA synthesis, the response varying with the fractions employed. The interference by such components with a terminal cell event during blast transformation was suggested by the failure of stimulated cultures to incorporate thymidine irrespective of the time during the incubation period at which the constituents were added. Seminal plasma and sperm extracts were also shown to inhibit T-cell associated E-rosette formation. The inhibitory properties of genital fractions remained unaltered after repetitive freeze-thaw cycling when tested in the transformation and E-rosette assays. Heating to 100 degrees C modified the response with some of the fractions.


Specific assay for pregnancy-specific-beta 1-glycoprotein (Sp1-beta). Preparation of antiserum specific for SP1-beta by absorption with a crossreacting high molecular weight serum protein. Two pregnancy-associated proteins reacting with antibody against pregnancy-specific beta 1-glycoprotein (PS beta G or SP1) were separated by means of ammonium sulphate precipitation, size chromatography and preparative zone electrophoresis. The antibody preparation was made monospecific to the beta-mobile protein by liquid phase cross-absorption of anti-SP1 immunoglobulin preparation with the isolated alpha2-mobile high molecular weight protein. The specificity of the absorbed antibody was tested in line immunoelectrophoresis, rocket immunoelectrophoresis and crossed immunoelectrophoresis.


C1q-binding activity of serum from allogeneically and syngeneically pregnant mice. C1q-binding activity of serum during allogeneic and syngeneic pregnancy in mice was measured using the direct [125I]C1q-binding assay. In both strains there was an initial tendency for levels to rise in very early pregnancy (Days 2 and 4) followed by a progressive fall in C1q binding to a level significantly lower than that found in non-pregnant animals. The changes were present in both syngeneic and allogeneic pregnancies but the later changes were more pronounced in the latter. The presence of changes associated with syngeneic pregnancy suggests that these profiles are at least in part independent of genetic differences between mother and embryo.


Isolation of a human spermatozoal hapten "II2.2' and its reaction with naturally occurring human sperm-immobilizing sera from infertile patients. An extract of human spermatozoa was prepared using Hyamine 2389 and Triton X-100. With gel and ion-exchange chromatography several fractions were obtained of which are reacted specifically with sperm-immobilizing antibodies of infertile females and males in an immune inhibition test. This fraction showed haptenic properties, ahd a molecular weight of 1600 and was excluded as an anticomplement factor. After conjugation with cytochrome c the hapten II2.2 formed precipitation reactions with 3 out of 4 sperm-immobilizing sera. The titer reduction in sperm-immobilizing sera after adsorption with II2.2 may represent an in vitro model for a possible treatment of infertility in cases of a humoral sensitization against spermatozoa. On the other hand, the hapten might easily be synthesized and could, after conjugation to an appropriate carrier, serve as a contraceptive vaccine.


Immunological studies of the sperm-specific phosphoglycerate kinase-2 of mice. Antiserum was prepared to 500-fold purified PGK-2A from mouse testes. Depsite the apparent high purity of the immunizing antigen, double diffusion analyses showed two precipitin lines, one of which can be shown to correspond to PGK-2. An immunoabsorbent column of liver homogenate coupled to cyanogen bromid-activated Sepharose was used to remove the contaminating antibody. Both immuno-inactivation and double diffusion analyses demonstrated that the PGK-2 antigen appeared in testes between days 30 and 34 of postnatal development. The antisera prepared against highly purified PGK-2A did not disclose any immunological differences between PGK-2A, PGK-2B, and PGK-2C either by double diffusion analyses or quantitative immunoprecipitation. Antisera to PGK-2 did not inhibit in vitro fertilization of zona-free hamsters ova by mouse spermatozoa.


Resistance of female guinea pig fertility to efficient iso-immunization with spermatozoa autoantigens. Virgin female guinea pigs received two courses of immunization with S, P or T spermatozoa autoantigens and Freund's complete adjuvant and were mated from 1 up to 18 weeks after the end of each course. The immunizations were efficient as judged by the titers of circulating antibodies to S, P or T, the existence of antibodies to the corresponding immunizing antigen in cervico-vaginal secretions and by cutaneous reactions of delayed hypersensitivity. In spite of this successful immunization, the fertility rate was 100% after the first course and only slightly decreased after the second one. The only significant events were a delay in the time of fertilization and a high rate of intrauterine death (as already observed following anti-S immunization). The absence of fertility impairment was not due to a lack of a relevant antigen in the injected preparations since immunizing female guinea pigs with either epididymal spermatozoa or crude water-soluble extract also did not decrease the fertility. The mechanisms responsible for such a resistance remain to be elucidated; they may involve spermatozoa coating substances, enhancing antibodies or sperm immunosuppressive factors.


Immunogenicity of three C-terminal synthetic peptides of the beta subunit of human chorionic gonadotropin and properties of the antibodies raised against 45-amino acid C-terminal peptide. Immunological studies were carried out in rhesus monkeys and rabbits on three C-terminal synthetic peptides of beta-hCG (115-145; 111-145 and 101-145) after conjugating these to tetanus toxoid (TT). The immunogenicity of the peptide conjugates was comparatively poorer with reference to Pr-beta-hCG-TT conjugates at similar doses and immunization schedule. Amongst the three peptides, the best response was obtained with the 45-amino acid c-terminal peptide (45-CTP; 101-145). The anti-45-CTP recognized native hCG and was devoid of cross-reaction with hLH. hCG-induced testosterone production by mouse Leydig cells was inhibited by anti-45-CTP antiserum, although its neutralization capacity decreased more rapidly upon dilution than anti-beta-hCG sera of comparable titres. Immune complexes formed by the anti-45-CTP with hCG had a lower sedimentation value than those formed by anti-beta-hCG antisera with hCG, suggesting the presence of a limited number of immuno-determinant regions in the 45-amino acid C-terminal synthetic peptide.


Electrical stunning of Karakul lambs.

Electrical stunning of Karakul lambs. An apparatus designed to electrically stun Karakul lambs prior to slaughter was tested for efficiency using the cardiac pain reflex and electrocorticograms to assess unconsciousness. The electrical shock delivered by the apparatus was found to produce unconsciousness, as opposerd to curarisation, of sufficient duration to allow for subsequent slaughter.


