Fructose metabolism in plants. Isolation and properties of pea seed frucktokinase. Fructokinase from pea (Pisum sativum L.) seed has purified 100-fold. The enzyme required reduced sulfhydryl groups for activity. It also exhibits an absolute requirement for potassium ions (Km = 3 mM) and is unstable when not stored with a high concentration of potassium ions. The isoelectric point of the enzyme is 4.7 and it has a molecular weight of 44 000 +/- 700 daltons as determined  by molecular sieve chromatography and sedimentation velocity techniques. A Hill plot of the potassium ion data suggests that two potassium sites are present on the enzyme. The MgATP saturation curve was non-Michaelis-Menten with a slight positive cooperativity. Pea seed fructokinase is highly specific for fructose and ATP. A comparison of pea seed fructokinase properties and those of liver and bacterial origin is presented.


Polymeric structure of a cyclic adenosine 3', 5',-monophosphate dependent protein kinase from the dimorphic fungus Mucor rouXII. Adenosine 3', 5'-monophosphate (cAMP) dependent protein kinase from yeast cells of Mucor rouxii was partially purified and examined by sedimentation in sucrose density gradients. In the presence of histone and cAMP this procedure allowed the separation of the catalytic moiety from the cAMP binding activity, indicating that the enzyme had dissociated into subunits. The dissociation was accompanied by conversion of the enzyme activity from a cAMP dependent to a cAMP independent form.


Specific binding of human and bovine growth hormones to hypophysectomized rat hepatocytes. Specific binding of 125I-HGH and 125I-bGH was obtained in hypophysectomized rat liver cells. Two types of somatogenic receptors were found with apparent dissociation constants of 4.2 x 10(8) M-1 and 1.7 x 10(7) M-1. The number of sites for the higher and lower affinity receptors were: 1 x 10(4) and 6 x 10(3), respectively. Human, bovine and equine growth hormones appear to bind to liver cells with equal affinity, while ovine prolactin needs at least a two-order-magnitude greater concentration to displace 125I-bGH. A parallelism between biological activity and binding data was observed.


Characteristics of reinnervation of skeletal muscle in the rat. Both extra and intracellular fibrillation activity recorded in vivo was studied during nerve-muscle reinnervation, in control rats and in rats treated with actinomycin D. The study was performed at different times after nerve crushing. End-plate potentials (EPP's) and muscle action potentials were always present on the eleventh day after denervation. Fibrillation activity recorded extracellularly began to decrease on the twelfth day. Intracellular fibrillation activity was found in single muscle cells simultaneously with evoked EPP's muscle action potentials. In early stages of reinnervation two EPP's were recorded in a single muscle cell, thus indicating double innervation. When presynaptic action of actinomycin D was tested no changes were found in miniature end-plate potential frequency. Muscles from rats submitted to early treatment with actinomycin D did not show any delay in the onset of reinnervation. In muscles from rats submitted to late treatment, extrasynaptic sensitivity to acetylcholine was ascertained regardless of the presence of functional reinnervation. Chronic stimulation of denervated muscles, while suppressing fibrillation activity, did not interfere with reinnervation. The results reported suggest that reinnervation can take place independently of fibrillation activity as well as of extrasynaptic receptors.


Response of the atrial pacemaker to dobutamine. The action of dobutamine, (+/-)-4- [2- [[3-(p-hydroxyphenyl)-1-methylpropyl]amino]ethyl] pyrocatechol hydrochloride was studied on the pacemaker of the isolated rat atria. The dose-chronotropic response curve showed a typical bell-dome shape of the sympathomimetic amines. Reserpinization of the animals did not change the curve of the agonist. Cocaine (6.7 microgram/ml) induced a decrease of the sensitivity of the rat atria pacemaker for dobutamine (p less than 0.001). Propranolol (3 X 10(-8) and 10(-7) M) provoked a shift to the right of the dose-response curve for dobutamine. Also, the last concentration of the antagonist depressed the maxima (p less than 0.01). Phentolamine failed to prove a possible alpha-adrenergic action of the drug on the pacemaker. The response to dobutamine was not affected when monoaminoxidase was inhibited by pretreatment with pargyline, or when catechol-O-methyltransferase was inhibited by exposure to U-0521 (3,4 dihydroxy-alpha-methylpropiophenone). These results indicate that dobutamine: a) is a beta-adrenergic agent, b) is not a good substrate of MAO, c) is a direct-acting sympathomimetic amine.


