Surface properties related to concanavalin A-induced agglutination. A comparative study of several Entamoeba strains. Pathogenic strains of Entamoeba histolytica are more easily agglutinated with concanavalin A (Con A) than strains isolated from human asymptomatic carriers. All three pathogenic strains studied here were found to agglutinate with low concentrations of Con A in contrast to various nonpathogenic axenic strains of amebas, characterized by their ability to grow at room temperature. Our present observations suggest that the extreme susceptibility of pathogenic strains of E. histolytica to agglutinate with Con A is related to their higher capacity for lectin binding and to their lack of detectable repulsive charges at the cell surface. The amount of fluorescein-tagged Con A bound to the surface was much higher in pathogenic strains. Only nonpathogenic strains showed a detectable negative surface charge as studied both by means of cell microelectrophoresis and by labeling cells with cationized ferritin at 0 degrees C. The mobility of surface Con A receptors estimated as the percentage of caps was comparable in all strains. Results of one strain cultured in axenic and monoxenic conditions suggested that bacteria can modify the behaviour of E. histolytica trophozoites by altering surface properties of the amebas.


Generation of T-helper cells in vitro. II. Analysis of supernates derived from T-helper cell cultures. Supernates derived from in vitro generated T-helper cells have been analyzed for their capacity to substitute for T-cell carrier reactivity. T-helper cell supernates stimulate both a carrier-specific and nonspecific anti-DNP-PFC response to DNP-carrier conjugates in cultures of hapten-primed spleen cells. The carrier-specific and nonspecific activity can be distinguished by dosage optimum, antigen requirements, binding specificity for carrier, and in the requirement for additional splenic adherent accessory cell involvement. The active factors produced in this system are heat labile and sensitive to trypsin and periodate. They are removed by absorption with alloantisera directed toward the strain from which the supernate was derived but not by a variety of anti-immunoglobulin sera.


A rapid method, using octadecasilyl-silica, for the extraction of certain peptides from tissues. Peptides can be recovered from tissues by homogenization in a carefully selected extraction medium followed by adsorption from the supernatant on a small bed of octadecasilyl-silica. Recoveries of corticotropins and somatostatin added to a variety of tissues were quantitative, and the peptides undamaged as determined by high-pressure liquid chromatography.


Regeneration of the renal calyces after calycectomy: an experimental study. On 14 rabbits, 21 kidneys were subjected to a calycectomy or the tip of the papilla was cut off by caudal nephrotomy. During an observation period of 2, 4, 6, 8 and 10 days, and further after 3 and 6 weeks the macroscopic and microscopic investigations led to the following results clearly answering the question put at the beginning of the inquiry: (1) even if parts of the renal calyces are removed, a complete regeneration of the renal pelvic mucosa takes place in the damaged area; (2) regeneration of the mucosa begins in neighbouring renal pelvic epithelium and the epithelium of the collecting tubes; (3) regeneration starts on the 4th day and is essentially ended by the 3rd week; this regeneration extends over the whole of the injured area; after the 6th week the process is finished and no inflammatory changes are to be found in the damaged area, and (4) in the process of healing no fibrous tissue is formed at the occlusion of the lamina cribrosa in the area of the papilla; there is no demonstrable necrosis of the renal parenchyma where the mucosa was removed. Hydronephrosis in this area is evident, beginning on the 3rd or 4th day and is to be regarded as the result of inflammatory process or of the operation itself. It is partly in evidence after 6 weeks but is clearly in a regressive stage. Morphologically a functional loss of the affected area of renal tissue cannot be demonstrated. The four questions made and answered by this animal experiment allow the following conclusion: calycectomy can be successfully undertaken. Regeneration of the mucosa is almost finished after 3 weeks and finally completed after 6 weeks. Considerable cicatrisation in the area of the mucous membrane injury or of its nephrons is morphologically unimportant. Calycectomy should be preferred to polar resection as there is a smaller parenchymal loss.


Studies on the active principles of Schisandra sphenanthera Rehd. et Wils. The structures of schisantherin A, B, C, D, E, and the related compounds. Deoxyschisandrin (VIII) and five new lignans, named schisantherin A, B, C, D, and E, were isolated from the active fraction of the fruits of Schisandra sphenanthera Rehd. et Wils. Their configurations and conformations were established by exhaustive spectral analysis as well as chemical degradations as shown in Ia, Ib; IIa, IIb; IIIa, IIIb; IVa, IVb, and Va, Vb respectively, and their absolute configurations at biphenyl, at C6, C7, and C8 were all assigned to be S form. The position of the methylenedioxyl group in the structures of gamma-schisandrin and Wuweizisu C (as described in the literature), isolated from Schisandra chinensis, must be corrected as shown in VI and VII respectively. In pharmacologica studies and preliminary clinical trials, schisantherin A, B, C, and D showed good effect in lowering the serum glutamic-pyruvic transaminase level of the patients suffering from chronic virus hepatitis. Schisantherin E and deoxyschisandrin were not effective.


Primary hepatic pregnancy. Case report.

Primary hepatic pregnancy. Case report. A case of primary hepatic pregnancy presenting as a lithopedion in the right hypochondrium is presented. The lithopedion was removed and the patient recovered uneventfully. The diagnosis of primary hepatic pregnancy is briefly discussed.


Triage, education, and group meetings: efficient use of the interdisciplinary team with chronic psychiatric outpatients. The caseload of chronic patients of a large mental health outpatient clinic was triaged into medication groups with educational and socialization emphasis. Organization, division of staff responsibilities, and longitudinal clinic responses are described, and advantages and pitfalls of the group format are presented.


[Effect of stress on sleep characteristics in humans]. Earlier investigations of Baekeland et al. (1968) showed that stress conditions change the characteristic features of sleep. It was the aim of this work to compare the effect of pre-examination stress and preoperative stress on the characteristic features of sleep. Three groups of 5 individuals each were studied: students, patients and controls aged from 20 to 45 years. In all patients psychological investigations by the test of Cattel were carried out before each polygraphic recording. These investigations confirmed presence of anxiety prior to falling asleep in the groups of students and patients and its effect on the subsequent sleep. The most significant changes during stress were observed in paradoxical sleep (REM). The amount of this sleep is reduced during stress while its intensity increases significantly (phasic REM sleep period). Persistence of disturbances of sleep depends on the duration of stress stimulus. The stress reaction connected with examination was short-lasting and disappeared after passing the examination. In the group of patients the stress reaction was prolonged on the average 33 days after the operation.


Acute and chronic estradiol-17beta inhibition of LH release in prepubertal female pigs: time course and site of action. It has been demonstrated that 5.0 mug estradiol-17beta (E2) iv inhibits spontaneous episodic release (SER) of LH from 3-9 h after injection in immature female pigs (gilts). To understand this phenomenon we tested pituitary response (PR) to synthetic LH-RH/FSH-RH (LH-RH) for 13 h after identical E2 treatment in eight 7-8-week-old gilts. Using chronic cannulae PR was determined by measuring the change in plasma LH (delta LH) by RIA after iv injection of 2.0 mug LH-RH. PR was determined every 2 h starting 1 or 2 h before E2 or saline treatments. The PR prior to treatment was 4.3 plus or minus 0.3 ng/ml. By the second releasing-hormone challenge PR in controls was depressed, remaining at about 2.5 ng/ml thereafter. Compared with controls PR depression was greater (P less than 0.005) 1 h following E2 (delta LH = 1.0 plus or minus 0.4 ng/ml). Responsiveness then returned toward pretreatment levels and from 6 h post-treatment onward PR was not different from controls. Initial inhibition of SER may therefore be located in the pituitary and brain. However, after 4 h inhibition appears to be purely neural. Earlier studies showed that subcutaneous (SC) implants of E2 for 3 days in prepubertal gilts depressed PR to LH-RH. We further examined the effect upon PR of implants releasing physiologic levels of E2. PR was evaluated as above at 2-h intervals for 12 h after SC implantation of silastic capsules containing E2 (n = 6) or sham implant (n = 1); then every 6 h up to 54 h post-treatment. For the first 12 h PR depression in the control was identical to controls in the acute experiment; after 36 h PR was similar to pretreatment levels. In E2 implanted animals PR fell to a mean of 1.8 plus or minus 0.1 ng/ml, 4-12 h after implantation, then recovered, stabilizing at 2.3 plus or minus 0.1 ng/ml after 18 h. It is concluded that estrogen treatment rapidly causes a depression of pituitary response to exogenous LH-RH. This rapid effect may not be dependent on E2 dosage. The extent of recovery of pituitary responsiveness probably depends upon the level and persistence of the E2 treatment.


Stimulation of Adenosine 3',5'-monophosphate formation in incubated rat hypothalamus by estrogenic compounds: relationship to biologic potency and blockade by anti-estrogens. Several estrogenic compounds were examined for their abilities to stimulate the formation of adenosine 3',5'-monophosphate (cyclic AMP) in incubated hypothalami from immature (27-28 day old) female rats. 17-beta estradiol (E2) and diethylstilbestrol (DES) significantly increased the formation of cyclic AMP while estrone and estriol elicited small but not statistically significant increases in cyclic AMP formation. 17-alpha estradiol was ineffective in increasing cyclic AMP formation. The anti-estrogenic agent clomiphene was found to effectively antagonize the formation of cyclic AMP elicited by E2 and DES, while having no stimulatory effects  on cyclic AMP formation itself. These data indicate that the binding of estrogenic compounds to cytoplasmic sites (receptors) in the hypothalamus is required for subsequent stimulation of cyclic AMP formations.


Inflammatory fibrous polyp (pseudotumor) of ileum, a rare cause of intestinal obstruction. Inflammatory fibrous polyp of the ileum is a rare condition. This report adds one patient to the 11 previously reported. These lesions usually involve intermittent, colicky abdominal pain, often of several weeks duration and occasionally as a cause of acute intestinal obstruction. X-rays usually show small bowel obstruction or intussusception, but may be completely normal. The pathological diagnosis is seldom made before microscopic examination of resected specimens. They are clinically interpreted to be neoplasm and treated by segmental resection. No recurrences have been reported after treatment. Etiology is unknown.


Obstructing polyps of the posterior urethra in boys: embryology and management. Solitary fibrous polyps are in uncommon but important cause of obstructive uropathy, infection and hematuria in boys. The clinical presentation and management in 5 boys are discussed and the literature is reviewed. Emphasis is placed on the pitfalls in diagnosis and recent endoscopic techniques of treatment.