Dislocation of the elbow and its social consequences for an African elephant. A dislocated elbow of a male elephant calf (Loxodonta africana) in the Addo Elephant National Park resulted in it being harassed by other elephants and consequently leaving its maternal herd at the age of 6 years, rather than the more usual age of 9-10 years. In the absence of large predators the elephant had survived for 9 years and had adapted its locomotion and intraspecific behaviour to its injury. The humeral joint of the affected forelimb was carried in partial extension while the cubital and carpal joints were permanently in partial flexion. Substantial secondary osteoarthritic changes, extensive fusion and compensatory remodelling of the humerus, radius and ulna had taken place together with compensatory development in the musculature. The planes of articulation of the limb bones had also been considerably rotated inward.


The seasonal incidence of helminth parasites of cattle in the Northern Transvaal Bushveld. During a period of 14 months two tracer calves per month were slaughtered after one month's exposure to natural helminth infestation on a farm in the Northern Transvaal Bushveld. Total parasitic helminth burdens, which were never large, were determined in order to define their seasonal incidence. The gastro-intestinal parasites that were recovered were Bunostomum phlebotomum, Cooperia pectinata, Cooperia punctata, Haemonchus placei, Oesophagostomum radiatum and Trichostongylus spp. Of these Cooperia spp. were most prevalent, and the highest mean monthly burden attained was 1250 in November, 1976. Worm burdens were apparently positively correlated with rainfall, which during the survey period was lower than the average for the particular region. In addition to the more common gastro-intestinal nematodes, Thelazia rhodesii and Parafilaria bovicola were also encountered. Various techniques employed in conducting helminth surveys are discussed.


Enzootic icterus--a form of chronic copper poisoning. The findings of a recent investigation into the epizootiology, course, symptomatology, gross pathology, chemical pathology and prevention of Enzootic Icterus are presented and the findings of previous investigations on these and other aspects are reevaluated. Enzootic Icterus and chronic copper poisoning are shown to be identical in all fundamental features. Both diseases are characterised by sudden onset, high mortality, icterus, anaemia, haemoglobinaemia, methaemoglobinaemia, haemoglobinuria and deeply pigmented kidneys. There are no described microscopic features on which the diseases can be differentiated. Very high levels of copper in the blood, liver and kidneys are found in both diseases. In the present work 36 liver specimens had a mean copper concentration of 701 microgram/g. Of 31 kidney specimens no values under 10 microgram/g were found while the mean was 107 microgram/g. Prevention of Enzootic Icterus by salts of molybdenum given orally confirms the identity. No close relationship with Geeldikkop is found other than the probability that the two diseases may act synergistically. Interpretation of existing knowledge of mineral levels of natural grazing in the enzootic region shows that the levels can account for the presence of chronic copper poisoning, although more investigation is required.


The anthelmintic efficacy of albendazole against gastrointestinal roundworms, tapeworms, lungworms and liverflukes in sheep. Anthelmintic trials were carried out to evaluate the efficacy of albendazole against helmi of 2,5 to 3,8 mg/kg administered orally, resulted in a 98,8 to 100% reduction of adult parasites of the genera Haemonchus, Ostertagia, Trichostrongylus, Nematodirus, Gaigeria, Oesophagostomum, Chabertia, Marshallagia and Cooperia. Against the immature stages of these genera, except for Marshallagia and Cooperia, which were not tested, a dose level of 2,5 to 3,8 mg/kg was 83,9-100% effective. Albendazole at 2,5 mg/kg was 99,0% effective against adult stages of Dictyocaulus; its activity at a dose of 3,8 mg/kg against the immature stages of D. filaria was 89,3%. In sheep naturally infested with Moniezia, 100% elimination was obtained at a dose level of 2,5 mg/kg. Dose levels of 3,8 mg/kg and higher were more than 76% effective against adult Fasciola hepatica, while a dose of 4,8 mg/kg was 63% effective against adult Fasciola gigantica.


The safety of fenthion 29% m/v when applied topically to pregnant cows. A pilot trial was conducted with fenthion 20% m/v to determine possible abortifacient or other toxic effects when applied to 4 1/2 month pregnant beef cows. No abortions or other clinical symptoms which could be attributed to the fenthion were observed after two topical applications, at a 3-week interval, of up to 5 times the therapeutic dose.


Bovine cerebral theileriosis (turning sickness) with spinal cord involvement. A case of bovine cerebral theileriosis is described in which the principle lesions occurred in the spinal cord and its meninges. These were clogging of vessels with lymphocytes, many of which were parasitised by Theileria sp. schizonts (probably T. mutans), thrombosis and infarction of nervous tissue, and lymphocytic meningomyelitis. Rare cerebral meningeal vessels showed thrombosis. Clinically the animal showed posterior paresis.


A previously unrecorded feeding site on cattle for the immature stages of the spinose ear tick, Otobius megnini (Dugès, 1844). During the rainy season in the central valley of Cochahbamba, Bolivia, the larvae and nymphae of this tick were found feeding under the tails of dairy cattle as well as in their ears. The conditions that apparently favour the temporary infestation of this site on some cows are discussed briefly.


[Symptoms of rabies in pets and domestic animals in South Africa and South West Africa (author's transl)]. The most obvious symptoms of rabies in farm animals and pets in South Africa and South-West Africa are discussed in the light of information obtained during routine examination of specimens for the 10-year-period 1967--1976. More than 55% of the cases encountered were cattle in which the most obvious symptoms were salivation (92%), bellowing (69%), aggressiveness (47%), paresis or paralysis (30%) and straining (12%). Unlike cattle, the most obvious symptom in goats was aggressiveness (83%). Salivation was observed in ony 29% of goats but, like bellowing in cattle, bleating was very obvious in 72% of cases. Sheep were usually quiet, but 67% were aggressive. Salivation was observed in 30%, while 27% showed an abnormal sexual desire. The second highest incidence of rabies was recorded in dogs (20%). Aggressiveness was the most obvious symptom (71%) followed by salivation (48%), paresis and paralysis (28%) and barking (11%). With the exception of salivation and paresis, which were rarely encountered, aggressiveness was the only symptom observed in cats. Several cats were encountered with rabies-like symptoms due to organic phosphate poisoning. The most obvious symptoms in horses and donkeys were aggressiveness (77%), paresis or paralysis 33%), the chewing of foreign matter (33%) and salivation 22%). It is obvious that other conditions can easily be confused with rabies. Therefore every possible cause for rabies-like behaviour must be considered and eliminated to avoid unnecessary destruction of animals.


