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Biomedical subjects

H Jacobs

Publications and source records attributed to H Jacobs.

At least 127 records · Page 7Linked to original sources

Route of incorporation of alveolar palmitate and choline into surfactant phosphatidylcholine in rabbits.

Intratracheal injection of 3-day-old rabbits with radioactively labeled palmitic acid and choline results in an 8-10-fold increase in the efficiency of their incorporation into surfactant phosphatidylcholine when compared to the intravenous injection of these precursors. Based on labeling patterns in microsomal, lamellar body and alveolar wash fractions, the incorporation appears to be via normal surfactant synthetic pathways. Intratracheal injection of phospholipid precursors is useful for producing relatively high specific activity natural surfactant.

Animals↗

The significance of reutilization of surfactant phosphatidylcholine.

To assess the magnitude of reutilization of surfactant phosphatidylcholine, 68 3-day-old rabbits were injected intratracheally with a trace dose of [3H]choline-labeled surfactant mixed with [14C]palmitate-labeled synthetic dipalmitoylphosphatidylcholine. After timed kills we measured the total phosphatidylcholine associated counts/min in whole lung and alveolar wash and the specific activities of phosphatidylcholine in the alveolar wash, lamellar bodies, and microsomes isolated from the lung of each rabbit. Using a modification of the compartment analysis of Skinner et al. (Skinner, S. M., Clark, R. E., Baker, N., and Shipley, R. A. (1959) Am. J. Physiol. 196, 238-244), we found that surfactant phosphatidylcholine was reutilized with greater than 90% efficiency. The turnover time of the alveolar wash phosphatidylcholine was estimated to be 10.1 h and 9.3 h as measured by the 3H and 14C labels, respectively. From the ratios of alveolar wash-associated natural to synthetic phosphatidylcholine specific activities and from similar ratios obtained in 30 additional rabbits using [14C]choline-labeled natural surfactant and [3H]choline-labeled dipalmitoylphosphatidylcholine, we showed that phosphatidylcholine was reutilized intact rather than as component parts. Within 6 h of injection, the synthetic dipalmitoylphosphatidylcholine functioned metabolically as that administered in the form of natural surfactant.

Animals↗

Surfactant function in respiratory distress syndrome.

Airway samples from infants with respiratory distress syndrome were recovered by suction immediately after tracheal intubation for respiratory failure. The minimum surface tension of these airway samples was 27.3 +/- 3.0 dynes/cm. Surfactant with low surface tension (1.4 +/- 1.0 dynes/cm) was recovered from these samples by centrifugation; the supernatant fractions from the samples had high minimum surface tensions. The supernatant fractions contained soluble proteins that inhibited the surface tension-lowering properties of natural sheep surfactant. Similar supernatant fractions collected from infants intubated for reasons other than respiratory distress syndrome were much less inhibitory to sheep surfactant. The minimum surface tension of sequential daily airway samples from infants with respiratory distress syndrome fell progressively to 5.7 +/- 2.4 dynes/cm on the day of extubation. These results document the presence of proteins in the airways of infants with respiratory distress syndrome that inhibit the surface tension-lowering properties of surfactant.

Animals↗

Cardiovascular effects of surfactant suspensions given by tracheal instillation to premature lambs.

After delivery by cesarean section at 133-136 days gestational age, 18 lambs were supported with infant ventilators. Peak inspiratory pressure was the only ventilator setting that was changed in an attempt to normalize PCO2. The lambs were retrospectively divided into two groups based on their respiratory status before treatment. Ten lambs with PCO2 values of 38 +/- 2 mmHg (mean +/- S.E.) at 5 h of age were treated with a 15-ml suspension containing 50 mg natural sheep surfactant lipid/kg body weight. After surfactant instillation, pH fell, PCO2 increased and compliance/kg decreased transiently. Surfactant treatment did not reduce the respiratory support that these lambs required. Eight lambs with PCO2 values of 68 +/- 3 mmHg at 3 +/- 0.8 h of age responded to surfactant instillation with a decrease in PCO2 and an increase in PO2 and pH. In both groups of lambs heart rates, mean aortic pressures, and mean pulmonary artery pressures changed little after surfactant instillation. Cardiac outputs and regional blood flows measured before and after surfactant treatment were unchanged. Instillation of surfactant suspensions to premature lambs did not adversely affect cardiovascular status; however, some lambs did have a transient deterioration of lung function after surfactant instillation.

Animals↗

Surfactant phosphatidylcholine source, fluxes, and turnover times in 3-day-old, 10-day-old, and adult rabbits.