Stabilization and purification of glucosamine 6-phosphate isomerase from rat kidney. 1. Glucosamine 6-phosphate (GlcN-6-P) isomerase of rat kidney was resistant to heating at 50--55 degrees in crude extract but not after several purification steps. GlcN-6-P and N-acetylglucosamine 6-phosphate were found to stabilize the isomerase under these conditions. They also protected the enzyme from tryptic digestion, but only GlcN-6-P was effective against inactivation by p-chloromercuribenzoate. 2. When GlcN-6P isomerase was purified from fresh kidney and kidney stored at -20 degrees, separately and under GlcN-6-P, the two preparations were different in elution profile from a hydroxyapatite column. It was subsequently found that storage of crude extract at -20 degrees resulted in molecular alterations of the enzyme. Prolonged purification appeared to affect the enzyme similarly. The molecular alterations, however, were suppressed if the extract was stored at -70 degrees. 3. These findings have been utilized to develop a procedure, which enables us to purify rat kidney GlcN-6-P isomerase without any molecular alteration and in good yield.


Protein metabolism in uraemia.

Protein metabolism in uraemia. Protein metabolism in uraemia is reviewed. Very few, if any, disorders of amino acid metabolism can at present confidently be attributed to uraemia per se rather than to protein/energy deprivation. Retained urea nitrogen is recycled to the liver as ammonia; a proportion is reutilized for synthesis of non-essential amino acids and, if their carbon skeletons are supplied, for synthesis of essential amino acids. Practical applications of the reutilization of non-amino nitrogen in advanced chronic renal failure are being explored. Nevertheless, uraemic individuals readily become undernourished, and they should receive as much protein as their symptoms will permit.


Effects of polyunsaturated fats on lipid metabolism in patients with hypertriglyceridemia. Studies were carried out on the effects of polyunsaturated fats on lipid metabolism in 11 patients with hypertriglyceridemia. During cholesterol balance  studies performed in eight patients, the feeding of polyunsaturated fats, as compared with saturated fats, caused an increased excretion of endogenous neutral steroids, acidic steroids, or both in most patients. Increases in steroid excretions were marked in some patients and generally exceeded the decrement of cholesterol in the plasma compartment. The finding of a greater excretion of fecal steroids on polyunsaturated fats in hypertriglyceridemic patients contrasts to the lack of change in sterol balance previously reported for patients with familial hypercholesterolemia; however, other workers have found that polyunsaturated fats also enhance steroid excretion in normal subjects. In most of the patients, simultaneous studies were carried out on biliary lipid composition, hourly outputs of biliary lipids, and pool sizes of bile acids. In several but not all patients, fasting gallbladder bile became more lithogenic after institution of polyunsaturated fats. This increased lithogenicity was not due to a decrease in bile acid pools; in no case was the pool decreased by polyunsaturated fats. On the other hand, two patients showed an increased output of biliary cholesterol, and frequently there was an increase in fecal neutral steroids that were derived from cholesterol; thus, polyunsaturated fats may increase bile lithogenicity in some patients through mobilization of cholesterol into bile. Reductions in plasma cholesterol during the feeding of polyunsaturated fats was seen in most patients, and these changes were usually associated with a decrease in concentration of plasma triglycerides. In fact, the degree of cholesterol lowering was closely correlated with the extent of triglyceride reduction. Therefore, in hypertriglyceridimec patients polyunsaturated fats may contribute to cholesterol reduction by changing the metabolism of triglycerides or very low density lipoproteins. The findings of changes in the metabolism of cholesterol, bile acids, and triglycerides in the patients of this study suggests that polyunsaturated fats may cause a lowering of cholesterol through multiple mechanisms, and it seems unlikely that a single action can explain all the effects of these fats on the plasma lipids.


Cation flux in the ehrlich ascites tumor cell. Evidence for Na+-for-Na+ and K+-for-K+ exchange diffusion. In a previous study, evidence was presented for an external Na+-dependent, ouabain-insensitive component of Na+ efflux and an external K+-dependent component of K+ efflux in the Ehrlich ascites tumor cell. Evidence is now presented that these components are inhibited by the diuretic furosemide and that under conditions of normal extracellular Na+ and K+ they represent Na+-for-Na+ and K-+for-K+ exchange mechanisms. Using 86Rb to monitor K+ movements, furosemide is shown to inhibit an ouabain-insensitive component of Rb+ influx and a component of Rb+ efflux, both representing approx. 30 percent of the total flux. Inhibition of Rb+ efflux is greatly reduced by removal of extracellular K+. Furosemide does not alter steady-state levels of intracellular K+ and it does not prevent cells depleted of K+ by incubation in the cold from regaining K+ upon warming. Using 22Na to monitor Na+ movements, furosemide is shown to inhibit an ouabain-insensitive component of unidirectional Na+ efflux which represents approx. 22 percent of total Na+ efflux. Furosemide does not alter steady-state levels of intracellular Na+ and does not prevent removal of intracellular Na+ upon warming from cells loaded with Na+ by preincubation in the cold. The ability of furosemide to affect unidirectional Na+ and K+ fluxes but not net fluxes is consistent with the conclusion that these components of cation movement across the cell membrane represent one-for-one exchange mechanisms. Data are also presented which demonstrate that the uptake of alpha-aminoisobutyrate is not affected by furosemide. This indicates that these components of cation flux are not directly involved in the Na+-dependent amino acid transport system A.


Bathtub refinisher's lung: an unusual response to toluene diisocyanate. Immunologic and inhalation challenge studies were performed on a patient engaged in bathtub refinishing who developed systemic and respiratory symptoms suggestive of hypersensitivity pneumonitis temporally related to his occupation. The refinishing process used a catalyst containing toluene diisocyanate, and all clinical features of the disorder were reproduced by challenge. No immunologic mechanism could be identified. A change of occupation resulted in complete relief of symptoms.


Sex differences in the intramuscular absorption and bioavailability of cephradine. Six male and six female volunteers each received a single intramuscular injection of cephradine, a new cephalosporin antibiotic, once weekly for 3 consecutive weeks. The drug was injected into the gluteus maximus, vastus lateralis, or deltoid muscle groups. Injection sites were rotated each week so that each subject received an injection into each muscle. Pharmacokinetic evaluation of serum concentrations and urinary excretion data indicated a sex difference with respect to the rate and extent of cephradine absorption from the three injection sites. Smaller areas under the curve and absorption rate constants were observed for females after injection into each muscle group. The most striking difference was observed when cephradine was injected into the gluteus maximus muscle, where the exponential function describing the alpha phase was observed to be 1.16 +/- 0.17 hr(-1) for females and 2.70 +/- 0.34 hr(-1) for males. Total area under the mean serum concentration-time curves, mean time to peak, and peak height parameters consistent with the slower rate of absorption and lesser bioavailability in females were observed. These results show that the vastus lateralis or deltoid muscle groups are preferable to the gluteus maximus as injection sites because of the more rapid rates of drug absorption from those muscles.


Antibodies to Epstein-Barr viral capsid and early antigens associated with Burkitt's lymphoma and lymphoblastic lymphosarcoma in Israel. Before and/or after chemotherapy was administered to patients with Burkitt's lymphoma (BL) or lymphoblastic lymphosarcoma (LLS), their sera and those of matched controls were tested for antibodies to Epstein-Barr virus (EBV) capsid antigen (VCA) and early antigen by the indirect immunofluorescence method. Ten of the 16 BL patients were Arab children and 8 of the 11 LLS patients were Jews of Asian-African origin. Although half the BL patients did not have elevated antibody titers when their disease was diagnosed, significantly higher ones were detected in the BL group as compared with the LLS patients and their matched controls; Arab patients had the highest titers. IgM antibodies specific for VCA were found in 2 patients concurrently with elevated titers. We found no correlation between the clinical course of BL and the patients' antibody titers to EBV.


Inversion homozygosity of chromosome no. 9 in a higly inbred kindred. A pericentric inversion of chromosome no. 9 was present in seven of 10 members of a highly inbred kindred investigated; two were inversion homozygotes and five were heterozygotes. Inversion homozygosity was observed in both the propositus, ascertained because of ambiguous genitalia, and his phenotypically normal father. A phenotypically normal sister and brother with similar clinical findings proved to be inversion heterozygotes. These findings conclude that no causal relationship exists between the inversion and the abnormal phenotype.


Inhibition of carbonic anhydrase by parathyroid hormone and cyclic AMP in rat renal cortex in vitro. It has been demonstrated that parathyroid hormone (PTH) inhibits the proximal tubular reabsorption of bicarbonate, and increases the urinary excretion of that ion. There is also a qualitative similarity between the alterations of the proximal tubular reabsorption of phosphate, sodium, and water after PTH administration and after acetazolamide administration. These findings suggest that the renal effect of PTH is possibly mediated through the inhibition of carbonic anhydrase in proximal tubules. Therefore, a possible inhibitory effect of PTH on carbonic anhydrase was evaluated in the homogenate of rat renal cortex by an indicator titration method. Incubation of cortical homogenates with PTH for 10 min at 37degreesC inhibited carbonic anhydrase activity. The inhibitory effect of PTH was ATP-, Mg++-, and K+-dependent and temperature-dependent; inactivation of PTH by heating at 100degreesC abolished the effect of PTH both to activate adenylate cyclase and to inhibit carbonic anhydrase. Calcium 5 mM also partially abolished effects of PTH to activate adenylate cyclase and to inhibit carbonic anhydrase. The inhibitory effect of PTH on carbonic anhydrase was specific to renal cortex. Cyclic AMP, the intracellular messenger substance for PTH, also inhibited carbonic anhydrase in renal cortex. The cyclic AMP-induced inhibition was also Mg++ dependent and temperature dependent, and required preincubation at 37degreesC. But 5'-AMP, a metabolic derivative of cyclic AMP without its biological effect, had no inhibitory effect on carbonic anhydrase. All the above results are consistent with the hypothesis that PTH inhibits proximal tubular reabsorption of bicarbonate and phosphate through the inhibition of carbonic anhydrase, and that inhibitory effect is mediated through the cyclic AMP system.


Concanavalin A inhibits tissue factor coagulant activity. Concanavalin A (con A) is a potent inhibitor of coagulant activity of native tissue factor. Coagulant activity is recovered by addition of alpha-methyl-D-glucoside to inhibited tissue factor. Inclusion of alpha-methyl-D-glucose during incubation of con A with tissue factor preserves coagulant activity. These data suggest that con A interacts reversibly with a carbohydrate residue in such a way as to inhibit coagulant activity of the molecule. Purified tissue factor apoprotein has been recombined with mixed brain phospholipids or purified phospholipids (phosphatidyl ethanolamine or a mixture of phosphatidyl choline with phosphatidyl serine). These preparations were also completely but reversibly inhibited by con A. Thus, purified tissue factor apoprotein appears to donate the affected carbohydrate residue.


The cariogenicity of snack foods and confections. A survey of the relationship between caries prevalence and the consumption of sugar and other foods by man has been interpreted to show that snack foods share importance with sucrose in caries causation. Support for this conclusion is found in animal experiments and some in vitro and in vivo tests.