The restraint of the Cape Hunting dog Lycaon pictus with phencyclidine hydrochloride and ketamine hydrochloride. Phencyclidine HCl and ketamine HCl were used as immobilizing agents on six captive Cape Hunting dogs. Both drugs were suitable and three dogs immobilized with ketamine HCl at a dosage rate of 7 mg/kg had smoother and shorter recovery periods than the three animals immobilized with phencyclidine HCl.


Some aspects of feeding of brood gilts and sows. The amounts of feed required during each of the reproductive phases are graphically illustrated and supported by specific recommendations where possible with discussion of the underlying rationale and of the often conflicting considerations. For flushing, an increase of 50 to 100% of energy requirements above maintenance level is recommended, supplied, for example, by one to two kg maize extra per day during the week before expected oestrus, in order to increase the ovulation rate. During pregnancy a constant feeding level is proposed 2.2 to 2.5 kg of feed with 8.8 MJ of nett energy/kg and 12% digestible crude protein being necessary. Two days before farrowing the feeding level must be lowered and steps taken to keep the gut contents to a minimum. During lactation the feed has to contain 8.8 MJ nett energy/kg and 14% digestible crude protein and the intake reduced by 10 to 20% in the case of early weaning. At weaning a fasting regime is suggested to effect physiological stress. The relation between feeding level during pregnancy and the mass gain of the sow asnd number of piglets born, as well as on the birth mass of the piglets, and the relation between N intake and N retention and litter mass oat birth are shown graphically.


Nutritional myopathy in a dog.

Nutritional myopathy in a dog. A case of cardiac myopathy resembling Selenium-Vitamin E Deficiency myopathy is described in a puppy. The left ventricular myocardium was extensively involved. The macroscopic and microscopic appearances are described. The literature on the subject is briefly reviewed.


Canine encephalitozoonosis in South Africa. Clinical, clinicopathological macroscopical and histopathological findings, as well as electron microscopic and cultural confirmation, in twelve natural cases of canine encephalitozoonosis are described, eleven of these under one year of age. Nervous symptoms, including blindness, retarded growth rate and nephritis are prominent clinical signs. The macroscopic findings and histopathology proved of great help in the diagnosis of the disease even in chronic cases. The organism was cultured and some distinguishing electron microscopical features between Encephalitozoon and Nosema are discussed. A transmission experiment confirmed the diagnosis. The results are compared with the reported cases in dogs and Blue Foxes (Alopex lagopus).


[The effect of sodium hydroxide-treated roughages in horses: I. Treated lucerne hay as a constituent of a complete ration for foals (author's transl)]. The possibility of including sodium hydroxide-treated lucerne hay as a constituent in rations for horses was investigated by measuring its effect on the performance and certain bloodcomponents of growing foals. As no adverse effects were found it is concluded that further investigation is necessary to see whether the inclusion of low grade-treated roughages in the ration of horses would be of economic significance.


A specific form of abomasal phytobezoar in goats and sheep. A specific form of phytobezoar in goats and sheep is described with regard to epizootology, symptomatology, gross pathology, and gross morphology of the bezoars. The probable mode of formation and control measures are also discussed.


The use of a short and a long acting oxytetracycline for the treatment of Anaplasma marginale in splenectomized calves. Twenty splenectomized Afrikander/Simmentaler cross animals were used. Eight of these were naturally infected with Anaplasma marginale while 12 were infected artificially. When the packed cell volume was reduced to between 24% and 20% during the post splenectomy relapses or primary infections, six animals were treated with a single injection of 20 mg/kg of long acting oxytetracycline (LA) and seven animals were treated on two successive days with 10 mg/kg of short acting oxytetracycline (SA). The remaining seven animals served as untreated controls. Both drugs were effective in controlling A. marginale reactions. No deaths occurred in the group of animals treated with oxytetracycline LA and they showed a longer relapse interval and higher blood levels of oxytetracycline compared to those treated with oxytetracycline SA. A single death occurred in the latter group. Four deaths occurred in the control group which also had the shortest relapse interval.


The effect of the dye-marking of mastitis remedies on the incidence of antibiotic residues in Pretoria's market milk supplies. A 1973 survey on the incidence of inhibitory substances (mostly antiobiotic residues) in market milk supplied in Pretoria, on 3 195 herd milk samples, 65 tanker milk samples and 252 samples of pasteurised milk using the disc assay procedure with Bacillus stearothermophilus C 953 as test organism, revealed inhibitory substances equivalent to 0,005 IU penicillin/ml in 7.8% of the herd samples, 29,2% of the tanker samples and in 38.5% of the samples of pasteurised milk. In 38.9% of the positive herd milk samples and 73% of the samples of pasteurised milk, penicillin was indentified with the aid of the penicillinase test. Some of the pasteurised milk contained inhibitory substances equivalent to more than 1.0 IU penicillin/ml; in some of the herd milk samples this figure exceeded 5,0 IU penicillin/ml. A repeat survey was undertaken in 1977/78 to evaluate the effect of compulsory dye-marking of non-prescription mastitis remedies on the situation. In a total of 1 081 herd milk samples, 60 tanker milk samples and 112 samples of pasteurised milk, antibiotic residues were found in 2,13% of the herd milk, 11,7% of the tanker milk and 2,1% of the pasteurised milk samples, with a much lower average concentration of antibiotic residues. The compulsory dye-marking of mastitis remedies had a beneficial effect on the occurrence of antibiotic residues in milk but did not ensure their complete absence, presumably because dye-marking was not made compulsory in scheduled preparations.


Rift Valley fever vaccine--antibody and immune response in cattle to a live and an inactivated vaccine. In a study of the response in cattle to a live and an inactivated Rift Valley fever (RVF) vaccine prepared from cell cultures infected with RVF virus, the effects of varying doses and combinations of these vaccines were compared. The antibody response to a primary injection of either vaccines was poor when measured by the serum virus neutralization test (SVN) and the haemagglutination-inhibition test (HI) but a booster dose of inactivated vaccine evoked a good anamnestic response in cattle previously injected with either of these vaccines. Cattle vaccinated with the live vaccine but negative to the SVN or the HI for RVF were immune when challenged with a virulent RVF virus isolated from a cow during 1974.