We have measured turnover times for alveolar surfactant phosphatidylcholine in rabbits at 3 and 10 days of age and in adult rabbits. To generate accurate estimates of the turnover time of surfactant phosphatidylcholine from lamellar bodies into the alveolar space, large numbers of rabbits at each age were injected with radiolabeled choline, palmitic acid, and phosphate. Phosphatidylcholine was isolated from lamellar body and surfactant fractions from each rabbit. Curves of specific activity versus time were analyzed using the Zilversmit equations for a two compartment precursor-product model. The curves for each labeled precursor at each age were consistent with the lamellar bodies being the sole precursors of surfactant phosphatidylcholine. The same equations were used to calculate turnover times for surfactant phosphatidylcholine; these were 8-10 h in 3- and 10-day-old rabbits but only 3 h in adult rabbits. From estimates of surfactant phosphatidylcholine pool sizes and turnover times, the flux of surfactant phosphatidylcholine was estimated to be 3.4 mumol/h in adult and 0.48 mumol/h in 3-day-old rabbits; however, the flux expressed/kg of body weight is 2.4 times larger in 3-day-old than in adult rabbits. Finally, the conservation of the radiolabeled precursors in phosphatidylcholine implies reutilization of phosphatidylcholine after synthesis and secretion.

Aging↗

Regulation of the relative abundances of mRNAs in hepatoma and liver.

Comparison of the polysomal poly(A)+ RNAs of normal rat liver and hepatoma (HTC) cells have shown that, while few sequences are specific to either hepatocytes or hepatoma cells, some of the abundant liver mRNAs (perhaps 20% by weight) are much rarer in the polysomal RNA from HTC cells. In contrast, these mRNA sequences are at quite similar abundances in nuclear poly(A)+ RNA from hepatocytes and hepatoma cells. The use of cloned cDNAs to measure the relative abundances of individual liver mRNA sequences in hepatocytes and HTC cells has shown that these changes occur in both directions, and indicated that post-transcriptional modulations, which are cell-type-specific and sequence-specific, play a significant role in establishing steady-state levels of polysomal poly(A)+ mRNAs. To investigate post-transcriptional regulation of mRNA abundance, a cell-free system consisting of isolated HTC-cell nuclei has been developed. This system supports the in vitro processing and/or transport of rRNA and a complex mixture of poly(A)+ RNA sequences which resembles polysomal poly(A)+ RNA from HTC cells. The pattern of relative abundances of the sequences in released poly(A)+ RNA is intermediate between that of polysomal and nuclear poly(A)+ RNAs, and indicates that some degree of sequence-specific selection of processing and/or transport is maintained in isolated nuclei. Sequence-specific selection of individual poly(A)+ RNA sequences in vitro has been detected with cloned cDNAs.

Animals↗

Continuous wave carbon dioxide treatment of balanitis xerotica obliterans.

Herein is presented the first case of balanitis xerotica obliterans treated successfully by carbon dioxide-continuous wave (CW-CO2) laser vaporization. This method appears to be a safe addition to other well-known treatment modalities, offering minimal postoperative discomfort, preservation of anatomic landmarks and function, and excellent cosmetic results.

Adult↗

Some guidelines in the treatment of urethral condylomata with carbon dioxide laser.

Some guidelines for the use of carbon dioxide laser treatment of urethral condylomata are presented. Carbon dioxide laser treatment was accomplished successfully in 22 patients with distal urethral and meatal condylomata. Of the patients 86.6 per cent responded to a single laser treatment and 13.4 per cent had evidence of persistence or new growth that required repeat therapy. Meatotomy was required in 4 patients for adequate exposure. This form of therapy appears to be safe for eradication of superficial mucosal lesions and can be used either as a first choice of treatment or as an adjunct in those patients not responding to other well known conventional treatment modalities.

Adolescent↗

Premature lambs rescued from respiratory failure with natural surfactant: clinical and biophysical correlates.

Thirty-four Western mixed breed lambs were delivered prematurely at 120 days gestational age (term = 150 days). Four lambs were sacrificed at birth, and four lambs were sacrificed with the onset of respiratory failure (PCO2 greater than 80 torr) at about 30 min of age. The remaining lambs were treated by tracheal instillation with 50 mg of natural sheep surfactant lipid/kg body weight. These lambs were sacrificed 10 min, 40 min, 1.5 h and 3 h after surfactant treatment. Frequent blood gas and compliance measurements documented the clinical responses of the lambs. Lungs from treated lambs showed large increase relative to untreated lungs in air volumes as assessed by pressure-volume curves and by histology. However, the pressure-volume and histologic measurements did not distinguish between the posttreatment groups of lambs. Minimum surface tensions of alveolar washes fell from greater than 30 dynes/cm to 6.3 dynes/cm 10 min after treatment and again rose to 21.6 dynes/cm within 3 h. Minimum surface tensions correlated well with the PO2 values but not with the PCO2 values measured before sacrifice. The combination of dilated distal airways and atelectasis resulted from increasing surface tensions with time and mechanical ventilation and may explain the clinical deterioration without much change in the volume of gas within the airways.

Animals↗

Changes in the amount of lung and airway phosphatidylcholine in 0.5-12.5-day-old rabbits.

