Arterial blood gases in acute pulmonary edema.

Arterial blood gas and pH measurements in 82 patients with acute pulmonary edema of cardiogenic origin entering the emergency department varied widely and were unpredictable using clinical examination. The mean arterial oxygen tension (PaO2) measured in 71 patients breathing room air was 59 mm Hg. Fourteen of the 82 patients were acidemic; 35, alkalemic and 33 had a pH in the normal range. The acidemic group had markedly lower PaO2, all under 60 mm Hg. Oxygen and furosemide were used in all cases and effectively corrected the hypoxia and reduced pulmonary congestion. Other drugs used included aminophylline (14 patients), morphine sulfate (9 patients) and digoxin (3 patients). Five of the nine patients who received morphine were hypercarbic initially but the CO2 retention did not worsen. No patient died during the initial 48 hours. This study reiterates the importance of directing therapy at ventilatory and cardiac abnormalities and points out the value of arterial blood gas monitoring to assess the initial status, monitor the patient's course, and to select drug therapy.


The effectiveness of mobile coronary care in a nonurban area.

During an eight-month period 225 patients in a nonurban area (65,000 population) received care from a mobile coronary care unit (MCCU) staffed by coronary care nurses from the hospital coronary care unit. There were 29 (13%) deaths. One hundred and twenty-six of the patients were eventually diagnosed as coronary disease cases (including the 29 deaths) while 99 were released with the noncardiac diagnoses. The provision of definitive emergency medical care prior to hospitalization resulted in eight lives definitely saved (three "long-term saves" and five "short-term saves") and seven lives possibly saved (six long-term saves and one short-term save). On an annual basis, per 100,000 population, these results would account for 18.5 definite saves (6.9 long-term saves and 11.5 short-term saves) and 16.2 possible saves (13.9 long-term saves and 2.3 short-term saves).


Carbon monoxide intoxication: a review of 14 patients.

In 14 cases of carbon monoxide poisoning, medical records were available for retrospective review in which blood samples for carboxyhemoglobin (COHgb) were obtained. Twelve victims (86%) were overcome while at work. Correlation of the clinical picture and COHgb saturation was not always possible although hypertension was not uncommon initially. On follow-up only three patients were mildly hypertensive. Skin or mucous membrane color changes were difficult to detect. Three cases are presented to illustrate factors in the diagnosis and possible sequelae.


Specialized blood filters and fresh whole blood.

Platelet counts and platelet functions were determined in fresh whole blood before and after it passed through two types of specialized transfusion filters. Both filters were capable of trapping 20% to 40% of the functional platelets, necessary for hemostasis, especially if heparin was used as the anticoagulant. When fresh whole blood is needed to treat the bleeding patient who has already received massive blood transfusions, these specialized filters should probably not be used.


Blind defibrillation outside the hospital.

Blind defibrillation, defibrillation of an unconscious, pulseless adult without electrocardiographic verification of arrhythmia, allows early definitive treatment of cardiac arrest victims. Basic EMT-As have the ability to perform blind defibrillation in a prehospital setting, and place an esophageal obturator airway. When basic EMT-As are performing blind defibrillation, there should be a standard operating procedure involving diagnosis, defibrillation, CPR and re-evaluation.


Rotatory subluxation of the atlas on the axis.

The clinical findings of rotatory subluxation of the atlas are subtle and x-ray films involving the upper cervical segment are difficult to interpret. Nevertheless, patients with rotatory subluxation must be separated from those with "stiff necks," for they require hospital admission for cervical traction if complications are to be avoided. A case is reported and management and diagnosis are reviewed.


Permanent ileostomy without external appliance: Kock internal reservoir (pouch) operation.

Employing a surgical technique described by Dr. Nils Kock of Göteborg, Sweden one can create a continent ileostomy beyond an internal reservoir of ileum for patients who have had total proctocolectomy. This operation is designed to obviate the necessity for wearing an external appliance. Instead, the patient introduces a catheter through the ileostomy into the reservoir of ileum three or four times daily and evacuates it in a convenient manner. Our experience with seven patients, as well as a useful opertive variation of our own, is described. In six patients the procedure was carried out at the time of proctocolectomy. Currently six of the seven patients function without an appliance. Two of the seven had serious postoperative complications which were associated with the pouch. While a number of physical and emotional advantages are ascribed to the procedure, the specific hazards of the complex surgery, the extra time consumed daily in emptying the reservoir, and the necessity for further surgery if the pouch fails to function in a satisfactory manner must be balanced against them. Over the short term, the experience of our patients with this operation has been favorable. Larger series have been reported by Dr. Kock and by Dr. Beahrs at the Mayo Clinic. While 80% of their patients have had satisfactory eventual outcomes, a larger number of secondary operations and an ultimate 20% incidence of unsatisfactory results dictate the necessity for a guarded approach to this procedure.


Free fatty acid metabolism in the forearm at rest: muscle uptake and adipose tissue release of free fatty acids.

Free fatty acid (FFA) metabolism in forearm skeletal muscle at rest was studied during continuous intrabrachial arterial ininfusion of [1-14C] oleic acid in 14 normal subjects in the postabsorptive state. Total oleic acid uptake by muscle accounted for at least 65% and perhaps as much as 86% of the measured O2 consumption. The respiratory quotient (0.74) indicated predominant oxidation of lipid. Glucose was a minor substrate for oxidation. Concentrations of six individual free fatty acids were measured in arterial (A), deep venous (DV), and superficial venous (SV) plasma in 25 subjects. There were positive A-DV differences, reflecting net muscle uptake, for each FFA. The extraction ratio (A-DV)/A was greatest for oleic acid. Output of each free fatty acid from subcutaneous adipose tissue was proportional to its arterial concentration, except for stearic acid. There was no stearic acid output. Correction of (A-DV)/A to account for contribution of perimuscular adipose tissue to FFA in DV led to the conclusion that oleic acid was preferentially extracted from arterial blood by forearm muscle. It accounted for 51% of the total FFA uptake, although it comprised only 43% of total FFA in arterial plasma. Total FFA uptake by muscle was more than sufficient to account for all of the measured O2 consumption, suggesting that some of the extracted FFA may be stored in muscle for oxidation at a latter time.


Hypothyroidism after x irradiation to the neck: three case reports and a brief review of the literature.

Three patients who developed hypothyroidism after x irradiation to the neck are presented. The first two cases demonstrate that patients can develop clinical and chemical hypothyroidism after a very short interval following radiotherapy. Hypothyroidism developed in the first patient in the absence of surgical manipulation of the neck, or a large iodine load 4 months after receiving 6800 rad of x-ray therapy to his neck for carcinoma of the larynx. The second patient developed hypothyroidism approximately 6 months after his radiotherapy for carcinoma of the esophagus. Both of these patients demonstrated high titers of serum antithyroid antibodies. A third patient with Hodgkin's disease did not manifest clinical symptoms and signs of hypothyroidism until 6 years after radiation therapy. These cases demonstrate the variability of onset of hypothyroidism after radiotherapy and emphasize the need for careful evaluation of thyroid function before and after neck irradiation.


What becomes of medical students: the dark side.

In the cohort of 1337 former Johns Hopkins medical students from the classes of 1948 through 1964, there were 1248 graduates and 89 nongraduates. In follow-up studies of this cohort, 49 subjects, 3.1% of the graduates and 11.2% of the nongraduates, have been found to have died prematurely. Incipient mental illness and emotional disturbance appear to have contributed substantially to academic failure, poor performance during and after medical school, and premature death. These findings underscore the need for learning to identify and help medical students who are especially vulnerable to stress. Such insights would contribute to the prevention of premature disease and death, not only from mental illness but from other disorders.


Distribution of endogenous albumin in the rat glomerulus: role of hemodynamic factors in glomerular barrier function.

Using an ultrastructural immunoperoxidase technique, the distribution of endogenous albumin in the rat glomerulus was delineated under normal and abnormal hemodynamic conditions. Superficial glomeruli in anesthetized Munich-Wistar rats were rapidly fixed in situ by applying glutaraldehyde to the renal surface. Fixed tissue slices were treated with anti-rat albumin Fab fragments conjugated to horseradish peroxidase (HRP), and were then subjected to the Graham-Karnovsky ultrastructural peroxidase localization procedure. During normal blood flow, dense reaction product specific for albumin was largely confined to the glomerular capillary lumen and endothelial fenestrae, with only small amounts detectable in the lamina rara interna, and none deeper in the basement membrane (GBM) or in the urinary space. If cortical tissue was subjected to routine immersion fixation, or if fixation was performed in situ after ligation of the renal artery, reaction product was detected throughout the GBM and in the urinary space. If fixation was performed in situ after ligation of the renal artery and vein (or artery, vein and ureter), reaction product was found in the GBM and, in very large amounts, in the urinary space. If blood flow was restored for ten minutes after five minutes of renal pedicle (artery and vein) occlusion, the distribution of albumin returned to normal. Thus, glomerular barrier function depends upon the maintenance of normal blood flow conditions.


Tubular chloride transport and the mode of action of some diuretics.

The renal diluting segment (thick ascending limb of Henle's loop) reabsorbs sodium chloride in excess of water and is responsible for dilution of the urine as well as reabsorption of a large fraction of the salt present in the glomerular ultrafiltrate. In this segment, there is active reabsorption of chloride which causes the voltage to be positive in the tubule lumen. Most, if not all, of the sodium transport is passive, driven by the voltage. Three major diuretic drugs (mersalyl, furosemide and ethacrynic acid) act in the lumen of the diluting segment to inhibit active chloride transport, not sodium transport as previously believed. This specific action on chloride transport may explain how these drugs are able to inhibit salt transport in the kidney while having so little effect on the electrolyte transport processes elsewhere in the body.


Effect of intraluminal pressure on the ultrastructure and protein transport in the proximal tubule.

Proteins filtered in the kidney are generally considered to be catabolized by the renal lysosomes, but it has also been suggested that some protein may pass the tubule wall intact via the intercellular spaces. To examine the latter possibility, electron-dense tracers were in one part of the study injected retrograde into the kidney of living flounders and in another part by micropuncture directly into the tubule lumen of isolated flounder kidney tubules incubated in vitro. In both cases disruptions in the tubule wall were demonstrated and this was shown to be associated with the passage of tracer into the lateral intercellular spaces. From the in vitro studies it was further shown that only when the intraluminal pressure is increased do tracers pass into the intercellular spaces and they do so via the disruptions in the tubule wall. It is concluded that no passage of tracer occurs at intraluminal pressures in the physiological range.


Functional segmentation of the rabbit distal tubule by microdetermination of hormone-dependent adenylate cyclase activity.