An outbreak of white muscle disease in lambs born of ewes on a zero grazing system in Natal. White muscle disease appeared in lambs born of ewes in the zero grazing group during the course of a comparative fertility trial on ewes on various systems of husbandry. Analysis of the feed showed barely adequate selenium in the maize silage and a deficiency in the soil on which the high lysine maize was grown. Treatment of the lambs with a selenium/vitamin E injection rapidly controlled the condition. This deficiency may be more widespread than is presently realised.


Canine encephalitozoonosis in kennels and the isolation of Encephalitozoon in tissue culture. The protozoan Encephalitozoon was isolated in primary kidney cultures from dogs originating from three separate outbreaks of encephalitozoonosis in kennels. The disease was characterized by a fading syndrome in young puppies with nervous signs developing in some cases. It was not possible to reproduce the clinical disease with cultured organisms in either normal dogs or dogs immunosuppressed with methylprednisolone. The organisms were, however, reisolated in primary culture from two immunosuppressed dogs but not from other experimentally infected dogs. The freezing of Encephalitozoon organisms in liquid nitrogen is described.


Cartilage healing and regeneration.

Cartilage healing and regeneration. A study was undertaken to investigate the healing and regeneration of articular cartilage following trauma. Surgically created superficial and depp lesions involving the articular surface of the femoral condyles were evaluated in 28 dogs at intervals of two four, eight and sixteen weeks. The general conclusion reached was that cartilage resonded to trauma either with fibrous tissue repair (undergoing metaplasia to fibro--cartilage) when the lesion was deep, or by limited cellular replacement before the superficial layers became reorganised into zones resembling the normal, if the lesions were superficial. This process tended to tail off before the defect was filled i.e. the regenerative process appeared to cease before the lesion was anatomically restored to normal.


Hand-rearing of Cape hunting dog Lycaon pictus pups. Problems encountered in the hand-rearing of Cape hunting dogs are discussed. It is felt that these could be minimised by avoiding stress, by rearing pups as close to natural circumstances as in possible, by applying sound husbandry techniques and by keeping the pups together.


Foreleg lameness in rapidly growing dogs. Foreleg lameness caused by the interaction of diet and rapid growth rate is all too frequently encountered in the large and giant breeds of dogs. In this paper, the influence of rapid growth rate and growth hormone on bone formation is briefly considered. The importance causes of this problem are discussed. These are hypertrophic osteodystrophy, osteodystrophy II, retained enchondral cartilage cores, panosteitis an nutritional secondary hyperparathyroidism. Rickets and hypertrophic pulmonary osteoarthropathy are also considered. Emphasis is placed on the aetiology, radiographic diagnosis and rational treatment. A case report of a 6-month-old Great Dane with osteodystrophy II and retained enchondral cartilage cores in the ulnar metaphyses is presented as an example of such a problem.


Canine thoracolumbar disc disease.

Canine thoracolumbar disc disease. The incidence, pathology and accurate localisation of canine intervertebral disc lesions are reviewed and the surgical technique for wide dorsal laminectomy is described.


Canine cervical intervertebral disc disease. The incidence, diagnosis and surgical treatment of canine cervical disc lesions are described.


Toxoplasmosis in a dog.

Toxoplasmosis in a dog. The clinical, clinical pathological and pathological findings of a dog showing progressive paralysis due to toxoplasmosis are described. Necropsy revealed polymyositis and a meningoencephalitis as well as a meningomyeloradiculitis. The differential diagnoses of the different forms of toxoplasmosis are briefly discussed.


[Feline hepatozoonosis (author's transl)]. The pressure of the gametes of the protozoon parasite Hepatazoon in the blood of a domestic cat is recorded for the first time in South Africa. Clinical symptoms which may have been associated with the infection are described. The animal recovered after treatment with primaquine and oxytetracycline.


Determination of penicillin residues in milk - a comparison of two methods. Two tests for penicillin residues in milk using the test organisms Sarcina lutea and Bacillus stearothermophilus var. calidolactis respectively are presented. The test methods are described, the results compared and the advantages of the latter test demonstrated.


Corrosion of stainless steel surgical implants. In the light of examination of a series of failed stainless steel implants, the paper suggests that much material currently used for orthopaedic prostheses is not of a sufficiently high metallurgical quality for its purpose.


Time correction and two channel recording in 24 hour electrocardiographic analysis. An improved technique for automatic monitoring and analysis of ECG recording is described. The system is based on standard commercial equipment but provides improved quantitative measurement of cardiac arrhythmias. This is done by using a simultaneous recording of a 100 Hz clock, which is used to correct for tape speed variations. Also increased immunity to artefacts is achieved by combining two ECG leads, coupled with signal analysis techniques. The problems arising from certain types of artefact are also discussed.


Position of bioengineering education in Hungary. Medical electronic equipment has been produced in Hungary since the early forties. Industrial production of bioengineering started only in 1957. At the same time the bioengineering section of the Scientific Society of Measurement and Automation was founded. This Section was instrumental in recognizing the necessity for and establishing a structured education programme in bioengineering which started in the Postgraduate Institute for Engineers within Budapest Technical University. Later this was incorporated in the programme of the Technical University as an optional subject. Today there is also a specialised engineering course at the Technical University. There are significant developments in the bioengineering education of physicians and medical students. This paper deals with the possibility of classification bioengineering devices which has proved useful in education in Hungary.


[Electromyographical studies on the effects of dorsal and truncal vagotomy upon the motility of abomasum in goats (author's transl)]. The vagus nerve was examined electromyographically for effect on the abomasal movement in adult female goats subjected to dorsal or truncal vagotomy. The results obtained are summarized as follows. 1. After dorsal vagotomy, the discharge interval prolonged slightly and the propagation velocity decreased. 2. After truncal vagotomy, the propagation velocity did not show a remarkable change except that the discharge interval showed a tendency to prolong slightly. 3. Neither dysrhythmia nor antiperistaltic discharge was seen after dorsal or truncal vagotomy. 4. The movement of the reticulum showed a tendency to be affected with temperature after dorsal vagotomy. It was not recorded after truncal vagotomy. The goats vagotomized dorsally showed an increase in body weight and decrease in volume of feces accompanied with repeated bloat. The goats vagotomized truncally died of acute frothy bloat 2-10 days after operation. Therefore, it was suggested that truncal vagotomy might have exerted a greater effection all the stomach of the ruminant than dorsal vagotomy, which reduced the movement of rumen more remarkably than the movement of the abomasum.