Newborn rabbits delivered spontaneously at term and cared for by the mothers were studied from 0.5 to 12.5 days of age. Curves are constructed to describe the changes in weight, lung and alveolar wash phosphatidylcholine and saturated phosphatidylcholine, and lung protein. The curves are complex and non-linear. However. expressing the increases in lung and alveolar wash phosphatidylcholine and saturated phosphatidylcholine pool sizes relative to animals weight results in a decreasing linear relationship from 0.5 to 12.5 days of age. By 12.5 days the ratios of lung phosphatidylcholine and saturated phosphatidylcholine to weight approximate the ratios measured for adult rabbits. The ratios of saturated to total phosphatidylcholine in the alveolar washes and lungs remained invarient throughout the study period.

Age Factors↗

Rapid superpulse carbon dioxide laser treatment of urethral condylomata.

Complete eradication of urethral condylomata was accomplished by rapid super-pulsed carbon dioxide laser in 4 patients. Minimal postoperative discomfort and lack of stricture formation indicate that this new modality is an advantageous, fast, and secure method of management of intraurethral condylomata, and substantiated by our previous experimental reports.

Carbon Dioxide↗

Sequential treatments of premature lambs with an artificial surfactant and natural surfactant.

To test an artificial surfactant in vivo, six 120-d gestational age lambs were treated at birth with a mixture of a 9:1 M ratio of [14C]dipalmitoyl phosphatidylcholine (DPC) and phosphatidylglycerol at a dose of 100 mg DPC/kg. Nine other lambs were not treated. The mean PO2 values of the lambs treated with artificial surfactant were 65.7 +/- 11 mm Hg vs. 24.8 +/- 1.6 mm Hg for the untreated lambs (P less than 0.001). All lambs then were treated with 50 mg/natural surfactant lipid per kg, which promptly improved PO2 in all lambs. The PO2 values of those lambs previously treated with artificial surfactant remained greater than 100 mm Hg for 2.5 +/- 0.5 h vs. 0.9 +/- 0.3 h for lambs untreated with artificial surfactant (P less than 0.01). The pH and PCO2 values were not strikingly different between the two groups of lambs. Airway samples taken from lambs treated with artificial surfactant before treatment with natural surfactant had minimal surface tensions of 32 +/- 2.9 dyn/cm, whereas the artificial surfactant reisolated from these samples by centrifugation had minimum surface tension of 0 dyn/cm. The minimum surface tension of artificial surfactant was inhibited by fetal lung fluid from the premature lambs, whereas the minimum surface tension of natural surfactant was much less sensitive to inhibition. Artificial surfactant did not improve the pressure-volume characteristics of unventilated premature lung, whereas natural surfactant did. The change in specific activity of [14C]DPC following treatment with natural surfactant indicated that approximately 50% of the DPC initially administered was no longer associated with the airways.

Animals↗

Post-transcriptional regulation of messenger abundance in rat liver and hepatoma.

Saturation hybridisation with labelled single-copy DNA shows that polysomal poly(A)+ RNA of rat liver and of a minimum-deviation rat hepatoma cell-line (HTC) have similar total complexities and that few sequences are specific to either cell-type. Hybridisation kinetics of polysomal cDNAs with template and heterologous cell RNAs indicate that a proportion of liver messengers are at greatly reduced abundance in the hepatoma, but not the converse. Hybridisations using fractionated cDNAs enriched for abundant polysomal sequences confirm these findings: on average, abundant liver mRNAs are about 100-fold rarer in hepatoma, whereas abundant hepatoma mRNAs are only 5-fold rarer in liver. This pattern is also implied by cell-free translation of polysomal poly(A)+ RNAs. The reactions of total and fractionated polysomal cDNA probes with poly(A)+ nuclear RNA indicate that there is much less disparity in abundance of these sequences at nuclear level, implying that the differences arise, at least in part, post-transcriptionally. We interpret the altered mRNA abundances in the hepatoma in terms both of its decreased functional specialisation and its ability to proliferate.

Animals↗

Methanol poisoning: a clinical and pathological study.

We report 2 survivors of severe methanol poisoning who developed, apart from blindness, a Parkinson-like extrapyramidal syndrome characterized by reduced initiative, poor voice volume, masked facies, mild tremor, rigidity, and bradykinesia. Both patients were mildly demented and 1 had hyperreflexia and bilateral Babinski responses. Computed tomographic scans in both patients demonstrated bilateral symmetrical infarction of the frontocentral white matter and putamen. Electromyography in 1 patient showed extensive denervation, mainly involving the legs, but normal motor conduction velocities. L-Dopa administered to the more severely affected patient had no effect on the parkinsonian features. Autopsy revealed cystic resorption of the putamen and the frontocentral subcortical white matter in additon to widespread neuronal damage throughout the cerebrum, cerebellum, brainstem, and spinal cord.

Adult↗