Rabbit distal convoluted tubules (DCT) microdissected from collagenase-treated kidneys were observed to contain up to four portions of a different appearance under stereomicroscopic examination: (1) a DCTa portion (generally very short), located right after the macula densa (MD) and resembling the portion of the limb (CAL) located before the MD; (2) a constant, "bright" portion, DCTb; (3) a constant, "granular" DCTg portion which, in most DCT, is connected to a portion of the collecting tubule of a similar "granular" appearance (CCTg); (4) many DCT having contacts with the kidney capsule in the superficial cortex were observed to contain an additional portion of a "light" appearance, DCTl, resembling the portion of the collecting tubule (CCTl) to which these superficial DCT are always branched. The hormone-dependent adenylate cyclase (AC) contained in these different portions was investigated by sectioning microdissected distal structures into successive samples according to the above-mentioned criteria, and by measuring with the help of a previously described micromethod, the enzyme activity contained in each single sample under one of the following conditions: control, parathyroid hormone. (PTH l U/ml), vasopressin, (AVP 10(-6)M), isoproterenol (10(-6)M), fluoride (5 X 10(-3)M). Highly significant and reproducible AC stimulations by these hormones were obtained for the following portions, respectively: DCTa, DCTg and CCTg with PTH; DCTl and CCTl with AVP; DCTg, CCTg and CCTl with isoproterenol. From these data, it is concluded that (a) the distal convoluted tubule can no longer be regarded as a single well-defined functional structure; (b) DCTa is actually a short CAL portion extending beyond MD, (c) DCTg and CCTg are two portions of a same functional segment; (d) similarly, DCTl belongs to the functional segment mainly constituted by CCTl; and, finally, (e) DCTb is the only functional segment which is entirely located in the distal convoluted tubule, i.e., included between the macula densa and the first branching with another tubule.


Dialysis costs: results of a diverse sample study.

A study of dialysis costs in five major dialysis centers throughout the United States was conducted in 1973. When available, home, home training, limited care, satellite and in-hospital-full-care dialysis were included. The study's objective was to determine the cost per dialysis for each separate dialysis modality. All costs associated with the dialysis procedure were included. Using a uniform methodology, costs were collected on four care levels which vary significantly from each other in the use of direct labor. They are as follows: home, home care training, limited care and full care. Costs were also segregated into five expenditure categories: personnel, supplies, travel, equipment and other. They study was designed to show the range of costs in five "representative" centers throughout the country, but not to provide statistical "average" of dialysis costs. Cost per dialysis ranged from $33 to 66 for the home patient group, $100 to 116 for limited care, $144 to 172 for in-hospital and $146 to 259 for the home training units.


Hypertension in terminal renal failure.

Inverse interrelations between plasma renin activity and exchangeable sodium or blood volume were found in both normotensive (N = 23) and hypertensive (N =29) hemodialysis patients (r= 0.47; P less than 0.005); however, mean plasma renin for any given sodium/volume state was at least two-fold higher in hypertensive than in normotensive hemodialysis patients or normal subjects (N =31). In the hemodialysis patients, blood pressure correlated weakly but significantly with the products of circulating renin and exchangeable sodium (r=0.37; P less than 0.005) or blood volume (r = 0.29; P less than 0.05). Multiple regression analysis including duration of previous hypertension as the second independent variable increased these correlation coefficients to 0.44 and 0.42, respectively. This suggests that hypertension in endstage kidney disease is often associated with resetting of the body sodium/fluid=renin feedback mechanism. Inappropriately increased plasma renine activity relative to the body sodium/volume state as well as high blood pressure-induced vascular changes may play important complementary roles, but it appears evident that additional mechanisms are also operative in maintaining end-stage renal hypertension.


Bartter's syndrome with hyperplasia of renomedullary cells: successful treatment with indomethacin.

During treatment with indomethacin in a patient with Bartter's syndrome, hypokalemia, high plasma renin concentration, hyperaldosteronism and decreased sensitivity to angiotensin infusion were corrected. A particular finding in the renal biopsy specimen was a marked hyperplasia of renomedullary interstitial cells which had characteristics similar to the cells known to produce renal prostaglandins. The hypothesis is formultated that the primary defect in this syndrome is related to hyperplasia of renomedullary interstitial cells and inappropriate release of renal prostaglandins giving rise to decreased sodium reabsorption, volume depletion and hypersecretion of renin and aldosterone.


Potassium secretion by the decending limb or pars recta of the juxtamedullary nephron in vivo.

Potassium reabsorption by the juxtamedullary nephron up to the hairpin turn was studied by the micropuncture technique in the exposed renal papilla of rats. In 18 nondiuretic rats, the fraction of filtered potassium remaining at the end of the desdending limb averaged 113 +/- 9%, indicating either that potassium  is not reabsorbed by the juxtamedullary proximal tubule and descending limb or that potassium is reabsorbed and secreted in those segments. Furosemide, a drug which inhibits NaCl reabsorption in the ascending limb downstream from the descending limb, significantly decreased the potassium remaining at the end of the descending limb from 106 +/- 12 to 72 +/-11% in seven rats. Benzolamide, a drug which inhibits reabsorption of NaHCO3 and water in the proximal tubule upstream from the descending limb significantly increased the potassium remaining from 103 +/- 13 to 177 +/- 32% in eight rats. These findings support the hypothesis that in the rat, potassium is normally reabsorbed by the proximal convoluted tubule and secreted in the pars recta or descending limb of the juxtamedullary nephron.


Bone histology in incipient and advanced renal failure.

Quantitative bone histology (micromorphometry of undecalcified sections, analysis under polarized light; fluorescence microscopy with tetracycline double labelling) as well as serum and urinary chemistry (creatinine clearance, parathyroid hormone, ionized Ca, bone phosphatase, pH), were studied in 50 patients with incipient to advanced (glomerular filtration rate, 80 to 6 ml/min x 1.73 m2 renal insufficiency. In incipient renal failure, indirect evidence of parathyroid hormone excess was found in the skeleton (empty osteoclastic lacunae, woven osteoid). Osteoclastic surface resorption was  abnormally high when GFR fell below 50ml/min x 1.73 m2. With the tetracycline double-labelling technique, a mineralization defect was demonstrable in many but not all patients.


Analysis and outcome of 1063 patients trained for home hemodialysis.

Between 1967 and 1973, 12 home dialysis training centers (HDTC), under contract to the health Resource Administration, Department of Health, Education, and Welfare, reported training 1063 patients. Mean training time was 69 days; mean patient age was 40 yr with a range of 12 to 75 yr. Survival rates were 87% at one year, 74% at two years, 62% at three years, 54% at four years and 52% at five years. Male to female ratio was 3.2; there was no significant survival difference between sexes. Patients under 50 yr of age had significantly greater survival than did patients 50 yr and older. A "good" health status classification, defined by activity tolerance, signs and symptoms at the beginning of home dialysis, was associated with more favorable survival than were lower health ratings. Patients with glomerulonephritis, pyelonephritis and polycystic disease had better survival than did patients with diabetic, hypertensive and other renal disease etiologies. Although 51% of the patients lived 50 to 400 or more miles from the HDTC, their survival was not different from patients living less than 50 miles from the HDTC. Survival rates for patients with less than ten years of education were not significantly different from those with formal education as high as the university graduate level. Forty-seven percent of the patients were restored to full activity. These survival results are comparable with those reported for other modes of dialysis and transplantation and indicate that home dialysis is an acceptable form of therapy for a variety of patients.


Pathogenesis of the glomerulopathy associated with renal infarction in rats.

The present studies were designed to characterize the extent and pathogenesis of the glomerular lesions which occur in the viable portion of the kidney following partial renal infarction in rats. Control rats with two normal kidneys had a mean blood pressure of 112 mm Hg, minimal proteinuria and no glomerular pathology on light (LM), electron (EM) or immunofluorescence microscopy (IFM). Rats with two-thirds infarction of one kidney (stage II) became hypertensive, although less than 4% of the glomeruli from either kidney were abnormal. Rats with two-thirds infarction of one kidney and contralateral nephrectomy (stage III) developed proteinuria and hypertension whether fed a normal, low or high Na+ diet. By light microscopy 37% of glomeruli were abnormal 28 days after partial infarction and contralateral nephrectomy and thereafter the percent of abnormal glomeruli increased. Detectable amounts of immunoglobulin and complement (C3) were present in kidneys of stage II or III rats but were always accompanied by more extensive albumin and fibrin deposits. Basement membrane deposits characteristic of immune complexes were not seen on EM. Administration of antihypertensive medication to stage III rats significantly lowered blood pressure and reduced the number of abnormal glomeruli on LM; however, IFM abnormalities remained prominent. Platelet thrombi seen by EM and abundant glomerular fibrin deposits seen on IFM suggested that coagulation mechanisms may be prominent in the pathogenesis of the renal lesion. Heparin-treated stage III rats had significantly lower blood urea nitrogen concentrations, blood pressures and proportion of abnormal glomeruli although glomerular deposition of serum proteins was still present on IFM. These observations suggest that this glomerulopathy is initiated by an unknown agent(s) which increased capillary permeability. This lesion progresses via thrombotic mechanisms which are prevented by heparin administration.


Pharmacokinetics of gentamicin during peritoneal dialysis in children.

The pharmacokinetics of gentamicin were examined on two occasions using intravenous and intraperitoneal routes in five children undergoing intermittent peritoneal dialysis for chronic renal failure. Serum, urine and dialysis fluid (DF) were assayed microbiologically for gentamicin and the data were subjected to computer analysis using equations evolved for a two-compartment model which considered the bi-directional flux of the drug. Following i.v. injection of 1 mg/kg of gentamicin, the apparent volume of distribution averaged 23% (range, 13 to 36%) of body wt (similar to normal), the mean half-life was 21 hr (range 9 to 37 hr; normal, 2 hr) and the peritoneal clearance averaged 4.0 ml/min/m2 (range, 1.2 to 7.0 ml/min/m2). During peritoneal administration of gentamicin (15 mg/liter of DF, 0.7 liters/m2 administered in each cycle over 9 to 12 cycles), serum concentrations increased towards extrapolated steady-state levels which averaged 42% (range, 25 to 68%) of DF concentrations. The mean renal clearance of gentamicin was only 1.6 ml/min/m2 while total body clearance ranged from 2.3 to 8.0 ml/min/m2 mostly occurring by a variable degree of dialysance. Peritoneal clearances and half-lives of gentamicin were similar in each patient following either treatment mode. The appreciable variability in gentamicin pharmacokinetics among adolescent patients with renal insufficiency necessitates dosage adjustments based on measurements of serum concentrations.


Effect of intraluminal bicarbonate and chloride on fluid absorption by the rat renal proximal tubule.