Quantitative studies of pinocytosis. II. Kinetics of protein uptake and digestion by rat yolk sac cultured in vitro. Pinocytic uptake of 125I-labeled bovine serum albumin by 17.5-day rat visceral yolk sac cultured in vitro has been examined. Uptake was followed by intracellular digestion and, after an initial period, the content of radioactivity in the tissue itself remained constant during the incubation. Radiolabel was returned to the culture medium predominantly as (125I)iodotyrosine; exocytosis of undigested protein did not occur. The rate of uptake of labeled protein, which was constant within an experiment and reproducible between experiments, was much higher than that of a nondigestible macromolecule, 125I-labeled polyvinylpyrrolidone. The higher rate of uptake was a consequence of the protein entering the cells chiefly by adsorption to the plasma membrane being internalized; 125I-labeled albumin did not stimualte, nor did 125I-labeled polyvinylpyrrolidone inhibit pinocytosis. Different preparations of 125I-labeled albumin had characteristically different rates of uptake, probably reflecting differences in affinity for plasma membrane receptors. The physiological significance of the findings is discussed.


A fine structure study of the anthocodium in Renilla mülleri. Evidence for the existence of a bioluminescent organelle, the luminelle. A fine structure study of the anthocodium of the sea pansy, Renilla mülleri, was undertaken. The anthocodium, a known site of bioluminescence, was selected in order to determine whether a structural entity could be found which would satisfy the biochemical and physiological features associated with the known sites of bioluminescence in this animal. These sites, termed lumisomes, have previously been shown to be small (0.1-0.2 mum), membrane-enclosed vesicles which contain all the proteins necessary for bioluminescence and its immediate control. One of the lumisomal proteins is an intensely green fluorescent protein and has been used as a probe for the detection of the cellular sites of bioluminescence. This green fluorescence was associated only with gastrodermal cells. We report the identification of a unique morphological entity, restricted to the cells of the gastrodermis, which satisfies the biochemical and physiological requirements for bioluminescence in Renilla. It is a large (4-6 mum), membrane-bounded subcellular organelle comparable in size to a subcellular structure whose green fluorescence is typically associated with the in vivo bioluminescence. Furthermore, it is filled with smaller membrane-bounded vesicles which have the same size and shape as the lumisomes. We suggest that the organelle identified in this study be termed a luminelle.


Beta-adrenergic blockade in diuretic-treated patients with essential hypertension. The influence of beta-adrenergic blockade (160 mg per day of propranolol for four weeks) on plasma renin activity, plasma volume, and arterial pressure was explored in 20 patients with essential hypertension with hyper-reninemia from long-term diuretic therapy. In 15 of these patients renin activity remained elevated (range, 3.1 to 23.0 ng per milliliter). Plasma volume was unchanged in eight, increased in 11 and reduced in one. In 17 subjects mean arterial pressure decreased by more than 10 mm Hg, but these impressive reductions could not be explained by quantitative changes in either renin activity (r equals 0.1) or plasma volume (r equals 0.1). These data suggest that suppression of plasma renin activity by beta-adrenergic blockade is not attainable during diuretic therapy and is not the major factor responsible for the antihypertensive action of propranolol.


Some unusual cases of apexification subsequent to trauma. Three cases are reported in which apexification occurred without the benefit of endodontic treatment. These reports illustrate that immature teeth which are avulsed and replanted, dislocated and repositioned, or traumatized with pulp necrosis supervening, may progress to form complete apices without intracanal therapy. The value of using calcium hydroxide is not in question, but may not be as essential an aid to apical closure as was previously thought. In one case, the appearance of isolated apixes forming, deep in the bone after loss of very immature lateral incisors poses the question of whether this event does not occur more frequently after extraction of newly erupted or young impacted teeth.


The protean manifestations of Crohn's disease. Crohn's disease is a perplexing disease with a high rate of morbidity and complications. The incidence appears to be increasing. The cause is unknown, and response to medical therapy has been disappointing. Diagnosis may be very difficult and often is delayed. A high proportion of patients eventually require surgery, and an appreciable percentage will have recurrence of disease afterward. The prognosis in terms of responsiveness to medical therapy is believed to be poorer than the prognosis of ulcerative colitis. A national cooperative study to assess drug therapy prospectively is under way.


Simple chronic constipation: pathophysiology and management. Chronic constipation is not a simple problem. It is often related to fundamental beliefs and habits. Once it has been established that the cause is not an organic disorder, the physician must take pains to explore with the patient other possible causes. Simple, inorganic constipation can usually be traced to poor diet or poor habits. The physician should provide simple explanations of the mechanisms involved in the act of elimination and detailed instructions on appropriate food and water intake and the development of regular habits. Laxatives should be prescribed only if absolutely necessary and if the patient taking them can be carefully observed.


Successful orthotopic allotransplantation of hearts from dogs in irreversible shock. The viability of the heart from irreversibly shocked dogs was evaluated. Thirty-one mongrel dogs were used to develop a uniformly lethal hemorrhagic shock model. The final model utilized a 30 mm. Hg mean arterial pressure with a 40 percent decompensation (uptake of reservoir blood). All control dogs subjected to this procedure died within 24 hours. Eleven hearts were transplanted following the shock procedure. Blood samples were drawn at intervals and analyzed for Po2, pH, glucose, oxygen content, and hematocrit. Cardiac outputs and ECG's were taken before and after transplant. All parameters measured returned to control levels following the transplants. Of the dogs receiving heart transplants, 10 survived more than 24 hours and eight survived more than 7 days. Compared with the survival of the shock model experiments, the survival of the transplant recipients was significant at the p less than 0.01 level. These results suggest that deterioration of the heart is not the factor which prevents recovery from irreversible hemorrhagic shock.


Assistants to primary physicians in California. The mid-level practitioner movement is no longer experimental; nurse practitioners and physician's assistants in California have proved to fill a necessary and viable professional role in the delivery of primary health care. The physician's assistant law (AB2109) and the Experimental Manpower Act (AB1503) have facilitated the training and functioning of these new health care professionals; more comprehensive laws are still needed to permit optimal utilization. National agencies for approval of teaching programs and testing of individual graduates will play an increasing role in the accreditation and certification procedures. Professional role difficulties, issues of sex and questions of delegation of responsibility are being resolved and it is hoped that a more equitable and patient-oriented system is evolving.


Aromatic amino acid hydroxylase inhibitors. 4. 3-Substituted alpha-methyltyrosines. In the present study a series of 3-alkenyl-alpha-methyltyrosines and their corresponding 3-alkyl-and dihydrobenzofuran analogs was synthesized for potential tyrosine hydroxylase (TH) inhibitory activity. The appropriately substituted hydantoins IIIa and IIIb, which were prepared from the corresponding allyloxybenzylhydantoins IIa and IIb through Claisen rearrangement, served as intermediates for the synthesis of these amino acids. TH inhibition was reduced upon either saturation of the double bond in the side chain or cyclization to form the dihydrobenzofuran analogs. Formation of the epoxide had a similar effect. The inhibitory activity of these compounds against aromatic amino acid decarboxylase (AADC) and dopamine beta-hydroxylase (DBH) was also investigated. Unsaturation, in both cases, decreases the inhibitory activity; however, the presence of a free phenolic group appears to be essential for AACD inhibitory activity.


Amidines and related compounds. 6. Studies on structure-activity relationships of antihypertensive and antisecretory agents related to clonidine. Correlations of antihypertensive and antisecretory activities with various structural modifications of the antihypertensive agent clonidine (2-(2,6-dichlorophenylimino)imidazolidine) are described. Eleven chemical classes of compounds containing an "amidine" moiety were prepared in this study. The antihypertensive activity of these compounds was evaluated in metacorticoid hypertensive rats and unanesthetized neurogenic hypertensive dogs following oral administration. Antisecretory activity was evaluated in fistula rats by measuring pH and volume of gastric secretion. Two compounds, 2-(2,6-dimethylphenylimino)imidazolidine and 2-(2,6-dichlorophenylimino)pyrrolidine, are particularly effective antisecretory agents with minimal antihypertensive activity.


Oxygen binding by hemocyanin from Levantina hierosolima. I. Exclusion of subunit interactions as a basis for cooperativity. The effect of oxygen on the distribution of hemocyanin from Levantina hierosolima among the three sedimenting species 20, 60, and 100 S was determined under two sets of experimental conditions: (a) at pH 7.63 in the absence of Ca2+, where oxygen binding in noncooperative; (b) at pH 8.20 in the presence of 2 x 10-3 M Ca2+, where oxygen binding is cooperative. A comparison of the results in the two cases eliminates the possibility that equilibrium between species with different oxygen affinities is responsible for the cooperative behavior. Cooperative oxygen binding was demonstrated for the 20S subunits at pH 8.80 and 1 x 10-3 M Ca2+. Under these conditions, the concentration of calcium is sufficient to affect the oxygen affinity, but the concentration of calcium plus proton is not sufficient to bring about association. The findings exclude interactions among 20S subunits as a basis for cooperativity in hemocyanin.


Oxygen binding by hemocyanin from Levantina hierosolima. II. Interpretation of cooperativity in terms of ligand-ligand linkage. Oxygen binding by hemocyanin from Levantina hierosolima was studied at pH 7.30, in solutions containing calcium in the concentration range 0-1 M. The binding was found to be cooperative, the degree of cooperativity being calcium concentration dependent. The dependence on calcium concentration of the affinity toward oxygen for both deoxygenated and oxygenated hemocyanin was interpreted in terms of two oxygen-linked calcium ions, one promoting and the other opposing oxygen binding. The results show that cooperativity may be fully explained on the basis of a coupling of the free energy of binding between calcium and oxygen.


Phase transitions and phase separations in phospholipid membranes induced by changes in temperature, pH, and concentration of bivalent cations. Differential scanning calorimetry (DSC) and fluorescence polarization of embedded probe molecules were used to detect phase behavior of various phospholipids. The techniques were directly compared for detecting the transition of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidic acid (DPPA) dispersed in aqueous salt solutions. Excellent agreement occurred in the case of phosphatidylcholine; however, in the case of phosphatidic acid, at pH 6.5, transitions detected by fluorescence polarization using the disc-like perylene molecule occurred about 10 degrees lower than those detected by DSC. Discrepancy between fluorescence and DSC methods is eliminated by using a rod-like molecule, diphenylhexatriene (DPH). Both techniques show that doubly ionizing the phosphate group reduces the Tc by about 9 degrees. Direct pH titration of fluidity can be accomplished and this effect is most dramatic when membranes are in their transition temperature range (ca. 50 degrees). Phosphatidic acid transitions occur at higher temperatures, and have appreciably lower transition enthalpies and entropies than phosphatidylcholine. These effect could not be explained simply on the basis of double layer electrostatics and several other factors were discussed in an attempt to rationalize the results. Addition of monovalent cations (0.01-0.5 M) is shown to increase the Tc of dipalmitoylphosphatidylglycerol by less than 3 degrees. However, addition of (1 x 10-3 M) Ca2+ abolishes the phase transition of both phosphatidyglycerol and phosphatidylserine in the range 0-70 degrees. Preliminary X-ray evidence indicates the phosphatidylserine-Ca2+ bilayers are in a crystalline state at 24 degrees. In contrast, 5 x 10-3 M Mg2+ only broadens the transition and increases the Tc indicating a considerable difference between the effects of Ca2+ and Mg2+. Neutralization of PS increases the Tc from 6 degrees (at pH 7.4) to 20-26 degrees (at pH 2.5-3.0) but does not abolish the transition, suggesting the Ca2+ effect involves more than charge neutralization. Addition of Ca2+ to mixed phosphatidylserine-phosphatidylcholine dispersions, induces a phase separation of the dipalmitoyl- (and also distearoyl-) phosphatidylcholine as seen by the appearance of a new endothermic peak at 41 degrees (58 degrees). Similarly, in mixed (dipalmitoyl) phosphatidic acid-phosphatidylcholine (2:1) dispersions, Ca2+ again can separate the phosphatidylcholine component.