[Electromyographic study of the canine stomach after transection and mucosal bridge anastomosis (author's transl)]. In order to clarify the propagation mechanism of canine gastric electrical activity, the stomach was transected and reanastomosed at the middle antrum in 3 dogs and at the distal corpus in 3 dogs. Two bipolar electrodes were implanted in the pre- and postanastomosis stomach. Electromyographic recordings were performed intermittently for 8 to 13 weeks in fasting and after feeding. In one of the 6 dogs, 11 weeks after the initial surgery, one half of the anterior muscle wall of the greater curvature side was reapproximated. In fasting, the BER interval in the preanastomosis remained unchanged, but that in the postanastomosis became prolonged. After feeding, the BER interval in the postanastomosis was shortened and showed an advancement to close to that in the preanastomosis. 3 weeks after reapproximation of partial muscle wall, the BER interval in the postanastomosis recovered to the same BER interval as in the preanastomosis in fasting and after feeding stages. Dysrhythmia in the postanastomosis was of temporal occurrance. These results suggest that an inherent automatism in the gastric wall plays a role in the recovery of the BER interval and close muscle approximation is essential for propagation of gastric electrical activities.


[Electromyographic study on the propagation mechanism of canine gastric electrical activity (author's transl)]. In order to clarify the propagation mechanism of the canine gastric basic electrical rhythm (BER), a complete transection-reanastomosis was done in the lower corpus, corpus-antrum junction or middle pyloric antrum in each group of 3 dogs which had been equipped with 4 bipolar electrodes. At the time of the transection-reanastomosis, 4 pacing electrodes were also implanted. The BER frequency in the preanastomosis, 4 pacing electrodes were also implanted. The BER frequency in the preanastomosis remained unchanged regardless of the site of transection-reanastomosis, while that in the postanastomosis was markedly reduced, but gradually recovered to show the synchronization with the BER in the preanastomosis. Pacing of the gastric BER in the early stage (about 10 days post op.) when the synchronization was noted, was not established through anastomosis. However, pacing in the late stage (about 30 days post op.) was established through an astomosis. Dysrhythmia in the postanastomosis were observed to occur in high incidence in the early postoperative period, but subsequently declined to the same incidence as in the controls. Therefore, the synchronized phenomenon is due partly to the recovery of the inherent automatism of the gastric wall and due to subsequent propagation of the BER through anastomosis. Dysrhythmia in the postanastomosis were of temporal occurrence.


[The motility of the bile ducts in pigeons and the effects of some autonomic drugs on it (author's transl)]. The motility of the bile ducts of the pigeon and the effects of autonomic drugs on it were studied in vivo and in vitro. Peristalses which originated rhythmically at the hepatic end of the duct propagated to the duodenal end and excreted the bile into it. Antiperistalses did not occur in vivo. The intervals of peristalses of the duct in vivo changed variably while those of the spontaneous contractions in the isolated duct were fairly constant. No synchronization between the electrical activities recorded at the duodenal end of the duct and the duodenum close to the duct was observed. Cholinergic drugs increased motilities of the duct and duodenum. Adrenaline, noradrenaline and phenylephrine induced the excitation of the duct and isoprenaline slight inhibition. All of these sympathomimetic drugs inhibited duodenal motility. The excitatory effect was abolished by alpha-adrenergic blocking agent, and the inhibitory one was abolished by alpha- and/or beta- adrenergic blocking agents. These results suggest that the bile duct is functionally independent of the duodenum and responsibility of the adrenergic drugs are different between two organs.


Juvenile and late onset forms of depressive disorder: genetic and biological characterization of bipolar and unipolar illness-a review. The age of onset of depressive illness may have an association with the genetic character and clinical course of the disorder. There are several genetic models of depressive disorder that are based on differences in age of onset. According to a multifactorial model, for example, a late onset would indicate a small genetic and greater environmental component. A correlation has been found between positive family histroy of affective illness and early age of the first episode. The presence or absence of a family history of affective illness has also been found to be distinguished by pharmacology, physiology, symptomatology, and severity. It is therefore recommended, for purposes of diagnosis and treatment, that a family history be gathered for patients with depressive illness.


Cytologic evaluation of hormonal dynamic in the postmenopause. There is increasing evidence that the postmenopausal ovary retains some endocrine function and thus can contribute a certain extent to the persistence of the vaginal epithelium proliferation a long time after the cessation of menstruations. Vaginal cytology plays an important role in the assessment of the vaginal epithelium response to hormonal stimuli, though less accurate than the blood and the urine estimations. It was established that there was a good correlation between the vaginal cytology and the biochemical estimations [2]. The fact that vaginal cytology cannot distinguish the proliferative patterns induced by estrogens, progesterone and androgens is true. With this in mind we did a cytological study in postmenopausal women, using our classification for the cytological typing based on the depth of the epithelial atrophy. The findings are discussed with special reference to the ethnic origin, reproductive life and concurrent illnesses.


Haemodynamic and hormonal effects of short-term oestradiol treatment in postmenopausal women. Haemodynamic changes during a 3-wk treatment with oestradiol valerianate (2 mg/day orally) were studied in 12 postmenopausal women by isotope 113Inm radiocardiography. Systolic blood pressure measured in the supine position decreased during oestradiol treatment by 3% (P less than 0.05) and the diastolic blood pressure decreased by 4% (P less than 0.01). The heart rate decreased by 15% (P less than 0.001). Blood volume increased during oestrogen treatment by 5% (P less than 0.05) whereas cardiac output decreased by 9% (P less than 0.05). Stroke volume increased by 13% (P less than 0.001) due to concomitant decrease in heart rate. Changes in plasma oestrone and oestradiol concentrations during oestradiol valerianate substitution showed a positive correlation with the changes of blood volume.


Hysterography in evaluating the uterine cavity in patients with endometrial carcinoma. In 49 patients with endometrial carcinoma hysterographic study was performed. This finding was correlated with fractional curettage, hysteroscopy and surgery. The best correlation was noted between hysterography and hysteroscopy. The flow into the tubes or abdominal cavity using low pressure was found in 20% of the cases. In our opinion hysterography is a useful aid when examining the uterine cavity and cervical canal, and, thus, important when planning treatment and determining clinical stage.