In order to study mechanisms of fluid transport in the rat renal proximal convoluted tubule, the effects of large variations in intraluminal HCO3- and Cl- concentrations were measured by microperfusion techniques. No differences in rates of fluid transport were found when intraluminal HCO3- was varied from 4 to 30 mEq/liter and Cl- from 146 to 120 mEq/liter. Inhibition of H+ secretion with benzolamide had no effect on fluid absorption when little or no HCO3- was present in the lumen, but did reduce fluid transport when 25 mEq of HCO3- was present. If several different mechanisms are responsible for proximal fluid transport, such as nonelectrogenic active NaHCO3 transport, passive chloride diffusion and active sodium transport linked to H+ secretion, the above observations imply that they all operate at approximately the same rate, since the dominant driving force would have been different with each perfusion solution. The data seem more compatible with the view that active sodium transport is the major driving force for fluid absorption in the proximal tubule, that this is not linked to H+ secretion and that anions modify the rate of absorption only to the degree that they are able to accompany sodium across the epithelium. An additional observation was that absorption of isotonic NaCl was very slow in short segments of tubule, as compared to HCO3--containing perfusion solutions. Although the mechanism is uncertain, these data suggest that a finite amount of intraluminal HCO3- is necessary for optimal proximal fluid transport.


Skeletal resistance to the calcemic action of parathyroid hormone in uremia: role of 1,25 (OH)2 D3.

Studies were carried out to investigate the role of 1,25(OH)2D3 in the skeletal resistance to the calcemic action of parathyroid hormone. The change in serum calcium after the intravenous infusion of 2 U of parathyroid extract (PTE)/kg body wt/hr for eight hours was evaluated in thyroparathyroidectomized (T-PTX) dogs before, and one, two and three days after, induction of uremia by bilateral ureteral ligation (11 dogs) or by bilateral nephrectomy (8 dogs). In another six nephrectomized and T-PTX dogs, 0.68 ug of 1, 25 (OH)2D3/day was given on the day of nephrectomy and for two days thereafter. Serum creatinine in each day of the study was not different among the three groups. The study also included the evaluation of the effect of sham operation (five dogs) and the administration of 1,25 (OH)2D3 to dogs with normal renal function (four dogs) on the calcemic response to PTE, as well as the reproducibility of such a response in the same animal. The results showed that 1) the calcemic response to PTE was markedly impaired after one day of bilateral ureteral ligation or nephrectomy, but the impairment was more severe after nephrectomy; 2) the calcemic response to PTE after two or three days of bilateral ureteral ligation was similar to that seen at one day after nephrectomy; 3) 1, 25 (OH)2D3 partially restored the calcemic response to PTE in the nephrectomized animals to levels similar to those seen after one day of bilateral ureteral ligation; 4) sham operation did not affect the response to PTE, and repeated infusion of PTE produced similar changes in the concentrations of serum calcium. The data indicate that (a) a deficiency of 1,25 (OH)2D3 is at least partly responsible for the skeletal resistance to the calcemic action of PTH in uremia; (b) uremia, per se, may also contribute to this phenomenon; and (c) the kidney after one day of complete bilateral ureteral ligation may still produce 1,25 (OH)2D3, but this ability is compromised after two days of ureteral obstruction.


Role of the efferent arteriole in glomerular hemodynamics of superficial nephrons.

Hemodynamic pressure in glomerular capillaries (GCP) and in first order peritubular capillaries (EAP) in superficial nephrons of mutant Wistar rats with surface glomeruli was measured by micropuncture with a servo-nulling device in the following conditions: 1) control;2) norepinephrine infusion (NE); 3) epinephrine infusion (E): 4) dopamine infusion (D); 5) hemorrhagic hypotension (HH); 6) HH + NE; 7) HH + E; 8) HH + D; 9) acute hypertension secondary to bilateral cervical vagotomy and occlusion of both common carotid arteries. BP was also recorded. Both GCP/BP and EAP/GCP ratios averaged 0.40 in control conditions, but only the EAP/GCP ratio remained constant in all conditions under study, indicating that approximately 60% of the hydrostatic pressure in glomerular capillaries is constantly dissipated by the efferent arteriole. When all values of EAP were plotted against the respective values of GCP, a liner relationship was detected (r=0.843). These results indicate that changes of pressure in the first order peritubular capillaries of superficial nephrons are merely secondary to changes in glomerular capillary pressure.


Bicarbonate reabsorption in chronic renal failure.

Bicarbonate reabsorption was studied in dogs before and after induction of renal failure, produced by infarction of one kidney and removal of the contralateral kidney. Glomerular filtration rate and renal plasma flow decreased to 21 and 37% of control values, respectively. Fractional potassium excretion and fractional phosphate excretion increased significantly. Volume expansion resulted in a significant decrease of bicarbonate reabsorption in both control and uremic groups. At comparable levels of fractional chloride excretion, bicarbonate reabsorption was significantly higher in renal failure than in control animals. In the second group of dogs, following induction of renal failure, sodium bicarbonate was given orally in an amount sufficient to neutralize endogenous acid production. Bicarbonate reabsorption was again significantly higher than in control animals. Thyroparathyroidectomy had no effect on bicarbonate reabsorption. Absolute bicarbonate reabsorption and sodium reabsorption were lineraly related in control animals and in those in renal failure; the ratio of absolute bicarbonate reabsorption/abolute sodium reabsorption was significantly higher in renal failure than in control. These data demonstrate that renal failure is associated with enhanced bicarbonate reabsorption which is not related to the state of extracellular volume, the need to increase acid excretion or the concentrations of parathyroid hormone. These findings suggest that there are additional unknown factors controlling bicarbonate reabsorption in renal failure.


Alterations of renal function during dietary-induced hyperuricemia in the rat.

Hyperuricemia was induced in rats ingesting a diet supplemented with 2 1/2+ uric acid and 5% oxonic acid (an inhibitor of hepatic uricase activity). After seven days, inulin clearance (CIn) and superficial nephron glomerular filtration rate (SNFR) were significantly lower than values recorded in healthy rats (CIn:0.94 +/- 0.10 vs. 3.61 +/- 0.13 ml/min/kg of body wt; SNFR: 54.9 +/- 3.2 vs. 129.7 +/- 6.7 nl/min/kg of body wt). Filtration rate reduction was accompanied by an increased concentration of urate in renal tissue. Gross examination of the kidney revealed the presence of whitish streaks containing negatively birefringent crystals throughout the medulla and papilla. Histological examination revealed dilatation of the collecting ducts with flattening of the epithelium and intraluminal crystalline deposits. Intraluminal hydrostatic pressure was markedly higher than that observed in healthy rats in both proximal (21.5 +/- 1.7 vs. 11.4 +/- 0.3 mm Hg) and distal convoluted tubules (20.3 +/- 2.0 vs. 7.6 +/- 0.5 mm Hg). In another group of rats ingesting a similar diet, CIn was reduced to 1.49 +/- 0.20 ml/min/kg of body wt. Partial or complete restoration of CIn toward normal was effected within seven additional days by the oral ingestion of a large volume of an alkali solution (CIn:2.63 +/- 0.44 ml/min/kg of body wt) or by the cessation of treatment with oxonic-uric acid (CIn: 4.70 +/- 0.28 ml/min/kg of body wt). These results demonstrate that oxonic/uric acid-induced hyperuricemia is accompanied by severe filtration rate reduction, and they suggest strongly that intraluminal obstruction, via the deposition of uric acid, plays an important role in its pathogenesis.


Acute effects of parathyroid hormone on proximal bicarbonate transport in the dog.

Re-collection micropuncture and simultaneous clearance studies were performed in thyroparathyroidectomized (TPTX) dogs to evaluate the effects of the acute administration of parathyroid hormone (PTH) on bicarbonate reabsorption. The i.v. administration of PTH from 74 to 94 U/hr reduced proximal fractional reabsorption (FRHCO3) from 0.28 +/- 0.03 to 0.14 +/- 0.03 (P less than 0.005) and absolute bicarbonate reabsorption (THCO3) from 556 +/- 126 to 255 +/- 73 pmoles/min (P less than 0.05), whereas there were no changes in PCO2 (37.0 +/- 1.4 leads to 37.2 +/- 1.4 mm Hg, P greater than 0.90), plasma bicarbonate (PHCO3) (18.5 +/- 0.4 leads to 18.3 +/- 0.4, P less than 0.60), single nephron glomerular filtration rate (102.2 +/- 15;9 leads to 90.1 +/- 10.3 nl/min, P greater than 0.40), serum ultrafilterable phosphate concentration (SUFp) (1.71 +/- 0.13 leads to 1.83 +/- 0.12 mmoles/liter, P greater than 0.25), or serum ultrafilterable calcium (SUFCa) (1.85 +/- 0.05 leads to 1.88 +/- 0.05 mEq/liter, P greater than 0.60). PTH also reduced proximal fractional fluid (and sodium) reabsorption (0.40 +/- 0.04 leads to 0.28 +/- 0.08, P less than 0.05) while TFHCO3 did not change (20.5 +/- 0.4 leads to 20.8 +/- 0.4 mmoles/liter) indicating a rejection of bicarbonate proportional to the inhibition in tubular fluid transport. The invariable reduction in proximal bicarbonate reabsorption did not uniformly result in an increased urinary bicarbonate concentration.


Effect of blockade of angiotensin II on blood pressure, renin and aldosterone in cirrhosis.

1-Sar-8-ala angiotensin II (saralasin) was infused intravenously in graded doses of from 0.1 to 10 mug/kg/min to five patients with cirrhosis and ascites after three days of restricted sodium intake. In each patient blockade of AII by saralasin produced a marked fall in blood pressure, a rise in plasma renin activity (PRA) and plasma renin concentration (PRC) and, in four of the five, a fall in plasma aldosterone (PA). The rise in PRA and PRC correlated poorly with changes in blood pressure. The effects of saralasin rapidly reversed after cessation of the infusion. Plasma volume was normal or high in each case. Three patients were mildly hypotensive in the control state, and all five were resistant to the pressor effect of infused AII. After three days of salt loading, the above effects of saralasin were diminished but not abolished. In four normal subjects, after salt depletion, saralasin infusion induced qualitatively similar but much smaller changes in blood pressure, PRA and PRC. In two cirrhotic patients without ascites, after salt depletion, saralasin infusion caused a rise in blood pressure with no significant changes in PRA, PRC or PA. These results provide evidence that in patients with cirrhosis and ascites circulating AII is active in support of blood pressure, in direct suppression of renal renin release, and in stimulation of aldosterone release.


[The influence of dopamine on hemodynamics, microcirculation and renal function in patients with hypnotic drug intoxication (author's transl)].