Further studies on the subunit structure of Chromatium ribulose-1,5-phosphate carboxylase. Upon alkali exposure Chromatium ribulose-1,5-bisphosphate carboxylase dissociates into constituent subunits, a catalytic oligomer of the larger subunit, A8, and monomeric form of the small subunit B. By sedimentation equilibrium molecular weights of the native enzyme and the catalytic oligomer produced by an alkali treatment were estimated to be 5.11 x 10 5 and 4.29 x 10 5, respectively. To provide information on reversibility of the dissociation by determining whether the enzymically inactive small subunit B of the whole enzyme molecule did indeed exchange with exogenously added subunit B a radioisotopic method was used. After initial alkaline dialysis at pH 9.2 of a mixture of a nonlabeled native enzyme preparation and 14C-labeled subunit B, and the subsequent dialysis at pH 7.0, incorporation of 14C into the recovered native enzyme was determined. Without the alkaline treatment there was no detectable exchange, while after alkaline dialysis for 5 and 10 hr the subunit B exchange was 89 and 82%, respectively. Rabbit antiserum prepared against the catalytic oligomer of the spinach ribulose-1,5-bisphosphate carboxylase, anti-(A) (spinach), inhibited the Chromatium carboxylase and oxygenase activities. This result together with the identical immunoprecipitation lines on an agar plate formed between the antiserum and the Chromatium carboxylase and between the antiserum and the catalytic subunit of the Chromatium enzyme strongly indicated structural near identity of the catalytic subunits of the spinach and Chromatium carboxylase molecules. Results also show that the catalytic site of the Chromatium ribulose-1,5-bisphosphate carboxylase and oxygenase exists in the large polypeptide chain.


Cobalt and ruthenium replacement for iron in adrenal iron-sulfur protein (adrenodoxin). Preparation and some properties. The Co- and Ru-substituted derivatives of adrenal iron-sulfur protein (adrenodoxin) were prepared from its apoprotein in the presence of urea, dithiothreitol, Na2S, and metal ions. Both metal-substituted proteins had 2 g-atoms each of metal and labile sulfur per mole of protein. The Co derivative had optical absorption maxima at 257, 264, 470, and 1430 nm with shoulders at 275, 280, 300, and 380 nm. The molar extinction coefficient per Co atom was 2.200 M-1 cm-1 at 470 nm. The Ru derivative had a broad maximum at 500 nm with a molar extinction coefficient of approximately 100 M-1 cm-1 per Ru atom. The visible chromophore of the Co- and Ru-substituted proteins with mercurials revealed that the saturation levels are 8.6 and 8.4 mol of mercurial/mol of protein. The values agree with that of the native protein within experimental errors. The tyrosyl residue at position 82 displayed a broad anomalous emission at 335 and 331 nm for the Co- and Ru-substituted proteins, respectively, as well as in the case of the native protein. There was no electron paramagnetic resonance signal of the Co derivative in a wide magnetic field at 77 degrees K. Additionally, the Co and Ru derivatives had no enzymatic activity toward NADPH-cytochrome c reduction in the presence of adrenal diaphorase (adrenodoxin reductase). There was no indication that Mn, Ni, Cu, and Os are incorporated into the apoprotein in the presence of urea. Incorporation of Fe into the protein was examined in the presence of Co or Ru. In a system containing both Fe and Ru, Fe was exclusively incorporated into the protein. In contrast to this, the reaction products from a system containing both Fe and Co were found to consist of both Fe and Co derivatives at approximately equimolar quantity.


Diabetic crises in children treated with small doses of intramuscular insulin. A new regimen for the management of diabetic crises in children using small doses of intramuscular insulin and generous amounts of intravenous fluids has been devised. Insulin dosage was calculated from the patient's weight and was independent of the degree of hyperglycaemia. Minimum demands were made upon the laboratory.


Vascular responses to anaesthetic agents. Data have been presented showing that certain general anaesthetic agents such as halothane decrease the spontaneous activity of the rabbit anterior mesenteric portal vein and decrease the response of venous and aortic strips to exogenous noradrenaline. If these observations can be extrapolated to the intact animal they may indicate that the hypotension occurring with use of such agents may be due not only to cardiac effects but also to peripheral vasodilatation and muting of reflex sympathetic vasoconstriction. Although the response to noradrenaline is antagonized, this appears to be nonspecific effect and no evidence was found for interference with noradrenaline release nor for direct actions on beta-adrenegic receptors. While the thiobarbiturates increased spontaneous activity and tone of the rabbit anterior portal vein no evidence was obtained that this occurred through release of noradrenaline from tissue stores.


Concentration of lidocaine hydrochloride in newborn gastric fluid after elective caesarean section and vaginal delivery with epidural analgesia. Lidocaine concentrations were measured after vaginal delivery or Caesarean section with epidural anaesthesia in samples of maternal and umbilical blood and in newborn gastric contents. The pH of the gastric aspirate was also determined in a number of neonates. Gastric lidocaine concentrations were higher and the pH was lower after vaginal delivery in comparison to Caesarean section. A significant inverse correlation exists between gastric pH and gastric lidocaine concentration, Neonate gastric lidocaine concentration  was significantly higher than in maternal or umbilical venous plasma after vaginal delivery, but not after Caesarean section. Due to these differences, gastric lavage for the treatment of neonatal lidocaine intoxication may be more beneficial in reducing foetal systemic local anaesthetic concentration after vaginal than after elective abdominal delivery.


Pharmacokinetic mechanisms of drug interactions. Many patients require multiple-drug therapy, often under the supervision of several physicians, this increasing the risk of adverse drug effects. While drug interactions cannot always be conveniently categorized, familiarity with basic pharmacologic and pharmacokinetic principles permits the clinician to anticipate and avoid many of the more common and serious drug interactions. Most serious drug interactions involve one of the four pharmacokinetic processes governing drug behavior within the body: absorption, distribution, metabolism, and renal clearance. Knowledge of whether a drug is a weak acid or a weak base is clinically useful because it can alert the physician to the propensity for certain types of drug interactions.


Oxidizing action of purine N-oxide esters. A technique involving O-acetylation of purine N-oxide derivatives in buffered aqueous solutions has permitted studies of the reactivity of many compounds for which the O-acetyl derivatives are not otherwise available. The oxidizing properties of a variety of N-acetoxypurines have been measured through their ability to oxidize iodide ion ot iodine, a reaction which is representative of a more general oxidizing ability. Those esters that oxidize iodide ion also catalyze the autoxidation of sulfite, a property characteristic of radicals. The same esters also oxidize cysteine to cysteic acid and tryptophan, tyrosine, and uric acid to yet uncharacterized products. Their oxidizing reactivity was compared with the ability of the same esters to react as electrophiles in another assay that measured the rate of formation of pyridine substitution products. The sulfate ester of 3-hydroxyxanthine has been synthesized. Its reactivity is qualitatively the same as that of 3-acetoxyxanthine but proceeds at a higher rate. Syntheses of S-(8-xanthyl)-N-acetylcysteine,  8-(2-hydroxyethylthio)xanthine,  and 1-methyl-8-mehtylmercaptoguanine are also described.


Cyclic adenosine 3':5'-monophosphate phosphodiesterase activity in malignant and cyclic adenosine 3':5'-monophosphate-induced "differentiated" neuroblastoma cells. The regulation of cyclic adenosine 3:5-monophosphate (cyclic AMP) phosphodiesterase activity in homogenates of malignant and cyclic AMP-induced "differentiated" neuroblastoma cells was studied. Neuroblastoma cells of at least three mouse and one human clone had both the low (2 to 4 muM) and the high (66 to 106 muM) Km phosphodiesterase. In cyclic AMP-induced differentiated cells the values of Km were decreased, whereas the values of Vmax appeared to be slightly increased. Magnesium and manganese stimulated phosphodiesterase activity. Calcium, zinc, copper, mercury, ethylenediaminetetraacetic acid, and imidazole completely inhibited phosphodiesterase activity in malignant cells, whereas the above agents, except ethylenediaminetetraacetic acid, only partially inhibited enzyme activity in differentiated cells. Ethylenediaminetetraacetic acid completely reduced phosphodiesterase activity in differentiated cells. The pH optimum for phosphodiesterase activity was about 8 in both malignant and differentiated cells. The present studies show that the values of Km and Vmax and the sensitivity of phosphodiesterase activity to divalent ions change in cyclic AMP-induced differentiated neuroblastoma cells, and therefore we propose that the reverse may be true during malignant transformation of nerve cells.


Microsomal metabolism of nitrosoureas.

Microsomal metabolism of nitrosoureas. N, N-Bis (2-chloroethyl)-N-nitrosourea (BCNU) is a substrate for a microsomal enzyme of mouse liver. The reaction requires NADPH, and the product is 1, 3-bis (2-chloroethyl) urea. This activity is also found in mouse lungs but not in several other tissues. With reaction conditions under which BCNU is not chemically degraded, the Km for BCNU with liver microsomes is 1.7 mM; nicotine is a competitive inhibitor with a Ki of 0.6 mM. N-Methyl-N-nitrosourea is denitrosated in a similar reaction. N- (2-Chloroetyhy)- N-cyclohexyl-N-nitrosourea and N-(2-chloroethyl)-N-(trans-4-methylcyclohexyl)-N-nitrosourea are also substrates for microsomal enzymes, but the products of these reactions are ring-hydroxylated derivatives. The Km value for N-(2-CHLOROETHYL)-N-cyclohexyl-N-nitrosourea is 3.0 mM and that for N-(2-chloroethyl)-N-(trans-4-methylcyclohexyl)-N-nitrosourea is 1.0 mM. The hydroxylase activity is also present in lungs, but not in the other mouse tissues. The rates of microsomal metabolism of BCNU, N-(2-chloroethyl)-N-cyclohexyl-N-nitrosourea, and N-(2-chloroethyl)-N-cyclohexyl-N-nitrosourea, and N-(2-chloroethyl-N-(trans-4-methylcyclohexyl)-N-nitrosourea are fast enough to allow metabolism of large portions of administered doses before chemical decomposition of the drugs occurs.