Factors affecting adhesion of bacterial to a tooth in vitro. The initial adhesion of oral bacteria to a tooth in vitro was examined. The organisms were grown in broth with and without sucrose, and suspensions made either in broth or a modified Ringer's solution. The tooth used was either dry or coated with natural or synthetic saliva. Adhesion was determined by counting organisms removed from the tooth surface by simple washing or by sonication. It was found that the firmest bonding occurred when a dry tooth was immersed in a suspension of bacteria in Ringer's solution; the prior growth of the organisms in the presence of sucrose did not affect adhesion. It was concluded that instantaneous irreversible adhesion of bacteria to a tooth occurs without the need for active metabolism, and that this process is inhibited by the presence of competing organic substances which probably produce a surface-conditioning film.


Inhibitory activity of Streptococcus mitis against oral bacteria. The antagonistic properties of three strains of Streptococcus mitis were investigated. They were found to inhibit a wide range of oral bacteria; Gram-positive and Gram-negative, facultative and anaerobic species being susceptible. The S. mitis strains were shown to be producing hydrogen peroxide, this being partially responsible for the aerobic inhibitory activity. A second inhibitory factor(s) was also produced, aerobically and anaerobically, although this could not be isolated. A limited characterization of this factor was undertaken using plate cultures.


Effect of storage on the integrity of purified feline calicivirus particles. The effect of storage on the integrity and infectivity of purified feline calicivirus (FCV) particles at varying temperatures (-70 degrees C, -20 degrees C and 4 degrees C) was examined. The results showed that over a period of 8 weeks the purified virus was best preserved at 4 degrees C.


An in vitro study of the exposure of mixed populations of normal oropharyngeal bacteria to cigarette smoke. Mixed populations of freshly isolated oropharyngeal bacteria growing in dextrose broth at 37 degrees C were subjected to smoke from four cigarettes over a 3 h period. Each cigarette, a commercially available brand, contained 23.0 mg of tar and 1.4 mg of nicotine. At hourly intervals eight puffs of smoke from a cigarette were passed over a 1.0 ml suspension of bacteria dispersed in a thin layer in a sterile tissue culture flask. Normal filtered air was in contact with the suspension between smoke treatments. Exposure to cigarette smoke resulted in a marked decrease in numbers of viable bacteria. Non-filter cigarette smoke had a greater detrimental effect than smoke from filter-tipped cigarettes. The predominant bacteria, non-haemolytic streptococci, and less numerous bacteria such as staphylocci, were equally sensitive to the toxic action of cigarette smoke.


On the organization and classification of the protozoon, Actinophrys sol Ehrenberg, 1830. The organization of the heliozoon Actinophrys sol is described using light-microscopy, transmission and scanning electron-microscopy, freeze fracturing and X-ray microanalysis. The features of the trophic organism and its organelles are described in detail. The processes of encystment, autogamy and excystment are outlined. Encystment involves the production of siliceous scales which are destined to become one layer of a resting cyst with a multilayered cyst wall. Autogamy occurs before the resting cyst is formed. Cytoplasmic peculiarities of the trophic organism are almost entirely absent from the resting cyst but reappear upon excystment. The structural characteristics are used to assess the affinities of Actinophrys with other actinophryids, heliozoons, actinopods and sarcodina. It is concluded that the justification of the conventional classification of Heliozoa is questionable.


Nucleotide sequence of a region of human mitochondrial DNA containing the precisely identified origin of replication. A fragment of HeLa cell mitochondrial DNA containing the origin of replicaton has been sequenced. The precise position of the origin in this sequence has been identified by determining the nucleotide order in the 5'-end proximal portion of the heavy strand initiation fragment (7S DNA), and by aligning the two sequences.


A role for brown adipose tissue in diet-induced thermogenesis. Measurement of energy balance during voluntary overeating in rats unequivocally establishes the quantitative importance of diet-induced thermogenesis in energy balance. Like cold-induced thermogenesis, this form of heat production involves changes in the activity of the sympathetic nervous system and brown adipose tissue which suggest that this tissue may determine metabolic efficiency and resistance to obesity.


Rabbit beta-globin mRNA production in mouse L cells transformed with cloned rabbit beta-globin chromosomal DNA. Mouse thymidine kinase-negative L cells were transformed with a cloned rabbit chromosomal beta-globin gene linked to the clone thymidine kinase gene of herpes simplex virus type 1. Most thymidine kinase-positive cell lines contained one or more copies of rabbit beta-globin DNA and produced up to 2,000 copies of rabbit beta-globin RNA per cell indistinguishable from its authentic counterpart. No mouse beta-globin mRNA was detected.


Protein deprivation causes reversible impariment of mucosal immune response to cholera toxoid/toxin in rat gut. Scretory antibodies may be the major defence against mucosal infections, especially those due to viruses and non-invasive pathogens such as Vibrio cholerae and toxinogenic Escherichia coli. The high incidence of mucosal infections in malnourished protein-deficient children may result from defective antibody production, but evidence for this is conflicting. We report here that protein deficiency markedly impairs the mucosal immune reponse to cholera toxiod/toxin (CT), a protein antigen, in rats and that this impairment is rapidly reversed by refeeding.


GABA may be a neurotransmitter in the vertebrate peripheral nervous system. gamma-Aminobutyric acid (GABA) is an inhibitory neurotransmitter in the peripheral nervous system of certain invertebrates and is thought to be a major transmitter in the vertebrate central nervous system. In this report we present evidence that GABA may also be a neurotransmitter in the vertebrate peripheral autonomic nervous system. We have used light and electron microscopic autoradiography to analyse high-affinity uptake of 3H-GABA into the myenteric plexus of the guinea pig taenia coli, both in situ and in a tissue culture preparation. In the isolated myenteric plexus, we have measured the specific activity of glutamic acid decarboxylase (GAD; EC 4.1.1.15), the enzyme responsible for conversion of glutamic acid to GABA in GABAergic neurones, and assessed the ability of this tissue to accumulate 3H-GABA newly synthesised from 3H-glutamic acid. Furthermore, we have measured the levels of endogenous GABA in strips of taenia coli containing the myenteric plexus.