The effect of dopamine on hemodynamics (CO, AoPm, TPR, SV, SW, CVP, PAPm, PAEDP), microcirculation (MBF, PS-product) and renal function (VU, CKI, CNa, CK, Cosm, TcH2O) was studied in 8 patients with hypnotic drug poisoning. With increasing doses of dopamine, cardiac output and heart rate increased and the peripheral resistance decreased. An augmentation of stroke volume and left ventricular stroke work was observed in the low dose range only (200--400 mug/min). With increasing doses, central venous pressure as well as mean pulmonary artery pressure and enddiastolic pulmonary artery pressure decreased. No vasoconstriction was found in muscle tissue vessels even with large doses of dopamine. This is explained by the vasoplegic properties of hypnotic drugs. In circulatory shock associated with hypnotic drug poisoning, dopamine develops only minor pressure effects in contrast to its action in circulatory shock of cardiogenic or septic shock origin. High doses of dopamine result in a significant increase in heart rate, without concomitant increase in stroke volume and blood pressure. Therefore the dosage of dopamine should not exceed 400 mug/min in these cases. A combination with small doses of norepinephrine (10--20 mug/min) seems to be more effective. Renal function tests showed variable expansion of urine volume, glomerular filtration rate, and clearances of sodium, potassium and osmotic substances. Therapy with dopamine might increase the renal elimination rate of hypnotic drugs.


A comparison of catecholamine concentrations and dopamine-beta-hydroxylase activities in plasma from normotensive subjects and from patients with essential hypertension at rest and during exercise.

In 8 normotensive subjects and in 8 patients with essential hypertension total catecholamine content and dopamine-beta-hydroxylase (DBH) activity in plasma were measured at rest and during physical exercise. Catecholamine levels at rest were significantly higher in the hypertensive than in the normotensive persons whereas the 2 groups of subjects did not differ in DBH activity at rest. At a work load of 150 watts there was a more pronounced increase of the catecholamine concentrations and of the DBH activity in the hypertensive patients than in the normotensives. One may conclude from the data that there is an increased sympathetic nerve activity in patients with essential hypertension.


[Histocompatibility-(HLA) antigens in patients with HBsAg positive and negative hepatitis and healthy carriers of HBsAg and anti-HBs. (author's transl)].

New own data and a survey of published data concerning the frequencies of 23 HLA antigens in patients with HBsAg positive and negative chronic active hepatitis (CAH) and healthy carriers of Hepatitis-surface antigen (HBsAg) and high titers of antibodies to HBaAg (Anti-HBs) allow to conclude as follows: 1. Patients with CAH and persistence of HBsAg show a normal frequency of HLA-B8. 2. There is no increased frequency of HLA-B8 in HBsAg negative CAH without autoimmune antibodies. 3. Only in patients with HBsAg negative CAH with autoimmune antibodies is the frequency of HLA-B8 is statistically significantly increased (p less than 0.01 after correction for the number of antigens and different groups of patients compared). These are patients with the autoimmune form of CAH. 4. There exist no significant differences in the frequencies of the HLA antigens tested in patients with HBsAg positive CAH and healthy carriers of HBsAg and Anti-HBs. Thus no indications could be found for HLA-associated factors in the different behaviour to the hepatitis-B virus.


[Plasma glycosphingolipids: concentration and distribution in different types of hyperlipoproteinemia (author's transl)].

There are mainly four neutral glycosphingolipids in human blood plasma: Monohexosyl, dihexosyl, trihexosyl and tetrahexosyl ceramide. In patients with hyperlipoproteinemia (hlp) type IIa (n = 10), type IIb (n = 9), type IV (n = 24), and type V (n = 11) all four fractions of plasma glycosphingolipids were elevated compared to healthy subjects (n = 23). In all types of hlp monohexosyl ceramides were significantly augmented (p less than 1%). Trihexosyl and tetrahexosyl ceramides demonstrated only in single types statistically striking elevation. There was no significant elevation of dihexosyl ceramides. In the VLDL the distribution of all glycosphingolipids showed increase in hlp type IV and type IIb. In the LDL the distribution showed increase in type IIa. There exists a strong correlation with the elevated prae-beta-lipoproteins respectively beta-lipoproteins. It is concluded that elevation of glycosphingolipid levels in plasma is a metabolic consequence of hyperlipoproteinemia. It is considered that a part of plasma glycosphingolipids is de novo synthesized by the liver like VLDL. The role of plasma glycosphingolipids in atherogenesis is discussed.


[Humoral immune reactions on the hepatocellular plasma membrane in the experimental chronic active hepatitis in rabbits (author's transl)].

For the induction of experimental chronic active hepatitis (CAH) in rabbits long term immunization was performed with human liver-specific protein plus complete Freunds adjuvants. Serum antibodies against allogeneic hepatocellular membrane antigens could be detected after 23 weeks using isolated normal rabbit hepatocytes or by the passive hemagglutination technique with liver-specific membrane protein as antigen. Isolated hepatocytes from these rabbits showed in vivo fixed IgG on their plasma membranes in a linear and granular fluorescence pattern. Furthermore immune complexes (Raji-cell test) were detectable in the sera of these animals. After 23 weeks 3 out of 16 animals had developed a chronic active hepatitis (CAH). After 44 weeks 10 of 15 animals and after 78 weeks 6 of 7 surviving animals had a CAH. All these 7 animals had serum antibodies against membrane antigens of isolated rabbit hepatocytes and in vivo fixed IgG on their hepatocellular plasma membranes. The results suggest the existence of autoantibodies against hepatocellular membrane antigens. In addition, immune complexes may be bound to the plasma membranes. The pathogenetic role of these humoral immune reactions has yet to be determined.


Control of mineralocorticoid substitution in Addison's disease by plasma renin measurement.

In 7 out-patients with Addison's disease, plasma renin activity (PRA), plasma concentrations of angiotensin II (AT II), renin substrate (PRS), potassium, sodium and total protein, hematocrit, blood pressure, heart rate and body weight were studied after 2 weeks each on 2 mg of dexamethasone, 25 mg hydrocortisone (HC), 25 mg HC + 0.05 mg 9-alpha-fluorohydrocortisone (FC), 25 mg HC + 0.1 mg FC and 25 mg HC + 0.2 MG FC. Four further patients were less extensively studied. Mean PRA (upper normal limit, ambulatory: 12 ng AT I-ml-1-h-1) after the 5 steps of incremental substitution, starting with dexamethasone, was 192, 59, 38, 24 and 9 ng AT I-ml-1-h-1 rsp. PRS did not change with increasing substitution. PRA and AT II were significantly correlated (r = 0.91; p less than 0.0001) and proved to be the most sensitive parameters of insufficient mineralocorticoid substitution. With decreasing significance, PRA also correlated with plasma protein concentration, plasma sodium concentration (negative), delta body weight (negative), heart rate, delta mean blood pressure (negative) and plasma potassium concentration. PRA or AT II measurements are useful clinical tools to control mineralocorticoid substitution in Addisonian patients. Inappropriately high substitution can be prevented by keeping PRA in the upper normal range.


[Failure of platelet spreading in thrombasthenia due to changes of high molecular weight membrane glycopeptides (author's transl)].

Rabbit and thrombastheinic platelet membranes were examined by SDS polyacrylamide gel electrophoresis. Both rabbit and thrombasthenic platelets failed to spread on siliconized glass surfaces and revealed platelet membrane glycoprotein patterns quite different from those of normal human platelet membranes. Typical for normal platelet membranes are four high molecular weight glycoprotein bands. The platelet membranes from rabbits and from one thrombasthenic patient showed only the first major glycopolypeptide with an apparent molecular weight of 135000 and 120000 D respectively. Other platelet membrane glycopeptides (both the carbohydrate and polypeptide moiety) were completely absent in thrombasthenia. The rabbit platelet membrane yet contains two strong polypeptides in this high molecular weight region, however, without corresponding carbohydrate moieties. Therefore, we support the view that the carbohydrate chains from two high molecular weight glycoproteins are of importance for platelet spreading on glass surfaces.


[Migration inhibition of mononuclear cells in idiopathic adrenal insufficiency. Inhibition of migration of mononuclear cells with adrenal microsomes and blocking of the reaction by adrenal antibodies (author's transl)].

In 19 patients with idiopathic adrenal insufficiency and in 19 controls, cellular (as measured by the migration inhibition test) and humoral (by means of immunoflourescence) immune reaction to adrenal antigens were investigated. Significant inhibition of migration was observed in 12 patients with adrenal microsomes; migration of mononuclear cells was however within normal range in 18 out of 19 controls. Adrenal antibodies could be detected in 11 (53%) of the patients. In a further series of investigations adrenal microsomes have been preincubated with specific antibody and used in migration inhibition tests. The migration indices observed with microsomes were compared to those obtained with microsomes preincubated with adrenal antibody. Migration inhibition with microsomes could be blocked by antibody in almost all antibody-positive patients. No uniform trend on the migration of mononuclear cells was found in the antibody-negative patients. A blocking of the cellular immune reaction by specific antibody seems likely. Possible mechanisms which could lead to such phenomena as well as the biologic significance of adrenal antibodies are discussed.


[Immunoreactive parathyroid hormone, 25-hydroxycalciferol and bone histology in renal osteodystrophy (author's transl)].

Immunoreactive parathyroid hormone (iPTH) and 25-hydroxycalciferol (25(OH)D) serum levels were determined in 32 patients with renal osteopathy, they were correlated with the results of bone biopsy and other clinical parameters. iPTH was closely related to bone histology, it did not correspond to serum calcium and alkaline phosphatase, but the correlation to serum phosphate was statistically significant. 25(OH)D levels were not related to the histological findings of osteomalacia or increased bone resorption, while a correlation between the vitamin D metabolite and serum calcium could be observed. Since iPTH and 25(OH)D levels exhibited a significant correlation, an inhibitory effect of 25(OH)D on parathyroid gland function in renal failure was discussed.


[Oral glucose tolerance test with a mixture of oligosaccharides after partial gastrectomy (author's transl)].

Fourteen non-diabetic male patients undergoing partial gastrectomy for ulcer disease were investigated with oral glucose tolerance test using a 100 g mixture of oligosaccharides. Partial gastrectomy had been performed between 1 and 3 years ago. Compared to seven healthy male control subjects, patients had significant higher blood glucose levels at 30 and 60 min and a more rapid descent, so that at 120 and 180 min no differences were found between patients and control subjects. With the usual criteria (blood glucose levels at 120 and 180 min) the non-diabetic patients with partial gastrectomy showed normal test results.


Permanent outdoor housing for woodchucks, Marmota monax.