The relationship between metabolism, DNA binding, and carcinogenicity of 15,16-dihydro-11-methylcyclopenta(alpha)phenanthren-17-one in the presence of a microsomal enzyme inhibitor. The mean latent period for skin tumor production by the carcinogen 15, 16-dihydro-11-methylcyclopenta [alpha] phenanthren-17-one (Compound IVb) in the mouse was 30 weeks for a dose of 60 mug/week and about 45 weeks for 60 mug/week, while at 0.6 mug/week, no tumors were observed during 100 weeks. Simultaneous administration of the closely related noncarcinogen (IVa) (54 mug/week) together with the carcinogen at 60 mug/week had no effect on the mean latent period. Simultaneous administration of a threefold quantity of the microsomal enzyme inhibitor 7, 8-benzoflavone (I) with the carcinogen at the highest dose increased the mean latent period to 38 weeks, while at the intermediate dose it completely suppressed tumor formation. Neither ketone IVa nor IVb bound covalently to calf thymus DNA in vitro without prior metabolic activation. After incubation with rat liver microsomes and NADPH in the presence of air, both ketones bound covalently to added DNA in vitro, the noncarcinogen (IVa) about four times more extensively than the carcinogen (IVb), roughly in proportion to the overall extents to which these ketones were metabolized. In contrast, overall metabolism of the carcinogen (IVb) was somewhat increased by the addition of a threefold quantity of the inhibitor (I) to the incubation mixture, but binding to added DNA was almost completely prevented. These results are discussed in connection with the hypothesis that cellular DNA is the target of the carcinogen (IVb) for tumor initiation.


Immunochemotherapy of transplantable Moloney leukemia with cyclophosphamide and allogeneic spleen lymphocytes and reversal of graft-versus-host disease with alloantiserum. Histoincompatible (H-2) spleen cells from C57BL/6 mice that were sensitized with Moloney sarcoma virus caused fatal graft-versus-host disease in BALB/c mice when the cells were used in conjunction with an immunosuppressive, chemotherapeutic dose of cyclophosphamide to treat transplantable Moloney virus-induced leukemia. When antiserum against the donor spleen cells was administered 2 days after immunochemotherapy, graft-versus-host disease was prevented, but no immunotherapeutic effect was observed. When the antiserum was delayed for 3 days or more, lethal graft-versus-host disease occurred. Substitution of Moloney sarcoma virus-sensitized BALB/c X C57BL/6 F1 (hereafter called CB6F1) spleen cells for C57BL/6 cells, in conjunction with cyclophosphamide, "cured" 70% of the treated mice (accumulated value of two experiments). When anti-CB6F1 serum (alloantiserum) was administered 2 days after immunochemotherapy, the immunotherapeutic effect was abolished. Alloantiserum was not able to reverse the immunotherapeutic effect 3 days postgrafting or later, and there resulted a high percentage of long-term survivors. About two-thirds of the cured mice had positive donor-specific gamma-globulin titer 8 weeks postgrafting.


In vitro metabolic conversion of aflatoxins and benzo(alpha)pyrene to nucleic acid-binding metabolites. An aflatoxin B1 metabolite was found to become covalently bound to rat liver RNA and calf thymus DNA in vitro, and it formed complexes with increased spectral absorbance in the 360 nm region. The formation of such complexes was reduced nicotinamide adenine dinucleotide phosphate and microsome dependent, was inhibited by theta-diethylaminoethyl diphenylpropylacetate-HC1, and by CO and N2, when the latter were used to replace the gas phase of the incubations. The formation of the complexes was enhanced about 2-fold with cicrosomes from phenobarbital-treated rats but not from 3-methylcholanthrene-treated rats. More binding was observed with DNA than RNA. Dentured DNA was about 70% as effective as native DNA. Nucleic acids from various sources showed the following order of binding potency: DNA from Micrococcus luteus greater than DNA from calf thymus equal to DNA from rat liver greater than RNA from rat liver greater than transfer RNA from rat liver. In the presence of reduced nicotinamide adenine dinucleotide phosphate and microsomes from phenobarbital-treated rats, aflatoxin G1 was also converted into metabolite(s) that became covalently bound to nucleic acids and formed complexes with increased spectral absorbances in the 360 nm region: this reaction was also inhibited by theta-diethylaminoethyl diphenylpropylacetate-HC1. Under the same conditions, aflatoxin B2, aflatoxin G2, aflatoxin B2a, and "Compound 11," which lack a C2-C3 double bond, did not show any noticeable binding to either DNA or RNA. These data strongly support the concept that the microsomal mixed-funciton oxygenase-catalyzed oxidation of the C2-C3 double bond of aflatoxins is a prerequisite for the formation of nucleic acid-binding metabolites. Microsomes from untreated, phenobarbital-treated, and 3-methylcholanthrene-treated rats were compared in vitro for their ability to catalyze the formation of DNA-binding metabolites from aflatozin B1 and benzo(a)pyrene. In assays involving benzo(a)pyrene, microsomes from 3-methylcholanthrene-treated rats were 12- and 5-fold more active than microsomes from untreated and phenobar-bital-treated rats, respectively. This is in contrast to the results obtained with aflatoxin B1 and suggests that different enzymes in the hepatic microsomal mixed-function oxygenase complex are involved in the generation of reactive metabolites from various polycyclic hydrocarbons.


Tumor rejection in experimental animals treated with radioprotective thiols. In experimental animals, a systemic treatment with thiols of the mercaptoalkylamine type has affected all of five solid tumors so far investigated. (Three of the tumors were transplanted into the strain of origin.) There was either inhibition of growth or "oncodieresis," i.e., a necrosis and sloughing of tumors conducive to full recovery and repair. Mercaptoalkylamines and derivatives of the type used in our experiments are known to bind to cellular sites by a two-point attachment involving both thiol and amino groups. One of these compounds, cysteamine, was active in its native, unsubstituted form, but did not bring about oncodieresis when either the amino or thiol group, or both, were alkylated. Mercaptopropylamine, the 3-carbon homolog of cysteamine, was less active. Cystamine, a disulfide dimer of cysteamine that has no free reactive  sulfhydryl, did not induce any reaction. Thioglycerol, lacking a terminal amino group, had only negligible activity. Rejection was much more striking when treatment was started on the day of inoculation than when started 7 days later. Male mice rejected better than females. Results were inferior when tow of the agents were given simultaneously or together with other radioprotectants, such as L-cysteine, glutathione, dimethyl sulfoxide, or reserpine. Tumor rejection was enhanced when the phosphorylated thioyls, S-2-(3-aminopropylamino)ethylphosphorothioic acid or S-(2-ethylguanidine)phosphorothioci acid, were given simultaneously with the radioprotective serotonin, but there was no synergy of serotonin with the nonphosphorylated compounds S-2-aminoethylisothiouronium bromide or cysteamine. Serotonin alone did not affect the tumors.


Testosterone 5alpha-reductase in rat skin homogenates: measurement in the skin at various anatomical sites in males and females. Experiments were disigned to find suitable conditions to determine the  5alpha-reducatase activity in rat skin homogenates. The dihydrotestosterone formation was linear until 15 min. The 5alpha- reductase was very heat labile at 37-c in absence of testosterone and NADPH since complete loss of activity occurred after one hour of preincubation. At OC, there was a 20% decrease after 5 hr. The enzyme activiity was measured in the skin at various anatomical sites. It was found to vary with each region in the following order in the male; tail,greater than scrotum greater than ear greater than genital skin greater than dorsum smaller than or equal to thorax greater than sole of the foot. In a few tissues, the enzyme activity was higher than in the prostate. Corresponding female tissues exhibited lower reductase activity except the sole of the foot in which the contrary was found. This significant sex difference indicates that sex hormones may be involved in the control of the levels of that enzyme in rat skin.


Recurrent keratitis due to Acremonium potronii. In a 15-year-old boy a culture-proved keratitis after a corneal perforation healed without antifungal agents after corneal suturing and application of tissue glue. Eight months later a posterior corneal abscess developed. Diagnostic and therapeutic penetrating keratoplasty was performed when the lesion failed to respond to pimaricin. Cultures were positive for Acremonium potronii, the same fungus isolated from the original corneal laceration eight months previously. To our acknowledge, this is the first case report of a central corneal ulcer or abscess due to this specific organism.


Splanchnic hemodynamic response to passive hyperventilation. Two groups of anesthetized, splenectomized, and paralyzed dogs were hyperventilated (Vt 40 ml/kg). Normocapnia was maintained in one group (mean Paco2 37.6 mm"h'g, mean p"h '7.41) and respiratory alkalosis (mean Paco2 8 mmHg, mean pH 7.75) in the other. Splanchnic hemodynamic responses were similar in both groups. Average hepatic venous pressure increased from 3.2 to 6.4 mmHg in the normocapnic group and from 3.8 to 7.7 mmHg in the hypocapnic group. Average portal venous pressure increased from 10.7 to 12.0 mmHg and 10.8 to 12.7 mmHg in the normocapnic and hypocapnic groups, respectively. Mesenteric vascular resistance increased in 93 per cent of dogs. A decrease in functional intestinal capillary surface area during hyperventilation was indicated by a significant reduction in mesenteric Vo2 (from 15 to 11 ml/min, average 30 per cent), and a concomitant reduction in mesenteric O2 extraction ratio. Changes in mesenteric Vo2 were reflected in calculated splanchinic Vo2. Hepatic O2 uptake was essentially unchanged by tidal hyperventilation with or without hypocapnia.


Blood P50 calculated from a single measurement of pH, PO2, and SO2. P50 was calculated from a single measurement of pH, Po2, and So2 at a known temperature in 135 blood samples from 21 normal nonsmokers and eight patients. In the 92 blood samples with So2 between 20 and 90 per cent, the standard deviation of repeated calculated P50's on the same sample of blood at different So2 was plus or minus 1.0 Torr. Below So2 of 20 per cent and above So2 of 90 per cent, the standard deviations were plus or minus 5.5 and plus or minus 2.4 Torr, respectively. Combined measurement errors of plus or minus 1 Torr in Po2, plus or minus 1 percent in So2, plus or minus 0.01 in pH, and plus or minus 0.1 degree C in temperature are sufficient to explain the observed variation in calculated P50 in 90 per cent of 135 blood samples from 29 subjects and account for the greater observed variation at So2 less than 20 per cent and greater than 90 per cent.