Energy dependence and reversibility of membrane alterations induced by polyene macrolide antibiotics in Chlorella vulgaris. The requirement of metabolic energy for the interaction of polyene macrolide antibiotics with eukaryotic organisms remains a controversial subject (for review see ref. 1) It has been claimed that the lethal binding of these antibiotics to the sterol target component of the hydrophobic core of the membrane, in accordance with the model of de Kruijff and Demel, is an energy-dependent process. When energy production is reduced by removal of all metabolisable substrates or by adding metabolic inhibitors, polyene binding and antifungal effects are also reduced. Metabolic energy may be required to maintain binding site accessibility or to move antibiotic molecules to the active site. The interaction is also restricted at low temperatures, possibly because of the reduced thermal mobilities of the groups concerned with antibiotic uptake. However, it should be emphasised that the interaction of polyene macrolides with artificial lipid membranes is a purely physicochemical process, although the type of permeability pathways induced are similar to those observed in natural membranes. Using Chlorella vulgaris as a model organism, we demonstrate here that the interaction of polyene macrolides with sensitive cells and the induction of lethal membrane permeability changes are energy-dependent processes or purely physicochemical phenomena, depending on the structure of the antibiotic used.


An incipient 3(10) helix in Piv-Pro-Pro-Ala-NHMe as a model for peptide folding. The molecular mechanism of helix nucleation in peptides and proteins is not yet understood and the question of whether sharp turns in the polypeptide backbone serve as nuclei for protein folding has evoked controversy. A recent study of the conformation of a tetrapeptide containing the stereochemically constrained residue alpha-aminoisobutyric acid, both in solution and the solid state, yielded a structure consisting of two consecutive beta-turns, leading to an incipient 3(10) helical conformation. :This led us to speculate that specific tri- and tetrapeptide sequences may indeed provide a helical twist to the amino-terminal segment of helical regions in proteins and provide a nucleation site for further propagation. The transformation from a 3(10) helical structure to an alpha-helix should be facile and requires only small changes in the phi and psi conformational angles and a rearrangement of the hydrogen bonding pattern. If such a mechanism is involved then it should be possible to isolate an incipient 3(10) helical conformation in a tripeptide amide or tetrapeptide sequence, based purely on the driving force derived from short-range interactions. We have synthesised and studied the model peptide pivaloyl-Pro-Pro-Ala-NHMe (compound I) and provide here spectroscopic evidence for a 3(10) helical conformation in compound I.


Contact inhibition and malignancy.

Contact inhibition and malignancy. The role of contact inhibition in influencing the behaviour of malignant cells is discussed in a review. Although tissue culture cannot simulate the immense complexity of the conditions in vivo, some of the distinctive features of malignant invasion can be conveniently observed with this technique. The evidence derived from this technique indicates that defective contact inhibition of movement of malignant cells does contribute to their invasiveness.


Two-step binding of eukaryotic ribosomes to brome mosaic virus RNA3. Although brome mosaic virus RNA3 has only one translatable cistron, it can bind two 80S ribosomes at initiation. One ribosome binds at the first AUG codon (base 92-94). The other binds nearer the 5' end at an entry or holding site. Disome formation is thus unrelated to a silent cistron approximately 1,000 bases downstream.


Rapid deposition of subcutaneous areolar tissue in response to sexual stimulation in mice. Many of the reproductive processes of house mice are regulated exteroceptively by social cues. Puberty in a female mouse, for example, is a labile event that can be accelerated markedly if the young female is housed with an adult male. The relevant male stimuli in this case are a combination of pheromonal and tactile cues. The female's responses to these cues include an immediate, sequential release of gonadotropic and ovarian hormones, which in turn evoke a series of predictable changes in most of the female's reproductive tissues and culminate in the pubertal ovulation. I report here an unexpected consequence of exposing a young female mouse to a male, namely an intense response of a non-reproductive tissue. Specifically, young female mice experience a rapid thickening of their subcutaneous areolar tissue when they are exposed to males. The proximal cause of this response seems to be largely, but not exclusively, an enhanced secretion of ovarian oestrogen.


Zoological origin of gonadotropin subunits and association kinetics. Mammalian luteinizing hormone (LH) is an association of two dissimilar subunits, alpha and beta. In vitro studies, mainly using difference spectrophotometry, had shown that this phenomenon was slow, especially at low temperatures. If the situation was the same in poikiloterms, it would probably make gonadotropin (GTH) synthesis difficult for these animals in a cold environment. We have found that the formation of a teleost gonadotropin is in fact strikingly more rapid and less thermodependent than formation of mammalian LH. Also, studies with a fish-mammal hybrid molecule have allowed us to estimate the respective influence of the alpha and beta subunits in determining these differences.


Design, synthesis and characterisation of a 34-residue polypeptide that interacts with nucleic acids. Based on secondary structure prediction rules and model building a neutral artificial 34-residue polypeptide with potential nucleic acid-binding activity was synthesised. This peptide and its covalent dimer showed strong interaction with cytidine phosphates and single-stranded DNA. The dimer had considerable ribonuclease activity with high preference for cleavage at the 3'-end of C.


Inhibition of platelet aggregation by native and desialised alpha-1 acid glycoprotein. The alpha-1 acid glycoprotein (orosomucoid; AAG) is a normal constituent of human plasma (650+/-215 microgram ml(-1)) which increases in concentration as much as fivefold in associations with acute inflammation and cancer, and thus is recognized as an acute phase protein. AAG consists of a single polypeptide chain, has a molecular weight of 44,100, and contains approximately 45% carbohydrate including 12% sialic acid; it is the most negatively charged of the plasma proteins. Certain of the biological properties of AAG are related to its sialic acid content; thus, clearance and immunogenicity of AAG are markedly increased on desialisation. The biological functions of AAG are largely unknown. AAG has the ability to inhibit certain lymphocyte re-activities including blastogenesis in response to concanavalin A, phytohaemagglutinin and allogeneic cells, and these inhibitory effects are enhanced in association with desialisation. In view of these observations, a report that unphysiologically large (5--15 mg ml(-1)) amounts of AAG inhibit the platelet aggregation induced by ADP and adrenaline, and evidence that a sialic acid-deficient species of AAG appears elevated in several chronic disease states, we compared the effects of AAG and its desialised counterpart (AAG-D) on platelet aggregation. We report that desialisation of AAG is associated with increased expression of activity inhibitory to the platelet aggregation otherwise observed on stimulation with ADP, collagen or thrombin.