Permanent outdoor housing for woodchucks (Marmota monax) was constructed from chain link fencing sections on a concrete base. Metal poultry nest boxes were attached to 1 side of the cage. Each enclosure accommodated up to 10 woodchucks and provided adequate shelter and exercise space. This housing system was inexpensive to construct and efficient to service.


Mycoplasma pulmonis infection in gnotobiotic and conventional mice: aspects of pathogenicity including microbial enumeration and studies of tracheal involvement.

Intranasal inoculation of Mycoplasma pulmonis into gnotobiotic mice resulted in positive cultures from the anterior nares, nasopharynx, trachea, and lungs persisting for 21 da. Similar inoculation of conventional, mycoplasma-free mice resulted in an increase in colony-forming units reaching a maximum by the 8th post-inoculation day and remaining constant in trachea and lungs through the 22nd day by an organ homogenate serial dilution method. All mice appeared ill with loss of total body weight, an increase in lung weight, and a peak of mortality between the 6th and 8th days. Between the 8th and 22nd, day, the number of deaths declined and survivors improved in appearance despite persistence of large numbers of colony-forming units in the trachea and lungs. M pulmonis was demonstrated in the trachea by immunofluorescence and electron microscopy.


Influence of age on thyroidal 131I uptake in Beagle pups.

Parameters in radioiodine metabolism by the thyroid gland were investigated in 98 beagle pups 0-110 da of age and in 6 adults. Significant age-related differences in thyroidal 131I uptake, uptake/g of thyroid, and retention and subsequent radiation dose were observed. Significant differences were also found in uptake/g, retention and subsequent radiation dose were observed. Significant differences were also found in uptake/g, retention, and dose between litters of the same age. Seventy-da-old pups had the highest mean uptake (approximately 25% of the administered dose) and fastest release rate (effective half-life approximately 3.6 da), whereas neonates less than 12 hr of age showed the highest peak concentration (157% of administered dose/g thyroid). The calculated radiation doses to the thyroid were highest in newborn pups, averaging over 100 rads per microcurie of 131I administered, or about 10 times the dose/muCi for adults.


Some hematologic and temperature determinations in the 7-banded armadillo (Dasypus hybridus).

Hematologic values were determined for 10 male and 16 female 7-banded armadillos (Dasypus hybridus), known as the "mulita" in Argentina. Values for females and males, respectively, were: PCV 40.47 +/- 1.26 and 39.67 +/- 1.40 ml/dl; sedimentation rate 15.3 +/- 3.26 and 10.6 +/- mm/hr; RBC 6.001 +/- 0.128 and 5.963 +/- 0.170 X 10(6)/mm3; WBC 8.425 +/- 1.417 and 10.084 +/- 1.001 X 10(3)/mm3; hemoglobin 16.14 +/- 0.66 and 16.84 +/- 0.52; MCV, MCH, MCHC, and differential leukocyte count were also determined. An ultrastructural study of neutrophilic leukocytes and sex chromatin was made. Rectal temperatures ranged from 29.5-32 degrees C. These results were compared with findings for the 9-banded armadillo (Dasypus novemcinctus).


Two operative technics applied in perinatal research in the rhesus monkey.

Methods for percutaneous transabdominal amniocentesis and umbilical artery cannulation as modified and applied to the perinatal study of the rhesus monkey were described. These technics proved to be reliable, reproducible, and safe when used with care and attention to sterile technic.


A compact, versatile inhalation exposure chamber for small animal studies.

An inhalation exposure chamber was designed to fit conveniently into a standard laboratory exhaust hood. The chamber was constructed entirely of non-corrosive materials and was suitable for continuous exposure of 6 small laboratory animals to corrosive atmospheres such as ozone. A separate, outer chamber surrounding a smaller, inner chamber permitted access to each individually housed animal without disturbing the experimental atmosphere. Facilities were available for ad libitum access to food and water for chronic exposures. The chamber was easily disassembled for cleaning. A safety mechanism was described which automatically stops the generation of a toxic gas in the event of an exhaust system failure.


Mortality in red-sided garter snakes, Thamnophis sirtalis parietalis, due to larval nematode, Eustrongylides sp.

Garter snakes, Thamnophis sirtalis parietalis, that had been fed wild-caught banded killifish, Fundulus diaphanus, and laboratory-bred leopard frogs, Rana pipiens, were infected by larval nematode, Eustrongylides sp; 7 of the 25 snakes died. Signs of infection in 20 snakes included subcutaneous "lumps," violent contortions, and bloody exudate, apparently from the nares. Nemotodes were collected at necropsy from beneath the skin, in the lungs, in the body cavity, and along the spinal column. Nematodes were surgically removed from subcutaneous sites in 2 garter snakes, which recovered completely.


A rapid testing procedure to determine low levels of ocular irritation.

A new and rapid method for testing low levels of ocular irritation using a balanced incomplete block design, a new grading system, and statistical analysis of the results, has been developed. Two drops (0.1 ml) of 1 of 5 ophthalmic solutions were instilled into the conjunctival sac of the right or left eye of each of 10 New Zealand white [Deb:(NZW)] rabbits hourly for 9 hr on 4 consecutive da. Before the study and before the first instillation on each day, the eyes were examined with a direct ophthalmoscope, and the reactions were graded according to a modification of the system in the illustrated Guide for Grading Eye Irritation by Hazardous Substances. The new procedure showed that 1 of the 5 solutions elicited a significantly more severe (p less than or equal to 0.05) ocular response of redness, chemosis, and discharge than did any of the other 4 solutions. Previous testing of this solution in rabbits by standard laboratory procedures and the Draize method of grading ocular irritation failed to detect these reactions.


Isolation of an atypical Pasteurella-like organism from guinea pig abscesses.

Four of a group of 33 (12%) guinea pigs were found to have subdermal abscesses. Bacteriologic culture produced an aerogenic Pasteurella-like organism. There is some indication that the Gram-negative rod may be a yet unclassified pathogen with a predilection for guinea pigs.


Variations in the relationship of the major vessels of the left coronary groove in the dog.

The anatomic relationship of the 2 major vessels of the left coronary groove was studied in 140 dogs. Five basic patterns of disposition were observed: 1) circumflex artery superficial from its origin to the caudodorsal cardiac margin, coronary vein deep and not visible (22%); 2) coronary vein superficial from the ventral interventricular septum to the caudodorsal cardiac margin, circumflex artery deep and not visible (15%); 3) circumflex artery and coronary vein both superficial and running parallel with each other along the groove (8%); 4) coronary vein crossing circumflex artery at some point along the groove (44%); and 5) circumflex artery crossing coronary vein at some point along the groove (11%). These variations were found to influence certain experimental modifications of the left circumflex blood flow in the dog.


Evaluation of fecal technics for the diagnosis of cat liver fluke infection.

The comparative efficiency of 5 standard technics for the detection of feline liver fluke ova in feces was evaluated. The formalin-ether technic proved superior to direct smear, sugar flotation, zinc sulfate flotation, or detergent sedimentation technics. The formalin-ether technic correctly diagnosed all Platynosomum concinnum-infected cats studied, as confirmed by necropsy findings.


A survey of aquarium fishes, their foods, and environmental water for salmonellae.

The presence of salmonellae in the pet shop environment, fishes, aquarium water, and in a variety of commercially prepared and natural fish foods was determined. Salmonellosis attributed to turtles purchased from pet shops has been responsible for an estimated 280,000 human cases annually in the United States. The possibility that aquarium fishes, or their food and aquatic habitat might also serve as sources of human salmonellosis was deemed worthy of clarification. Results of the present survey indicate that this is probably not correct, and a public health hazarddoes not exist.


Electrophoretic analysis of normal Beagle dog serum for changes possibly due to age or sex.

Serum protein, glycoprotein, and haptoglobin values were presented from normal male and female beagle dogs, 0.64 10.60 yr of age. The data presented as means +/- 2 standard deviations and coefficients of variation are important in evaluating clinical changes in experimental beagles.


Plasma progesterone level in the female armadillo during delayed implantation and gestation: preliminary report.

Ovulation in the armadillo was followed by an increase in the plasma level of progesterone to 10 ng/ml. The plasma concentration of progesterone decreased to approximatley 5 ng/ml during the 3 1/2 mo of delayed implantation and then increased to approximately 20 ng/ml for the 4 1/2 mo period of gestation.


Proliferation of renal interstitial cells following injury induced by ureteral obstruction.

The proliferation of renal interstitial cells was studied by the use of tritiated thymidine incorporation following unilateral ureteral obstruction in the rabbit. There was a nonuniform response with significant increase in nuclear labeling in the obstructed kidney in all zones at 24, 48, and 72 hours following obstruction with the exception of the inner medulla where the counts at 24 and 48 hours were not significantly different from sham-operated controls. The major labeling occurred in interstitial fibroblasts. Within the zones of high labeling (cortex and outer medulla) these cells were separated by widening of the intersittial space. In the zone of low labeling (inner medulla) the interstitial cells maintained their normal spatial relationships.


Segmental mediolytic arteritis: a clinical pathologic study.

A distinct arterial lesion was observed in the large abdominal muscular arteries in three autopsied patients. The salient histopathologic feature of this arterial lesion was either partial or total mediolysis. This was accompanied by a linear fibrin deposit between the media and adventitia and a variable nonpleomorphic inflammatory infiltrate. Total mediolysis led to the formation of arterial gaps. Disecting aneurysms frequently occurred and began either adjacent to arterial gaps or as a result of capillary hemorrhages in areas of partial mediolysis. Ruptured aneurysms led to massive intraabdominal hemorrhages. Arterial luminal occlusion, either by thrombi or dissection, resulted in ischemic bowel changes and renal infarcts. In addition, the arteries affected by mediolysis also showed medial degenerative changes, akin to cystic medial necrosis. Concomitant changes in the kidney showed mesangial hyperplasia; the heart exhibited histiocytic infiltrates and rare Aschoff-like bodies and capsular inflammation were seen in the spleen. The pathogenesis of the arterial lesions is unknown. A possible explanation is that this arteritis may have been induced by immune complexes and that local arterial medial degenerative changes predispose the involved arteries to immunologic injury.


Hypercalcemic VX-2 carcinoma in rabbits: a clinicopathologic study.