Oxygen delivery and utilization in dogs with a sublethal dose of cobalt chloride. Four groups of eight dogs each were anesthetized with pentobarbital, paralyzed with succinylcholine, and ventilated at constant rate. Control measurements were made for 30 min, then 15 mg/kg of cobaltous chloride was given slowly intravenously to one group. A second group was also given 1 mg/kg per h propranolol (beta-block); a third group was given NaHCO3 to correct pH changes after CoCl2; and a fourth group had both beta-block and NaHCO3. Vo2 was measured every 10 min for 4 h and blood was taken frequently for lactate, pyruvate, and blood gas measurements. Cobalt transiently decreased Vo2 in all groups but significantly more in those with beta-block (groups 2 and 4). Cardiac output and mean arterial pressure were also decreased in all groups but to similar extent. Recovery of Vo2 was complete, usually within 60 min with little evidence of deficit repayment. Total O2 transport (Q X Cao2) appeared to limit Vo2 below 12 ml/kg times min. Above that value, histotoxic effects of CoCl2 reduced Vo2 approximately 20%. Excess lactate (XL) in arterial blood was linearly correlated with measured O2 deficit during the acute reaction of CoCl2, in all but group 3, similar to results previously obtained in hypoxic hypoxia.


Effect of positive-pressure breathing on aADN2 in hyaline membrane disease. In seven subjects with hyaline membrane disease and breathing 40-70% oxygen in nitrogen, the effect of continuous positive-pressure breathing (CPPB) was examined by application of a continuous negative pressure (10 cm water) about the thorax and assessment of the alveolar-arterial tension differences for nitrogen (aADn2) and oxygen (AaDo2). On CPPB, there was a decrease in the aADn2 by a mean 9 mmHg and a decrease in the AaDo2 by a mean 44 mmHg. This corresponded to a decrease in the total venous admixture (Qva/Qt) of 0.20 and to a decrease in the venous admixture due to a true right-to-left shunt (Qs/Qt) of 0.19. These data were interpreted to mean a significant improvement in Va/Qc imbalance within open ventilated parts of the lung, which could be responsible, particularly by relief of local alveolar hypoxia, for reduction of the pulmonary vascular resistance and the true right-to-left shunt.


The transport of sulfate ions across the membrane of the Ehrlich ascites tumor cell. The applicability of the membrane fixed charge hypothesis to anion transport in Ehrlich ascites tumor cells was studied by investigating the dependence of steady state sulfate transport on the extracellular pH, chloride and sulfate concentration. When the extracellular sulfate was maintained at 10 mM both cellular sulfate and sulfate transport increased with decreasing pH and chloride concentration. The dependence of sulfate transport on the cellular sulfate concentration suggests a saturation phenomenon. The relationship between sulfate transport and cellular sulfate was also studied as a function of extracellular sulfate, both in the presence and absence of chloride. In both cases, sulfate transport is a saturable function of the cellular sulfate. However, in the presence of chloride the maximal flux is twice that in its absence. The discrepancy between the maximal fluxes suggests that the transport system mediates chloride-sulfate exchange in addition to sulfate self exchange. Unidirectional sulfate effluxes into chloride and sulfate-free medium; into 50 mM sulfate medium or 50 mM chloride medium were: 0.38, 1.95 and 3.91 nmoles/10-7 cells min-minus1, respectively. These results indicate that in the absence of either sulfate or chloride the net efflux of sulfate is low. However, chloride or sulfate on the trans side of the membrane is effective in accelerating unidirectional sulfate efflux. Taken together, the results of this investigation cannot be explained in terms of the membrane fixed charge hypothesis. Rather, they support the contention that sulfate transport across the tumor cell membrane is a carrier-mediated process.


Influence of mono- and multivalent cations on the electrokinetic properties of Rana pipiens kidney cells. Changes in the cation composition of the ambient cell environment, at constant ionic strengths, altered the electrokinetic properties of the surface of normal adult Rana pipiens kidney cells in a manner which reflected its valence. the effect was expressed in the changes of the magnitude of the net surface charge, at any pH, and in the shift of the isoelectric point of the cell surface.


Characterization of the ATP-phosphohydrolase activity of bovine spermatozoa flagellar extracts. The ATP-phosphohydrolase activity of extracts prepared from bovine spermatozoa flagella (BSFE), was characterized with respect to enzyme, substrate, activator ion and salt concentration, temperature dependence and time stability. BSFE required the presence of a divalent cation for activity: Mg++ or Ca++ could function as activator; Mn++, Zn++ and Cd++ could not. EDTA, but not EGTA, was inhibitory to enzymatic activity. Ca++ inhibited the Mg++ stimulated activity. ATP was dephosphorylated more rapidly than GTP greater than CTP greater than ITP, and ADP was dephosphorylated at 40% of the rate of ATP. The magnesium activated ATPase was stimulated by potassium and inhibited by sodium ions. Activation of BSFE ATP-phosphohydrolase was maximal in the presence of Mg++ and ATP in equimolar concentrations and K+ (0.05-0.3 M) at 30 degrees C. Although the enzymatic activity of the extract was found to decrease rapidly with time, it could be maintained for up to three days by the addition of 2-beta-mercaptoethanol to the bovine spermatozoa flagellar extracts.


Influence of an experimental sodium fluoride dentifrice on dental caries incidence in children. Schoolchildren residing in a fluoride-deficient area were provided either a sodium fluoride (0.1% F) or a nonfluoride dentifrice for home use. About half the children provided each type of dentifrice were also given an initial prophylaxis. Combining the data with regard to the type of dentifrice indicated that the sodium fluoride dentifrice resulted in dental caries reductions of 24 and 26% as noted by the two examiners, respectively.


Studies on Ca2+-stimulated adenosine triphosphatase in rat submandibular glands: its distribution and properties. Intracellular distribution and some characteristics of a Ca2+-stimulated adenosine triphosphatase (ATPase) in rat submandibular glands were investigated. This enzyme was activated by calcium alone, and magnesium was not necessary for its activation. Mg2+-stimulated ATPase also was investigated in the same enzyme preparations.


Formation of CaHPO4-2H2O in tooth enamel as an intermediate product in topical fluoride treatments. Significant amounts of CaHPO4-2H2O (DCPD) were deposited in tooth enamel by pretreatment with a solution saturated with respect to DCPD. When these enamel samples were treated with a given fluoride solution, the fluoride uptake increased with increasing amounts of DCPD produced by the pretreatment. The interactions between enamel and acidic solutions to yield DCPD can be understood as dissolution-precipitation reactions and analyzed through the use of solubility phase diagrams.


Postdevelopmental effects of boron, fluoride, and their combination on dental caries activity in the rat. Drinking water of rats aged 21 days was supplemented with 1, 10, 30, 50, 100, or 283 ppm of boron or 10 or 25 ppm of fluoride individually or in combination. All rats were fed a cariogenic diet. Boron did not reduce dental caries activity in erupted molars after eight weeks. When given in combination, it partially antagonized the cariostatic effect of fluoride.


Phytate destruction by yeast fermentation in whole wheat meals. Study of high-extraction rate meals. Destruction of phytate by yeast fermentation is compared in sponges prepared from Iranian whole wheat meals of different extraction rates. Phytate was destroyed rapidly in whole meals of 75 to 85 and 85 to 90 per cent extraction, but destruction was retarded in those of 95 to 100 per cent extraction. Production of acid-soluble phosphorus kept pace with phytate destruction in the two whole meals of lower extraction rates but was delayed with less-than-expected yield in those of 95 to 100 per cent rate. Unleavened whole meal bread contains little acid-soluble phosphorus. Leavened breads made from whole meals of slightly lower extraction rate average five times as much. Since phytate phosphorus appears to remain unavailable in the small intestine in many circumstances, dependece on unleavened whole meal bread may result in critically low intakes of available phosphorus when other sources are lacking in the diet. It is concluded that replacement of the whole meals of 95 to 100 per cent extraction rate, presently the main staple of the diet of rural Iran, by those of somewhat lower rate is an important preliminary to the introduction of leaven and fermentation into village bread-making methods.


Autoradiographic study of mouse spermatozoan arginine-rich nuclear protein in fertilization. General labeling of ripe mouse spermatozoa was obtained two weeks after six injections of L-arginine-5-3H monohydrochloride, administered within two days. Besides tail labeling a very intensive nuclear labeling was obtained. It is presumed that this nuclear labeling represents almost exclusively tritiated arginine incorporation into basic nuclear protein. Mouse oocytes were fertilized in vitro with such labeled spermatozoa. It was found that the nuclear label is lost very early during male pronucleus formation, probably concomitantly with sperm chromatin decondensation. This might indicate total loss of the basic spermatozoal nuclear protein before male genome activation.


Micropuncture analysis of the cellular mechanisms of electrolyte secretion by the in vitro rabbit pancreas. Micropuncture techniques have been used to study electrolyte secretion by the spontaneously secreting in vitro rabbit pancreas over a wide range of environmental conditions. Pancreatic secretion does not have a strong requirement for HCO3 and secretion continues at nearly normal rates when exogenous HCO3 is replaced by acetate. Acetate concentration in the juice averages 70 meq/liter, nearly three times the environmental concentration. The similar characteristics exhibited by HCO3 and acetate secretion indicate that they are secreted by a common mechanism involving active H transport. In vitro acid-base alterations demonstrate that the secretion rate is controlled by the environmental HCO3 concentration and to a much lesser extent by the pCO2. Secretion also requires active Na transport across the mucosal membrane. The effects of ouabain and a low Na environment strongly suggest coupling between the transport of Na and H and a cellular mechanism for electrolyte secretion is proposed involving Na-H exchange mechanisms at both the mucosal and serosal membranes.


Role of calcium in volume regulation by dog red blood cells. Dog red blood cells (RBC) are shown to regulate their volume in anisosmotic media. Extrusion of water from osmotically swollen cells requires external calcium and is associated with net outward sodium movement. Accumulation of water by osmotically shrunken cells is not calcium dependent and is associated with net sodium uptake. Net movements of calcium are influenced by several variables including cell volume, pH, medium sodium concentration, and cellular sodium concentration. Osmotic swelling of cells increases calcium permeability, and this effect is diminished at acid pH. Net calcium flux in either direction between cells and medium is facilitated when the sodium concentrations is low in the compartment from which calcium moves and/or high in the compartment to which calcium moves. The hypothesis is advanced that energy for active sodium extrusion in dog RBC comes from passive, inward flow of calcium through a countertransport mechanism.


Improved growth media for Vibrio succinogenes. Five new culture media for Vibrio succinogenes are described. Of these, a medium composed of 0.4% yeast extract, 100 mM ammonium formate, 120 mM sodium fumarate, and 0.05% sodium thioglycolate, pH 7.3, supports the best growth.


Isolation of thermophilic fungi from snuff. Fourteen samples of retail purchases of snuff were examined for the presence of viable thermophilic fungi; four species were found.


Development of a simple method for concentrating enteroviruses from oysters. The development of a simple method for concentrating enteroviruses from oysters is described. In this method viruses in homogenized oyster tissues are efficiently absorbed to oyster solids at pH 5.5 and low salt concentration. After low-speed centrifugation, the supernatant is discarded and viruses are eluted from the sedimented oyster solids by resuspending them in pH 3.5 glycine-buffered saline. The solids are then removed by low-speed centrifugation, and the virus-containing supernatant is filtered through a 0.2-micronm porosity filter to remove bacteria and other small particulates without removing viruses. The virus-containing filtrate is then concentrated to a volume of a few milliliters by ultrafiltration, and the concentrate obtained is inoculated directly into cell cultures for virus assay. When tested with pools of oysters experimentally contaminated with small amounts of different enteroviruses, virus recovery efficiency averaged 63%.