Ca2+-induced fusion of phospholipid vesicles monitored by mixing of aqueous contents. Ca2+ has a central role in various cellular phenomena involving membrane fusion. However, little is known about the mechanisms involved. Model membrane systems such as phospholipid vesicles have been used extensively to study the mechanism of membrane fusion at the molecular level. For example, phosphatidylserine (PS) vesicles have been shown to undergo massive aggregation and structural rearrangements on additon of Ca2+, with eventual formation of large cochleate structures. Although these structures do not retain appreciable internal volume, their formation has been proposed to result from fusion of the initial vesicles. The significance of the PS--Ca2+ system as a model for biological membrane fusion has been questioned recently by Ginsberg. Based on the observation that divalent cations induce the release of contents from PS vesicles but fail to bring about the uptake of a marker from the medium, he proposes that the vesicles are ruptured completely during interaction with divalent cations and reassemble subsequently to form large non-vesicular structures. The present study demonstrates that the question raised by Ginsberg is not particularly relevant to the phenomenon concerned, and that his experimental observations do not allow the exclusive conclusion that Ca2+ induces lysis of PS vesicles rather than fusion.


Biological degradation of TCDD in rats.

Biological degradation of TCDD in rats. Apart from its high toxicity, the chemical stability and persistence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the environment bring about additional hazards. However, until now there has been no evidence for degradation of this dioxin in biological systems, and it is considered unusual that a compound which is insusceptible to biological attack should be so extremely toxic. In in vitro studies with microsomal preparation from mouse, rat and rabbit liver, as well as in vivo, no metabolite of TCDD has been detected by several workers. Recent data, showing a lower toxicity of TCDD in rats after stimulation of the hepatic mixed-function oxidase, suggested possible metabolic transformation of this compound. In the present study, we used tritiated TCDD to search for metabolites in the bile of rats and found marked changes in lipophilicity and mobility in TLC of the excreted radioactivity. Treatment with diazomethane yielded at least two new compounds. These observations hinted at the formation of phenolic hydroxyl groups in the dioxin molecule.


Organization and sequence studies of the 17-piece chicken conalbumin gene. The conalbumin gene has been cloned and shown to consist of at least 17 exons approximately 60-200 base pairs long. The DNA sequence upstream from the region coding for the 5' end of the mRNA shows similarities with sequences present in homologous positions in other genes. High and low frequency repetitive sequences are found both upstream from the conalbumin gene and within one intron.


Equilibrium: the intracellular distribution of steroid receptors. Data are presented which suggest that there are unbound receptors for oestrogen in nuclei of the smooth muscle cells of the myometrium. A new model for the distribution of unbound receptors is proposed in which unbound receptor is in equilibrium, partitioned between nucleus and cytoplasm according to the free water content of these intracellular compartments.


Localisation of phencyclidine-induced changes in brain energy metabolism. The abuse of phencyclidine [1(1-phencylohexyl)piperidine, PCP], commonly referred to as angel dust or hog, is rapidly reaching epidemic proportions. PCP users often appear violent and increases in PCP-implicated homicides and suicides have been reported. In animal studies PCP has been demonstrated in brain up to 48 h after administration, long after blood levels become undetectable. However, there is little further information on the distribution of PCP within the central nervous system with regard to the possible sites of action. Recently, Sokoloff and associates described a new technique which can be used to visualise possible sites of drug action. The technique is based on the premise that neuronal activity is closely related to energy metabolism. Therefore, by directly monitoring 2-deoxy-D-glucose consumption before and after a pharmacological stimulus, we can obtain autoradiographic evidence of changes in neuronal activity in discrete areas brain as a response to that stimulus. Using this procedure, we now report that PCP causes dramatic changes in glucose metabolism in very specific regions of the rat brain.


Relationship between crystallin mRNA expression in retina cells and their capacity to re-differentiate into lens cells. Differentiating vertebrate embryo tissues pass through a stage when they have the potential for several pathways of differentiation, some of them revealed only by experimental manoeuvres. As differentiation proceeds, the potential for alternative pathways becomes progressively restricted and is eventually lost. We have investigated the molecular basis for this phenomenon, using the chick embryo retina, which has a potential for differentiation into lens cells. This potential requires special conditions for its manifestation; it declines during development and is finally lost before hatching. Lens protein (crystallin) mRNA is expressed in early embryo retina: its levels decline in parallel with the decline in lens-forming potential. There is also evidence of an ontogenic change in post-transcriptional regulation. Such a relationship between heterologous mRNA and heterologous differentiation potential may be of general application.


Reproductive dysfunction in male rats following neonatal administration of monosodium L-glutamate. Monosodium glutamate (MSG) was administered to neonatal rats according to an increasing dose schedule from days 2-11 after birth. Adult MSG-treated male rats showed reproductive deficits along with stunted body lengths and reduced testes weights. These results demonstrate that MSG is capable of producing reproductive deficits in the rat similar to those seen in the mouse. These results are discussed in light of the methodological differences between those studies reporting positive or negative findings on reproductive function in MSG-treated mice and rats.


Hippocampal afterdischarges and their post-ictal sequelae in rats: effects of carbon monoxide hypoxia. A series of experiments was performed to examine the utility of using the properties of artifically induced seizures as indices of the toxic effect of CO upon the CNS. The two behavioral seizure models tested, 6 Hz ECS and pentylenetetrazol, were unable to differentiate between exposed and unexposed animals, even at severe concentrations of CO (55% HbCO). On the other hand, the hippocampal afterdischarge (AD) proved to be at least as sensitive as the visual evoked potential method. There was a CO concentration-dependent shift in the AD type. CO increased the probability of occurrence of post-ictal depressions (PIDs) without rebound ADs, an event never seen in control animals. CO also decreased the spike frequency within ADs in a dose-dependent manner.


Effects of maternal absorption of phenobarbital upon rat offspring development and function. Sixty Sprague-Dawley derived primaparous rats were administered Luminal (sodium phenobarbital) subcutaneously in doses of either 80 mg/kg, 40 mg/kg, or 0 mg/kg (saline) on Days 9-21 of gestation. The two drug groups delivered litters significantly later with evidence of increased resorption at the higher dose. The higher dose offspring were lighter in weight at birth and at adulthood, but not at weaning. The lower drug dose offspring were developmentally accelerated compared with the other two groups. Acquisition of a conditioned avoidance response (CAR) was negatively correlated with increased drug dose. In appetitive operant paradigms, saline offspring received more reinforcements on fixed ratio sequential schedules, and the lower drug dose offspring received significantly fewer reinforcements than either of the other two groups on an FR-concurrent schedule. Both groups of drug offspring were able to obtain their reinforcements with a lower expenditure of effort than the saline offspring. The higher drug dose offspring made significantly more incorrect (early and late) responses on a schedule which rewarded a delayed response (DRL).