Rabbits receiving intramuscular injections of VX-2 carcinoma cells in biceps femoris muscles developed rapidly progressive neoplastic growths at 14 to 21 days associated with a significant hypercalcemia. The biologic behavior of the VX-2 carcinoma was characterized by local infiltration and metastases to regional lymph nodes and lungs. No metastases to skeletal tissues were evident. Femora from intramuscularly injected rabbits had varying degrees of osteophytosis and lysis evident roentgenographically. Histopathologic evaluation of femoral sections revealed periosteal new bone growth, cortical osteolysis, endosteal new bone growth, and in a few long term rabbits, pathologic fractures. Bone lesions were evident histologically in the vicinity of neoplastic growth (i.e., femora, tibiae) but not at distant sites (i.e., humeri and vertebrae). Mineral analyses of VX-2 carcinoma tissues and kidneys from VX-2-bearing rabbits revealed concentrations of calcium 83 and 3 times greater, respectively, than those of skeletal muscle and kidneys from controls. These findings correlated well with histochemical evidence of excessive amounts of calcium in sections of kidneys and VX-2 carcinoma tissues. Rabbits receiving intraperitoneal injections of VX-2 carcinoma cells did not develop hypercalcemia despite an extensive, progressive neoplastic burden with metastases to abdominal and thoracic viscera. Roentgenographic, histopathologic, and physiochemical analyses of selected bones from these rabbits revealed no significant alterations. These findings indicate that VX-2 carcinoma cells need to be in close proximity to skeletal tissues in order to induce hypercalcemia. The development of a significant hypercalcemia in intramuscularly injected rabbits precedes the invasion of osseous tissues by VX-2 carcinoma cells. Therefore, it appears that VX-2 carcinoma cells have the ability to alter skeletal morphology and physiochemistry through a dual humoral/cellular mechanism. The clinicopathologic characteristics of the VX-2 carcinoma in the rabbit suggest that the neoplasm is a good experimental model to study osseous-mediated hypercalcemia of malignancy.


Absence of enhanced intimal thickening in the response of the carotid arterial wall to endothelial injury in hypercholesterolemic rats.

Young male Sprague-Dawley rats fed a high cholesterol, thyroid-suppressive diet were subjected to drying injury of carotid artery endothelium; animals were sacrificed at various times up to 3 months after injury, and the vessels were examined by light, scanning, and transmission electron microscopy. The diet induced marked elevation of serum cholesterol mainly present in lipoproteins of density less than 1.063. The morphology and degree of intimal thickening in the injured carotids of such animals were compared with the changes found in control groups of normolipemic rats. In the control groups, endothelium was completely regenerated between 7 and 14 days; intimal thickening was present at 14 days and at later stages and contained smooth muscle cells without lipid. In the cholesterol-fed animals, endothelial regeneration and intimal thickening occurred as in the controls with the following additional features: in the zone of intimal thickening in the injured segment, lipid was present in smooth muscle cells and, at later stages, in the extracellular matrix; undifferentiated mononuclear cells were also noted in the thickened intima and, at 3 months, were found adhering to normal and regenerated endothelium. However, no differences were found between control and hypercholesterolemic rats with respect to the degree of intimal thickening within the injured segment; enhancement of the smooth muscle proliferative response was not evident in the hypercholesterolemic rats. Our findings suggest that this form of hypercholesterolemia and its associated hyperlipoproteinemia may not be directly responsible for rat smooth muscle proliferation following endothelial denudation. They also indicate that hyperlipemia does not necessarily cause persistence of myointimal hyperplasia in arteries.


Plasma membrane changes in freeze-fractured rat kidney cortex following renal ischemia.

Ischemia was produced in the inner cortex of the rat kidney by clamping the pedicle (artery, vein, and ureter) and severing collateral connections. After 30 minutes of ischemia, a slight aggregation of membrane-associated particles was observed in the freeze-fractured plasma membranes. The aggregation was progressive after 60 and 120 minutes of ischemia. These changes were reversible after 15 and 240 minutes of reflow of blood following 30 or 60 minutes of ischemia. The changes were irreversible after 120 minutes of ischemia. The cells were vacuolated after ischemic periods of 30 minutes or longer and after 120 minutes of ischemia the tissue was severely damaged and aggregation of membrane-associated particles was evident in the vacuolar membranes. No changes in the tissue or plasma membrane were observed after 5 or 20 minutes of ischemia.


Renal carcinomas and erythrocytosis in rats following intrarenal injection of nickel subsulfide.

In rats, an intrarenal injection of nickel subsulfide (Ni3S2) regularly caused, within 2 months, an erythrocytosis and eventually a renal carcinoma in 40 per cent of the animals. Despite their great pleomorphism, the neoplastic renal cells appeared to be of the same lineage but showed a pronounced tendency to evolve toward an anaplastic, spindle-cell variant. By electron microscopy, they exhibited varying degrees of differentiation with surface specialization, suggesting an epithelial origin. There was no indication that the erythrogenic and carcinogenic responses to Ni3S2 were interrelated as the high hemoglobin and erythrocyte values tended to retrocede with the development of the renal carcinoma. Other nickel salts and a variety of divalent metallic preparations failed to produce similar changes when administered under identical conditions. The possible mechanism of NI3S2 at the cellular level is briefly discussed.


The epithelial and capillary basal laminae of the placenta in maternal diabetes mellitus.

The thickness of the epithelial and endothelial basal laminae was determined in placentas from mothers without known metabolic disease (control) and mothers with diabetes mellitus. The measurements were carried out on electron micrographs. Frequency distributions and statistical parameters were calculated; in 20 cases, 16,331 values were measured. In all cases, the epithelial and endothelial basal laminae were thickest in edematous and fibrotic villi. They were thinner in placentas from diabetic mothers than in controls. Particularly thin basal laminae were found in regions with syncytiovascular membrances. The thinner basal laminae found in the placentas of diabetic mothers are considered to be the result of compensatory growth processes with formation of ontogenetically younger villous parts. The thicker basal laminae in fibrotic and edematous villi may result from a swelling of the basal laminae or possibly from an increased synthesis or a decreased decomposition of the basal laminae. The finding of very thin basal laminae in the region of the so-called syncytiovascular membranes may be of importance for the placental exchange function.


Comparison of human polycystic and medullary cystic kidney disease with diphenylamine-induced cystic disease.

Because of difficulty in obtaining cystic human kidneys for functional and morphologic study, animal models are receiving increasing attention. Most prominent among them is the renal cystic disease that is induced in rats through feeding of the antioxidant, diphenylamine, The present study examined the morphology of adult polycystic and medullary cystic kidney disease in man using scanning electron microscopy and compared them with diphenylamine-induced cystic kidney disease in rats. Diphenylamine nephropathy was induced by feeding rats 1 per cent diphenylamine for 12 to 18 months. All types of cystic disease showed changes in the renal corpuscles, including dilation of Bowman's space, podocyte fusion and degeneration, and basement membrane thickening. Cysts were noted along the entire nephron in polycystic and diphenylamine-induced cystic disease but only along the collecting ducts in medullary cystic disease. Cysts in polycystic disease were large and lined by flattened epithelium. Collecting duct cysts in diphenylamine cystic disease were lined by cells of irregular size and shape suggestive of cell hypertrophy and/or hyperplasia, whereas cysts of medullary cystic disease were lined by flattened epithelium except where the nephron entered or left the cyst. Cast material was generally found in the cysts of diphenylamine-induced and polycystic kidney disease but not medullary cystic disease. Atrophic glomeruli and tubules were found in all three diseases. Complete tubular obstruction was found in none; however, larger cysts frequently impinged on adjacent tubules and narrowed their lumina. The results of this study show that, in the terminal stages, cellular as well as gross morphologic differences exist between polycystic and medullary cystic kidney disease and that diphenylamine-induced cystic disease more closely resembles human polycystic than medullary cystic kidney disease.


Monte Carlo calculation on trans/cis-polysarcosine.

Monte Carolo calculations were made on unperturbed trans-polysarcosine chain, non-self-intersecting trans-polysarcosine chain, and also non-self-intersecting trans/cis-polysarcosine chain by using a hard-sphere model. In the last case, an attempt was first made to introduce cis amide bond into the Monte Carlo calculation of polypeptide chain. Dipeptide energy maps for four different trans/cis dyad sequences were calculated. The allowed regions were consistent with the pairs of dihedral angles observed in cyclo-pentasarcosyl and cyclo-octasarcosyl. The mean-square end-to-end distance and higher even moments were obtained. The distribution function of the end-to-end distance was calculated from the even moments by using Nagai's equation and compared with the direct Monte Carlo data. The best agreement was obtained by cutting off the terms containing much higher order even moments than a critical order. The fractions of cis amide bond and of the four different trans/cis dyad sequences in polysarcosine were calculated. The results of calculation were compared with the 220-MHz NMR spectra of polysarcosine in three different solvents. Qualitative agreement was stained for longer chains.


Geometrical criteria for formation of coiled-coil structures of polypeptide chains.

Crick's general formulas describing a coiled coil are expressed in a different form to combine the parameters of a coiled coil with the backbone dihedral angles of a polypeptide chain, assuming that the bond lengths and bond angles of the chain are fixed. While the existence of a low-energy coiled-coil conformation depends on energetic considerations, these formulas, which pertain to single-stranded structures and, by application of symmetry operations, to multistranded structures, provide the geometrical criteria for the existence of coiled coils. The concept of "the averaged structure of the minor helix", introduced here, makes it possible to relate the shape of the major helix to that of the minor helix. It is shown, in the analysis of a simple model of a single-stranded coiled-coil beta structure, that strong geometrical restrictions exist for the formation of coiled-coil structures from a given minor helix conformation of a polypeptide chain; these restrictions are expressed in a general form that is applicable to any coiled-coil of any number of residues in a repeat unit. As an application, the possible existence of a two-stranded coiled-coil antiparallel beta structure is considered, both geometrically and energetically, and discussed in relation to the observed twisted beta structures in globular proteins. The proposed coiled-coil models of alpha-helical proteins are also examined briefly.


On the oxy analogues to the 3 leads to 1 intramolecularly hydrogen-bonded peptide conformations.

The possible occurrence of the oxy analogues to the 3 leads to 1 intramolecularly hydrogen-bonded peptide conformations (main feature of the gamma turn), recently proposed in solution by several authors, has been investigated in a number of N-tert-butyloxycarbonyl-alpha-amino acids by x-ray diffraction, infrared absorption, proton magnetic resonance, and circular dichroism techniques. These folded conformations are absent in the solid state in all cases so far examined; however, they seem to be present in solution, the extent of the population of these forms in the conformational equilibrium mixtures being solvent, temperature, and structure dependent. In the solid state N-tert-butyloxycarbonyl-D-valine has the urethane-CONH-group in the cis configuration; this is the first time such a configuration has been found in the solid-state for a secondary amide group in a linear compound.


Stability of cis, trans, and nonplanar peptide groups.