Agar plate method for detection and enumeration of alkylbenzenesulfonate-degrading microorganisms. A simple method for detection and enumeration of alkylbenzenesulfonate (ABS)-degrading microorganisms by using agar plates was developed and used in microbiological studies of coastal marine and polluted river waters. The method depends upon the color responses of neutral red in alkaline medium. Neutral red changes from pink, when it enters into ABS micelles, to yellow, when the ABS is degraded, and does not form micelles. When neutral red-tris(hydroxymethyl)-aminomethane buffer solution and then cationic surfactant solution were sprayed onto the agar surface of ABS-nutrient agar cultures, transparent haloes appeared around the colonies of ABS-degrading microorganisms against a pink background. Viable counts of ABS-degrading bacteria isolated from both seawater and freshwater environments were considerably higher in polluted waters than in less polluted areas. Viable counts of ABS-degrading bacteria averaged 1.5 x 105/ml in samples from the surface water of polluted Tokyo Bay and 3.0 x 104/ml in samples from the surface water of polluted Tamagawa River but were fewer in number in samples from less polluted waters.


Biological modification of trichothecene mycotoxins: acetylation and deacetylation of deoxynivalenols by Fusarium spp. Attempts were made to elucidate the acetyl transformation of novel trichothecene mycotoxins, 3a,7a,15-trihydroxy-12,13-epoxytrichothec-9-en-8-one (deoxynivalenol) and its derivatives, by trichothecene-producing strains of Fusarium nivale, F. roseum, and F. solani. In the peptone-supplemented Czapek-Dox medium, F. roseum converted 3a-acetoxy-7a,15-dihydroxy-12,13-epoxytrichothec-9-en-8-one (3-acetyldeoxynivalenol) to deoxynivalenol. 3-Acetyldeoxynivalenol was also deacetylated by intact mycelia of the three strains in sugar-free Czapek-Dox medium. The growing F. nivale acetylated deoxynivalenol to afford a small amount of 3-acetyldeoxynivalenol. 3a,7a,15-Triacetoxy-12,13-epoxytrichothec-9-en-8-one (7,15-diacetyl-deoxynivalenol), which was then deacetylated to give 7a-acetoxy-3a,15-dihydroxy-12,13-epoxytrichothec-9-en-8-one (7-acetyldeoxynivalenol). It was noted that the ester at C-7 was not hydrolyzed by the fungal mycelium.


Simple process for the reduction in the nucleic acid content in yeast. A simple one-step process for the nucleic acid reduction in Rhodotorula glutinis is described. The process consists of submitting the yeast cells to a heat treatment in an acidic (pH 2) spent medium. The optimal temperature for pH 2 medium is 90 C and the final nucleic acid content in treated yeasts was 1.2%. Heat treatment at acidic pH is preferred to that at alkaline pH because it offers a better protection for amino acids and crude protein, while being more efficient in lowering the nucleic acid level. The new process is economic and rapid and could be easily used for industrial application.


Effect of pH and sodium chloride on growth of Bacillus cereus in laboratory media and certain foods. The effects of NaCl concentration, pH, and water activity (aw) on the ability of vegetative cells of Bacillus cereus to initiate aerobic growth in brain heart infusion broth at 30 C were studied in a factorial design experiment. By using multiple regression techniques, equations were derived which related the decimal reduction of the bacterial population to the concentration of NaCl and pH of broth to which the population was exposed. From these equations, the percentage of inoculated cells capable of initiating growth could be calculated. The reliability of these equations in foods was tested in laboratory-processed meat and rice media. The foods were less inhibitory than the broths, so that accurate prediction of growth initiation in foods was not possible by using the developed formulas. The impact of this type of quantitative study on the development of specific microbial standards for foods is discussed. When the NaCl concentration is increased, the aw is decreased and, with increased deviation of pH from optimum, more concentrated inoculum of B. cereus cells is needed to assure initiation of growth in culture media and foods.


Beta-galactosidase of Propionibacterium shermanii. Ten strains of Propionibacterium shermanii were tested for beta-galactosidase (beta-gal) activity. Of these ten strains, five yielded enhanced enzyme activity when cell suspensions were treated with toluene-acetone; on solvent treatment, the remaining five lost a considerable portion of the activity found in whole-cell suspensions. By using a strain yielding decreased activity upon solvent treatment, explanations for the loss in activity were sought through assays for possible alternative beta-galactoside utilization mechanisms. When this strain was assayed for beta-D-phosphogalactoside galactohydrolase by using orthonitrophenyl-beta-D-galactopyranoside-6-P04 as a substrate, the activity was wither lower or indiffernt as compared with beta-gal activity determined simultaneously. Cell suspensions of P. shermanii 7 and 22 (strains chosen for further work) grown separately on the individual substrates (lactose, glucose, galactose, and sodium lactate) did not show significant differences in beta-gal activity. Optimal temperature for beta-gal activity in untreated and toluene-acetone-treated cell suspensions of strain 7 was 52 C. With strain 22, of the temperatures tested, maximal activity in untreated cell suspensions was noted at 58 C and with solvent-treated cells at 32 C. In the cell-free extract (CFE) system, both strains exhibited maximal activity at 52 C. Optimal pH for untreated and solvent-treated cell suspensions of both strains was around 7.5. In the P. shermanii 22 CFE system, maximal activity occurred at pH 7.0; pH had very little effect on enzyme activity in P. shermanii 7 CFE. Sodium or potassium phosphate buffers in the assay system yielded the best activity. In the CFE system of these two strains, Mn2+ was definitely stimulatory, but in untreated and solvent-treated cell systems of these strains presence or absence of Mn2+ in the assay system had variable effects on enzyme activity. Maximal beta-gal activity was noted in P. shermanii 7 cells harvested after 28 h of growth at 32 C in sodium lactate broth. Sulfhydryl-group blocking agents inhibited enzyme activity in P. shermanii 22 CFE; the inhibition was partly reversed by dithiothreitol.


Plaque production by arboviruses in Singh's Aedes albopictus cells. We report plaquing tests of 124 virus strains, mostly arboviruses of 21 serological groups, in Singh's line of Aedes albopictus cells. Thirty of these plaqued: all were arboviruses of six groups and were known or presumed to be mosquito borne. Failing to plaque were 86 strains of arboviruses, mostly tick borne, two strains of insect pathogens, and six animal viruses not classified as arboviruses. Among mosquito-borne agents, plaquing ability appeared related to serological classification. California group and most A-group viruses failed to plaque, but nearly all members of B and Bunyamwera groups readily plaqued. Within serological group B, 14 of 16 mosquito-borne agents plaqued, but none of 13 tick-borne or vector-unassociated viruses did so. Some implications of these results for recognition and classification of arboviruses are discussed.


Renal conservation of ketone bodies during starvation. Renal handling of acetoacetate and beta-hydroxybutyrate was studied in 12 obese subjects undergoing total starvation. Simultaneously, the acetoacetate, beta-hydroxybutyrate, and inulin clearance rates were measured, and acetoacetate and beta-hydroxybutyrate reabsorption rates were calculated. Renal clearance of blood acetoacetate and beta-hydroxybutyrate remained constant. In contrast, acetoacetate reabsorption rate increased significantly from 47 plus or minus 10 mumoles/min on day 3 to 106 plus or minus 15, 89 plus or minus 10, and 96 plus or minus 10 mumoles/min on days 10, 17, and 24, respectively. Similarly, beta-hydroxybutyrate reabsorption rate increased significantly from 154 plus or minus 27 mumoles/min on day 3 to 419 plus or minus 53, 399 plus or minus 25, and 436 plus or minus 53 mumoles/min on days 10, 17, and 24, respectively. Both acetoacetate and beta-hydroxybutyrate reabsorption rates increased linearly when plotted against their filtered loads. Thus, no tubular maximal transport rate exists for acetoacetate or beta-hydroxybutyrate during physiologic ketonemia. Conservation 450-500 mmoles of ketone bodies/day prevents large urinary losses of cations during prolonged starvation. Since ammonium becomes the major cation excreted during prolonged fasting, the increased renal reabsorption of ketone bodies minimizes body protein loss and aids in maintaining high circulating acetoacetate and beta-hydroxybutyrate concentrations.


Optimum end-expiratory airway pressure in patients with acute pulmonary failure. To determine whether in the management of pulmonary failure, the maximum compliance produced by positive end-expiratory pressure coincides with optimum lung function, 15 normovolemic patients requiring mechanical ventilation for acute pulmonary failure were studied. The end-expiratory pressure resulting in maximum oxygen transport (cardiac output times arterial oxygen content) and the lowest dead-space fraction both resulted in the greatest total static compliance. This end-expiratory pressure varied between 0 and 15 cm of water and correlated inversely with functional residual capacity at zero end-expiratory pressure (r equal -0.72, p less than or equal to 0.005). Mixed venous oxygen tension increased between zero end-expiratory pressure and the end-expiratory pressure resulting in maximum oxygen transport, but then decreased at higher end-expiratory pressures. When measurements of cardiac output or of true mixed venous blood are not available, compliance may be used to indicate the end-expiratory pressure likely to result in optimum cardiopulmonary function.


Uptake and efflux of 14-C-dopamine in platelets: evidence for a generalized defect in Parkinson's disease. Thirty-five parkinsonian patients (five untreated, six with levodopa only, seven with levodopa plus Ro 4-4602, nine with anticholinergic and/or antihistaminic medication, and eight with the anticholinergic/antihistaminic medication plus amantadine) and 35 age-matched control subjects were studied. Platelets isolated from each individual plasma were incubated with 14C-dopamine. Uptake was found to be decreased to a significant degree in all treated or untreated parkinsonian patients when compared with control subjects. Anticholinergic and/or antihistaminic medication, with or without amantadine, further decreased the dopamine uptake into platelets, while levodopa alone or with Ro 4-4602 returned uptake values to near normal. Dopamine efflux paralleled exactly the uptake values. The fact that parkinsonian platelets exhibit impaired dopamine uptake, while age-matched control platelets do not, constitutes the first direct evidence in favor of a generalized dopamine defect in Parkinson's disease.


The syndrome of systemic carnitine deficiency. Clinical, morphologic, biochemical, and pathophysiologic features. An 11-year old boy had had recurrent episodes of hepatic and cerebral dysfunction and underdeveloped musculature. Overt weakness developed at age 10. Lipid excess, especially in type I fibers, was found in muscle. Hypertrophied smooth endoplasmic reticulum and excessive microbodies were present in liver. Marked carnitine deficiency was shown in skeletal muscle, plasma, and liver. Ketogenesis was impaired on a high fat diet, but omega oxidation of fatty acids was enhanced. There was excessive glucose uptake and essentially no oxidation of labeled long-chain fatty acids by perfused forearm muscles in vivo. Oral replacement therapy restored plasma carnitine levels to normal, but not liver or muscle carnitine levels, and was accompanied by clinical improvement.