Conformational energy calculations using ECEPP (Empirical Conformational Energy Program for Peptides) were performed on the molecular fragment Calpha1C'ONHCalpha2, on N-methylacetamide, and on several peptide molecules including N-acetyl-N'-methylglycineamide (Gly single residue), N-acetyl-N',N'-dimethylglycine-amide, and N-acetyl-N'-methylamide dipeptides of Gly-Gly and Gly-Pro. Energy minimization was carried out with peptide groups taken in both the cis and trans conformations, and the librational entropy and conformational free energy were determined at each minimum. It was found that the instability of cis in Gly-Gly comes primarily from interactions of the Calpha1 and HCalpha1 atoms with the Calpha2 and HCalpha2 atoms, and also from avorable interactions present in the trans form which are disallowed in the cis form, and from conformational entropy. The instability of cis in Gly-Pro is much less than in Gly-Gly because unfavorable interactions of the type CalphaH-CalphaH present in the cis conformation of Gly-Gly are present in both the cis and trans forms of Gly-Pro. The instability of cis in Gly-Pro arises mainly from the change in electrostatic energy caused by the restricted rotation about the N-Calpha bond of Pro. Entropy accounts for about 0.5 kcal/mol of the instability of cis in Gly-Pro compared with about 1.5 kcal/mol in Gly-Gly. The calculated fraction (4%) of cis in Gly-pro is in good agreement with the experimental value (5%) for related peptides in nonpolar solvents. When the dihedral angle omega of the central peptide bond in these dipeptides is allowed to vary during energy minimization, the deviations from planarity are only 1-3 degrees in low-energy minima of Gly-Gly but as much as 10 degrees in Gly-Pro. A comparison of these results with calculations in which the peptide bond was held fixed in the planar trans conformation shows that conformation-dependent properties of blocked dipeptides can be represented adequately without allowing omega to vary.


Competition between diftalone and other drugs for the binding site(s) on human serum albumin.

The influence of a series of drugs on the binding of diftalone to human serum albumin was investigated by equilibrium dialysis. The results indicated that among the different drugs tested phenylbutazone, indomethacin, warfarin and tolbutamide were, in the order listed, the most effective in displacing diftalone from its binding site(s). Additional investigation showed that there was no consistent inhibition by diftalone of warfarin and tolbutamide binding to albumin. The information obtained might prove useful in clinical therapy whenever a combination of drugs is to be administered.


On the oxy analogues to the 4 leads to 1 intramolecularly hydrogen-bonded peptide conformations.

The occurrence of the oxy analogue to the type II' 4 leads to 1 intramolecularly hydrogen-bonded nonhelical peptide conformation, recently proposed for t-BOC-Gly-L-Pro-OH in the solid state by Deber on the basis of infrared absorption evidence, has been disproved by x-ray diffraction analysis. This type of folding is also absent in solvents of moderate or high polarity. The latter conclusion is in agreement with Deber's results. However, in solvents of low polarity this intramolecularly hydrogen-bonded form could account for the strong negative Cotton effect near 230 nm observed in the circular dichroism spectrum.


Clinical follow-up and the cell-mediated cytotoxicity against HeLa cells in patients with invasive or preinvasive cervical cancer.

18% of patients with clinical stage Ib-IIa invasive cervical carcinoma, in contrast to 57% of patients with a more advanced carcinoma at the time of treatment, were positive in microcytotoxicity tests with peripheral blood lymphoid cells against HeLa cells in repeated tests 4--22 months after treatment. About half of the patients with cytotoxic lymphoid cells before treatment had lost this capacity at follow-up: the same was true of patients with severe dysplasia or carcinoma in situ. Eight out of 33 patients with mild epithelial dysplasia were cytotoxic at the start of the study. Five (62%) of the cytotoxic donors had signs of persisting epithelial atypia or of progressive disease, whereas only 7 (28%) of the 25 non-reactive patients had cytological abnormalities and in none had the disease progressed. Persisting cytoxicity at follow-up may thus be related to the continuing presence of the disease in these patients.


Amylose-iodine complex. I. Sedimentation behavior.

Sedimentation measurements are reported on solutions of blue amylose-iodine complexes in the range of 0.001 to 0.007% amylose. Amylose fractions B and F2, of weight average molecular weight average molecular weight 4.0 X 10(5) and 3.4 X 10(4), respectively, were used in this study. Iodine complexes of these fractions formed polydisperse solutions of limited solubility and stability. Sedimentation coefficients increased as a function of potassium iodide concentration. Values for fraction B complexes varied from (16.3 +/- 1.0) X 10(-13) at 1.2 X 10(-3) M KI to (57.2 +/- 7.5) X 10(-13) at 8.3 X 10(-3) M KI; values for fraction F2 complexes varied from (10.0 +/- 1.2) X 10(-13) at 1.2 X 10(-13) M KI to (24.8 +/- 3.9) X 10(-13) at 9.5 X 10(-3) M KI. At constant potassium iodide concentration, sedimentation coefficients, within our experimental error of 10 to 15% standard deviation, are independent of amylose concentration. Time dependence of sedimentation coefficient values was observed for solutions either saturated or unsaturated with respect to the iodine-binding capacity of amylose. For iodine-saturated complex solutions, sedimentation coefficients extrapolated to zero potassium iodide concentration were two to three times greater than for the parent amylose. Measurements are evaluated in terms of possible polyelectrolytic charge effects and aggregation. Under conditions used in these experiments, aggregation of amylose-iodide complexes appears to be the mechanism responsible for the large increase in sedimentation coefficients.


Amylose-iodine complex. II. Molecular weight estimates.

Ultracentrifugation measurements made by the Archibald method on solutions of amylose-iodine-iodide (AI) complexes, containing 0.003% amylose of weight average molecular weight 4.0 X 10(5) at 3.6 X 10(-3) M KI, yield an apparent molecular weight at the meniscus of 8 X 10(5) when measurements are extrapolated to 1200 rpm. Sedimentation equilibrium measurements at 1200 rpm yield apparent molecular weight at the meniscus of 6 X 10(5) and at the cell bottom of 2.4 X 10(6). Heterogeneity and aggreagation are major features of AI complex solution behavior. Apparent molecular weights increase as a function of increasing potassium iodide concentration and with time. This behavior directly correlates with AI complex sedimentation coefficient behavior previously reported. Molecular weight estimates are of the same order for AI complex solutions saturated and 65-70% saturated with respect to the iodine-binding capacity of amylose. Qualitative estimates of net macroion charge effects upon apparent molecular weights are presented.


Decreased proteolysis and increased amino acid efflux in aging human fibroblasts.

The release of radioactivity was measured following variable times of dual labeling of normal human fibroblasts at early and late passage and late-passage cell strains derived from the progeria and Werner's syndrome of premature aging. In the rapid first phase to 20 min, all 3 late-passage (aged) cells released more acid-soluble radioactivity into the medium than early-passage normal cells in the order Werner's greater than progeria greater than late-passage normal greater than early-passage normal, virtually all of this radioactivity emanating from intracellular material that was acid-soluble after prelabeling (zero time). In the slower second phase from 20 min to 3 h, all 4 cell types showed approximately parallel profiles of release. Following preloading with the non-utilizable amino acid alpha-amino[14C] isobutyric acid, progeria and Werner's cells released radioactivity more rapidly than did early- and late-passage normal cells in that order. In contrast, direct measurements on the net loss of counts from acid-insoluble material, i.e. true proteolysis, revealed that all 3 aged cells degraded proteins of short half-life more slowly but proteins of long half-life were degraded at the same rate as those of young normal cells. The results indicate that aged cells have a reduced proteolytic capacity and increased amino acid efflux. The latter process is probably due to the higher proportion of labeled amino acids in the cell water of aged cells at zero time and possibly increased membrane leakiness. The reason for the decreased proteolysis is not clear but it may relate to the rising proportion of defective proteins, the increased protein content and the loss of replicative capacity in aging cells.


Characterization of residual bodies fromed in phase II cultivated human glia cells.

Residual body-like structures have been shown to occur in small numbers in actively growing in vitro cultivated phase II human glia cells. In contact inhibited phase II glia cells they have been shown to accumulate. Whether such structures are analogous to lipofuscin pigment granules in post-mitotic cells in vivo has been uncertain. We have characterized such bodies in actively growing and contact inhibited cells as to their acid phosphatase content, heavy metal content, autofluorescent characteristics, staining characteristics and morphology. It has been shown that many of these bodies are acid phosphatase positive, contain heavy metals, show the natural and characteristic fluorescence of lipofuscin pigment, are PAS-positive, acid fast with Ziehl-Neelsen and are morphologically similar to lipofuscin. They are thus analogous to the lipofuscin granules found in post-mitotic cells in vivo. The number of such granules was found to increase following contact inhibition of the mitotic activity. We conclude that lipofuscin granules are found continuously in the culture and that the cellular content of these granules can be diluted by cell division.


Women and national health insurance: issues and solutions.

An effective national health insurance program should provide adequate, continuous, and comprehensive coverage for all. In framing current proposals, it seems that policy makers have not adequately considered differences in medical care utilization and needs between men and women. The inequities which result occur primarily because women now have two central sources of medical care--an obstetrician/gynecologist and a general practitioner or internist-while men have only one. The article delineates four issues of particular importance to women: 1) eligibility provisions which insure women through their husbands' policies; 2) benefit structures which exclude aspects of reproductive health services and/or fail to explicitly recognize women's two central sources of care; 3) provider certification provisions which exclude free-standing clinics and/or nonphysician personnel, and 4) incentives for reform of health delivery which force women to choose between their two current sources of care. The analysis concludes that current proposals contain provisions which, if enacted, would lead to inequities for women. Alternative solutions which might be explored are discussed and principles which could serve as guidelines for developing specific proposals are presented.


AUTOGRP: an interactive computer system for the analysis of health care data.

AUTOGRP is an interactive computer system designed to facilitate rapid analysis of complex medical information. AUTOGRP allows the clinical or administrative expertise of the user to be combined with sophisticated computer techniques to permit rapid information retrieval, hypothesis testing, development of norms, and identification of deviant cases. This interaction yields results of a uniquely high statistical and medical quality. AUTOGRP has been used to aid in understanding the process of patient care management in a variety of settings in order to enhance the effectiveness of decision-making from both a medical and management point of view.


Geographic access to hospital care: a 30-minute travel time standard.

A review of literature focusing upon geographic accessibility to health facilities indicates that while distance has been the traditional measure, travel time may now be a more meaningful indicator. Applying a 30-minute travel time standard to general hospitals, as advocated by various health plans, this paper illustrates an approach to the determination of geographic accessibility through a combination of a travel time file and sociodemographic profiles. Focusing upon all residents of West Virginia, the study identifies the number and characteristics of persons who reside within and beyond the 30-minute standard. More than 10 per cent of the entire population and nearly 20 per cent of the rural residents live in areas which are, by this standard, inaccessible to general hospitals. The "inaccessible" populations are characterized as having sociodemographic attributes associated with high medical needs. Other applications of travel time data are discussed.


Continuity and coordination in primary care: their achievement and utility.

Coordination is a hallmark of primary care. Efforts to improve primary care services should involve assessment of the extent to which coordination is achieved. Our study in three adult and three pediatric clinics demonstrates that existing information concerning patients' problems, therapies, tests, and referrals is often not recognized by primary care practitioners. Recognition of these types of information is better when the practitioner who provides follow-up care is the same from one visit to the next. Information about visits which were anticipated by the practitioner, and particularly the content of these visits, is often neglected. The largest deficit, however, is in recognition of both the occurrence and content of visits unanticipated by the primary care practitioner. Greater efforts to achieve better coordination of care, by improving either continuity of practitioner, communication among practitioners, or the information system, are required before this essential element of primary care becomes a reality.


Phenobarbital as a hypocholesterolemic agent in the rat and rabbit.

The administration of phenobarbital was observed to inhibit the rise in serum cholesterol that occurred in rats after thyroidectomy or hypophysectomy and in rabbits after inclusion of cholesterol in their diet. This hypocholesterolemic effect of phenobarbital was found to be due to its capacity to inhibit the intestinal absorption of cholesterol in both these species. We found no evidence to suggest that phenobarbital altered the endogenous process of cholesterol metabolism in either of these two species of animals.


Development of responsiveness of young normal rats to growth hormone.

Growth hormone (GH) exerts a biphasic effect on the membrane transport of amino acids and sugars in diaphragms from hypophysectomized rats. A stimulatory (insulin-like) effect of GH is observed for approximately 3 hr after the administration of the hormone, and then the diaphragm becomes "refractory" to further administration of the hormone for 24-48 hr. In the present study the in vitro responsiveness of diaphragms from young normal rats of different ages to bovine growth hormone (bGH) was studied by measuring the accumulation of alpha-aminoisobutyric acid (AIB), cycloleucine, and 3-0-methyl-glucose (3-OMG) and by determining the incorporation of phenylalanine into diaphragm proteins. bGH increased the uptake of AIB in 6, 10, 14, 18, and 22-day old and of cycloleucine in 10, 14, and 18-day old rats, respectively. The maximal stimulatory effect was seen in 18-day old rats and no effects were seen in 26 and 30-day old animals. A similar pattern of age-related responsiveness was also seen when the uptake of 3-OMG and the incorporation of phenylalanine were studied. The rate of accumulation of the nonutilizable amino acids, as well as the rate of incorporation of phenylalanine, decreased markedly with age. Fasting the rats for 20 hr did not change the principal age-related responsiveness of AIB transport to GH, but the magnitude of the hormone effect increased due to a lower uptake of AIB in control diaphragms. bGH had a dose-dependent effect on the accumulation of AIB in fasted 18-day old rats, the threshold concentration of bGH being 0.1 mug/ml. When diaphragms from 18-day old rats were incubated with bGH for various periods, the uptake of AIB was stimulated between 0 and 60 and 120 and 180 min, but not between 60 and 120 min after the start of the incubation. This observation indicated that the muscles were "refractory" to GH between 60 and 120 min. Preincubation of diaphragms from 21-day old rats with bGH for 3 hr did not inhibit the stimulatory effect of bGH added subsequently indicating that the duration of the "refractory phase" did not exceed 270 min in this group of rats. When diaphragms from fasted rats of different ages were preincubated in Krebs bicarbonate buffer for 3 hr, a stimulatory effect of bGH on AIB uptake was also observed in 26 and 30-day old rats, possibly because the influence of endogenous GH subsided during the preincubation period. These results suggest that diaphragms from "old" normal rats are insensitive to exogenous GH because the "refractory phases" become considerably prolonged with age.


Plasma glucagon after kidney exclusion: experiments in somatostatin-infused and in eviscerated dogs.

Bilateral kidney exclusion in the anesthetized dog is followed by a rapid and sustained increase in arterial plasma glucagon. This occurs even if endogenous glucagon secretion is inhibited by somatostatin or completely suppressed by abdominal evisceration and, in both cases, replaced by a constand infusion of exogenous glucagon. It is concluded that the rise in plasma glucagon occurring after bilateral kidney exclusion is not due to an increase in endogenous glucagon production but results from an abrupt cessation of kidney glucagon uptake.


Carbohydrate and lipid metabolism during human labor: free fatty acids, glucose, insulin, and lactic acid metabolism during normal and oxytocin-induced labor for postmaturity.

This investigation was performed to study the metabolism of the major body fuels (viz. glucose and free fatty acids), insulin, and lactic acid during the stress of human labor. In addition, the role of the normal placenta in the transport of these substances between mother and the fetus was evaluated by measuring them in the mother and cord blood at delivery. To study possible alterations of this role in the placenta which had exceeded the normal period of gestation, a second comparable group of women had labor induced with oxytocin 16-18 days beyond the expected date of delivery. A dramatic twofold increase in maternal plasma free fatty acids was observed during labor. There was a lesser but definite increase in blood glucose concentrations. No rise in serum insulin levels was noted which coincided with the changes in blood glucose. Lactic acid concentrations during the course of labor were variable from baseline but at delivery, the concentrations rose to very significant levels. Free fatty acids and blood glucose levels were significantly higher in the maternal than in the fetal side. A significantly positive correlation was noted between the maternal and cord blood values except for free fatty acids in the postmature group. No significant difference, nor a correlation was found between the two compartments in the insulin nor lactic acid levels. These results suggest that during human labor free fatty acids are the principal metabolic fuel. This increase in maternal free fatty acids may serve to spare glucose as a metabolic fuel in the fetus. The mechanism responsible for the increase maternal free fatty acid mobilization remains to be determined. It is not possible to discern any consistant alteration in placental function as a consequence of prolonged gestation.


Synthesis and degradation of methylated proteins of mouse organs: correlation with protein synthesis and degradation.

L-(Methyl-14C)-methionine was administered i.p. to mice, and the incorporation of radioactive methionine into proteins and methyllysine and methylarginine residues formed by the transfer of the methyl-14C group of methionine were measured. Tissue protein was actively methylated in organs having a high activity of protein synthesis, and the in vivo methylating activity in organs was not correlated with theprotein methylating activity of the organs determined in vitro. Puromycin inhibited both protein synthesis and protein methylation in mouse organs to a similar degree. Neither the formation of S-adenosyl-(methyl-14C)-methionine nor protein methylase was inhibited by puromycin. The data suggests that proteins are methylated immediately after protein synthesis, that is, newly synthesized proteins are the substrates of protein methylation. Radioactive methionine and the [C14] methyl groups of methyllysine and methylarginine residues of tissue proteins are degraded in parallel over a period of 3 wk, suggesting that protein methylation is an irreversible type of protein modification.


Reversible and irreversible glucose disposal in dogs: influence of fasting and cold exposure.

Rates of total glucose entry rate, irreversible loss, and recycling were measured in unanesthetized dogs with indwelling arterial and venous catheters. Four experimental conditions were selected: 16 or 26 hr of fasting and neutral (+25 degrees C) or cold (-21 degrees C) ambient temperatures. A mixture of U 14C-glucose and 2-3H-glucose was used as a tracer, according to the primed infusion technique. No matter what the ambient temperature was, increase of fasting time from 16 to 26 hr induced a slight, but nonsignificant, decrease in both the total glucose entry rate and the irreversible loss. At neutral ambient temperature, the amount of glucose promptly recycled was less after 16 hr than after 26 hr of fasting, while an opposite pattern was observed during cold exposure. Thus, that part of hepatic glucose entry promptly recycled was significantly increased from 22% (16 hr of fasting) to 31% (26 hr of fasting) at neutral ambient temperature. It remained almost unchanged (20% and 18%) in cold. It was, therefore, suggested that this increase might be considered as an compensatory mechanism, exerting a sparing effect on glucose utilization. This mechanism does not occur in cold ambient temperature, thus, worsening a possible shortage in glucose supply.


[The effect of metal ions on the lipolytic activity of Mycobacterium rubrum and Actinomyces streptomycini].

Hydrolysis of olive oil by intact cells of Mycobacterium rubrum 403 and "acetone" preparations of Actinomyces streptomycini 116 was found to be inhibited by the following ions: Ca2+, Mg2+, Mn2+, Ba2+, Co2+, Cd2+, Cu2+, Zn2+, Fe2+, Fe3+, Ni2+. Olive oil is hydrolyzed by the growing culture of Act. streptomycini 116 only in the presence of bivalent metal ions. The biosynthesis of lipase by Mycobatcerium rubrum 403 and Act. streptomycini 116 is increased twofold by magnesium ions. The biosynthesis of lipase by Act. stroptomycini 116 is stimulated also by calcium ions.


[An electron microscopic study of the vegetative mycelia of Actinomyces flavus during flavofungin biosynthesis].

The vegetative mycelium of a submerged culture of Actinomyces flavus 12 was studied by complex electron microscopy (negative and positive contrasting, cryofractography) in the course of biosynthesis of flavofungin. The antibiotic is accumulated first in the cytoplasm as singular small granules which later grow larger. Accumulation of flavofungin is accompanied with destruction of the cytoplasm, nucleoid and other structures. Secretion of the antibiotic is supposed to be accomplished according to holocrine type.


[Detection of cyanide resistant respiration among Candida lipolytics yeasts].

Conditions causing cyanide-resistant respiration were studied in the yeast Candida lipolytica. This type of respiration was found when the culture growing on glucose, glycerol, hexadecane, or acetate exhuasted the substrate and passed from the logarithmic to stationary growth phase; the same phenomenon can be induced by exhaustion of phosphorus or nitrogen in the glucose medium. The yeast culture growing on lactate, ethanol, pyruvate, alpha-ketoglutarate, malate, or succinate is characterized by cyanide-resistant respiration even at the beginning of the logarithmic growth phase. The values of pH in the incubation medium have no effect on the time of manifestation of cyanide-resistant respiration.


[Dark metabolism of Rhodospeudomonas sulfidophila].

A new strain of phototrophic purple bacterium Rhodopseudomonas sulfidophila RP-6 has been isolated from samples of the salty meromictic lake Repnoye. The bacterium utilizes thiosulphate yielding sulphates and assimilates molecular hydrogen in the darkness under aerobic conditions. Thiosulphate stimulates fixation of 14C-bicarbonate by the cells both in the light and darkness. Organic compounds are necessary for growth of the bacterium in the darkness. R. sulphidophila RP-6, R. palustus, and Rhodomicrobium vanniellii CO-1 do not grow in the presence of carbon monoxide neither in the light or in the darkness.