Chronic pulmonary insufficiency of prematurity (CPIP). This report describes a syndrome of delayed respiratory distress occurring in premature infants usually under 1,250 gm at birth. Unlike hyaline membrane disease, this syndrome occurs after four to seven days in a previously healthy infant; also unlike hyaline membrane disease, it persists for two to four weeks. Chronic pulmonary insufficiency of prematurity (CPIP) carries a 10% to 20% mortality rate. The infants are frequently apneic, require supplemental oxygen, but lack the radiologic findings of hyaline membrane disease or bronchopulmonary dysplasia. When compared with nondistressed infants of similar birthweight, infants with CPIP demonstrate slowly progressive atelectasis, hypoxemia, and hypercapnia. Recovery is usually complete by 60 days of age. The importance of CPIP is that an awareness of its existence can eliminate a false sense of security, often communicated to anxious parents, during the four-to-seven-day grace period before its appearance is clinically obvious. The physiologic similarities between CPIP and hyaline membrane disease suggest that lack of surfactant may play a role in the pathogenesis of CPIP.


Studies on cor pulmonale in cystic fibrosis: I. Effects of diuresis. The effects of acute diuresis in patients with cor pulmonale secondary to cystic fibrosis were studied. Both hemodynamic parameters and arterial blood gas changes were investigated. The major effect noted was a significant reduction of systemic venous pressure. Pulmonary artery and pulmonary artery wedge pressure either remained constant or declined slightly. No consistent changes were noted in cardiac output or arterial blood gases. Acute diuresis of moderate degree appears to be a safe and effective manner in which to treat the systemic venous congestion of cor pulmonale in this situation.


The phospholipase activity of sheep pancreatic juice. Sheep pancreatic juice was found to contain at least two enzymes which hydrolysed biliary lecithin. One enzyme was heat and acid labile and hydrolysed the fatty acid from position 1 (phospholipase A1); the other was heat and acid stable hydrolysing the fatty acid at position 2 (phospholipase A2). Lysophospholipase activity was also present. The phospholipases were active at pH values greater than 4.2, and would therefore function in the acid conditions (pH 3-6) of the sheep small intestine. The activity of the pancreatic phospholipases, and A2 in particular, was dramatically stimulated by the presence of the secretions of Brunner's glands which could be important in accelerating the hydrolysis of biliary lecithin in the lumen of the intestine. Phospholipase A1 was sensitive to acid in the range pH 2.5-3.5 and could therefore be partially inactivated by abomasal digesta; but phospholipase A2 was resistent to acid treatment.


The value of total aortography in the diagnosis of Takayasu's arteritis. The arteriographic and clinical spectrum of Takayasu's arteritis in a series of 23 cases is reviewed. The incidence of the disease appears to be much higher than is generally suspected. Although it primarily afflicts young women, children are frequently affected. Two clinical stages of the disease are recognized: an early systemic and a late occlusive phase. The signs and symptoms of both stages are protean and variable. The pathological appearance varies with the activity and duration of the disease. Total aortography is of primary diagnostic importance in demonstrating the characteristic appearance of the diseased aorta.


Plasma testosterone and dihydrotestosterone in male rats during sexual maturation and following orchidectomy and experimental bilateral cryptorchidism. Plasma concentration of testosterone and dihydrotestosterone (17beta-hydroxy-5alpha-androstan-3-one) were measured at frequent intervals (daily between day 20 and 40) in intact male rats from early pre-pubertal stage to full maturity. Effect of orchidectomy and experimental bilateral cryptorchidism on these two blood-born compounds at different stages of sexual maturation was also studied. A distinct spurt in testosterone level was noted on day 26, and in 3 days a leval of 2600pg/ml was reached, which was about 90% of the highest peak value (2940 pg/ml) seen at day 70. In the same animals dihydrotestosterone spurt was noted at the same time, but the peak value (163 pg/ml) was reached later (day 33). Within 4 days after orchidectomy plasma testosterone level showed no significant change in 20-day old animals, but dropped to 15% of the intact value in 40-day old ones, while remaining at a steady level of about 23% in older animals. Plasma dihydrotestosterone was undetectable after orchidectomy at each stage of sexual maturation. With bilateral cryptorchid animals plasma testosterone was higher than seen in the intact 20-day old control, but remained similar at other stages of sexual maturation. Plasma dihydrotesterone in the same animals was significantly less (p less 0.01) than those seen in the intact controls at all stages of sexual development except in 20-day old ones, where it was essentially similar.


Solubility fo fibrin clots in monochloroacetic acid. A reflection of serum pepsinogen levels. Fibrin clots formed from normal plasma dissolve readily in 1% monochloroacetic acid at 37 C. However, if the clots are washed thoroughly before the acid is added, they are no longer soluble. The agent present in the serum which causes dissolution of the fibrin clot was isolated and identified as pepsinogen. Because of the low pH of monochloroacetic acid the pepsinogen is activated and the clots are digested, simulating the dispersion of a fibrin clot which occurs in the absence of fibrin-stabilizing factor (factor XIII). Because of its higher pH, urea will not activate pepsinogen and is therefore a better agent to screen factor XIII deficiencies.


Perceived life-stress and psychopathology among mothers of young children. Mentally ill mothers of young children, contrasted with well mothers, reported greater stress in their own lives, and in those of their husbands and parental families. Within each group of mothers, there was a different relationship between life-stress and psychological symptoms. Within the mentally ill group, stress was associated with both diagnosis and chronicity.


Elevated blood serotonin concentrations in unmediated chronic schizophrenic patients: a preliminary study. The authors found higher serotonin concentrations in the blood of unmedicated chronic schizophrenic patients than in the blood of medicated schizophrenic patients or normal control subjects. This finding is consistent with the previous observation that the level of monoamine oxidase activity is low in the platelets of chronic schizophrenics.


Ecology of California encephalitis viruses on the Del Mar Va Peninsula. I. Virus isolations from mosquitoes. The ecology of California encephalitis viruses was studied on the Del Mar Va Peninsula. Adult mosquitoes were collected weekly from May to October of 1971 and monthly from May to October of 1972, using CDC miniature light traps with Dry Ice. Floodwater mosquitoes were assayed for virus in suckling mice or cell cultures. In 1971 over 77,000 mosquitoes were processed, resulting in 33 virus isolations. In 1972, over 106,000 were processed and 63 virus strains were recovered. Of the 1971 strains, all but one were recovered from Aedes atlanticus mosquitoes, and of the 1972 strains all but two were recovered from A. atlanticus. All A. atlanticus strains were neutralized by Keystone virus mouse hyperimmune ascitic fluid (MHAF). All other strains were recovered from A. canadensis mosquitoes. The single 1971 strain, and one strain from 1972, were neutralized by Jamestown Canyon MHAF. The remaining strain was neutralized by Keystone MHAF. The rate of virus recovery from A. atlanticus remained approximately the same, both between years and during each year studied, even during periods when large numbers of adults were emerging, suggesting that these mosquitoes had emerged infected.


Bertioga (Guama group) and Anhembi (Bunyamwera group), two new arboviruses isolated in São Paulo, Brazil. Bertioga and Anhembi are two newly recognized arboviruses that were isolated in Saõ Paulo, Brazil. Bertioga was isolated from sentinel mice exposed in a forest of that name, and was shown to belong serologically to the Guama group of arboviruses. Anhembi, the second virus described, was isolated from pools of mosquitoes (Phoniomyia pilicauda and trichoprosopon pallidiventer), and from a spiny rat (Proechimys iheringi), and was shown to be a new member of the Bunyamwera group. The viruses are sensitive to sodium desoxycholate and are filterable through a millipore membrane of 450 mum pore size. Both are pathogenic for suckling mice and grow well in Vero cells, producing clear cytopathic effects. Detailed antigenic comparisons of Anhembi virus with other members of the Bunyamwera group isolated in the Americas, and of Bertioga virus with the members of the Guama group are presented. Both are believed to be new arboviruses in their groups.


Physiocochemical properties of a lipoprotein antigen of Echinococcus granulosus. Molecular weight and optical properties of the lipoprotein B, the main antigen produced by the parasite in sheep hydatid fluid, have been determined. By sedimentation equilibrium studies, its molecular weight has been found equal to 120,000. Circular dichroism and optical rotatory dispersion spectra are consistent with an alpha-helix content of about 50%, and this ordered structure is not completely destroyed by dissociation in guanidinium choloride. The ORD spectrum is discussed in relation to the biological function of the lipoprotein antigen.


Hemodynamic responses to mechanical ventilation with PEEP: the effect of hypervolemia. The hemodynamic effects of prolonged mechanical ventilation with positive end-expiratory pressure (PEEP), with and without blood volume augmentation, were studied in 18 beagles anesthetized with halothane (0.7 per cent end-tidal). Addition of 12 cm H2O PEEP during mechanical ventilation in normavolemic dogs was associated with reductions of transmural cardiac filling pressures, cardiac index and stroke index to 50 per cent of control values. Circulatory adaptation did not occur. Filling pressures and flow remained unchanged during the ensuing 8 hours when PEEP was maintained. They returned to control levels when PEEP was discontinued, except for the transmural right ventricular end-diastolic pressure, which remained elevated above control levels. Systemic vascular resistance was unchanged, but pulmonary vascular resistance doubled upon addition of PEEP. Following autologous whole blood transfusion (25 ml/kg) during mechanical ventilation with PEEP, cardiac index returned to, and remained at, control levels. After PEEP was discontinued, cardiac index increased acutely and remained elevated for the remainder of the study period (as long as 7 hours). Comparable transfusion during mechanical ventilation without PEEP elevated cardiac index only transiently. Right atrial, pulmonary capillary wedge, and right and left ventricular end-diastolic pressures showed marked increases relative to atmospheric with PEEP and after transfusion. Calculated transmural pressures demonstrated clear reductions with application of PEEP, followed by increases to control levels with transfusion and further increases to above control when PEEP was discontinued. Study of ventricular function curves revealed that changes in filling pressures and not to changes in ventricular contractility. Transmural pulmonary arterial diastolic pressure rose throughout the 12 hours of study, despite return of pulmonary vascular resistance to control level with removal of PEEP. Thus, acute decreases in cardiac filling pressure, cardiac index, and stroke index persist consequent to application of PEEP, and circulatory adaptation does not occur. The apparent hemodynamic deterioration may be reversed by blood volume augmentation, but when PEEP is discontinued, hypervolemia with consequent increases in filling pressures and a move along a ventricular function curve will occur. Changes in cardiac index will depend upon the overall state of right and left ventricular contractility.