Serum triglycerides and cholesterol and serum high-density lipoprotein cholesterol in highly physically active men. The influence of extensive physical activity upon plasma lipids, in particular HDL cholesterol, was investigated. The material consisted of 23 regularly training men (mean age 44 years, average exercise 83 km running or skiing weekly), 15 healthy men (mean age 47 years), 10 young men (mean age 22 years), 12 healthy women (mean age 32 years) and 18 hyperlipidaemic patients. The exercise increased serum HDL cholesterol and FFA concentrations and decreased triglyceride levels significantly, but had no significant effect upon serum cholesterol concentration. There was a positive correlation between the amount of weekly exercise in km and plasma HDL cholesterol concentration. Exercising more than 70 km/week increased plasma HDL concentration clearly above the normal level. The advantages of an increase in plasma HDL cholesterol are discussed.


Glucagon effects on plasma cyclic AMP and other reactants in normals and low insulin responders. The metabolic response to i.v. glucagon was evaluated in 11 normal individuals and 8 healthy low insulin responders. Elevations of plasma cyclic AMP and blood glucose were similar in both groups. Accordingly, no indications were seen of differing hepatic responsiveness to glucagon. In contrast, the groups differed in the course of plasma glycerol during the test.


A proposed bioanthropological approach linking ritual and opiate addiction. This paper presents preliminary conjectures about possible neurobiological relationships among seemingly disparate phenomena: religious rituals, native curing therapies, and the pharmacodynamic, psychological, and sociocultural components of opiate addiction. Central to the discussion is an analysis of the function of opiate receptors, the endogenous neurochemical that binds to opiate receptors, and the impact of exogenous opiates on human behavior. Throughout the paper a synthetic but admittedly speculative approach is employed.


The localization of a histamine H2-receptor adenylate cyclase system in canine parietal cells and its inhibition by prostaglandins. A method is described for the preparation of parietal cell-enriched suspensions from dog gastric mucosa. Histamine and E type prostaglandins produce an elevation of cyclic AMP concentration in mixed cell preparations. Parietal cell-rich fractions respond to histamine but only weakly to prostaglandins whilst in fractions virtually free from parietal cells the converse is observed. Prostaglandins which are good antisecretory agents, PGE1, PGE2 and 16,16 dimethyl PGE2 are potent inhibitors of the histamine elevations of cyclic AMP in parietal cell-rich fractions, whilst PFG2alpha shows 1% of their potency. The experiments described support the view that histamine stimulates gastric acid secretion by excitation of an H2-receptor adenylate cyclase system in the plasma membrane of the parietal cell and that acid secretory inhibition by prostaglandins is a result of inhibition of that system.


Radiologic assessment of pituitary microadenomas. Radiographs of 146 patients who had a pituitary adenoma removed by the transsphenoidal approach were reviewed. The area and volume of the sella were measured in all the patients. In 73 patients the sella had a normal size and appearance as shown on routine lateral and frontal radiographs. However, thin-section tomograms of the sella in these patients demonstrated findings indicative of an intrasellar mass in all but three instances. The diagnosis of pituitary microadenoma (adenoma less than 1.5 cm in diameter) may, therefore, be missed if only plain skull radiographs are used to assess the sella. No correlation could be shown between the location of the sellar changes seen using thin-section tomography and the histologic type of pituitary adenoma.


interactions of ionizing radiation, nitrosamines, sulfonoxyalkanes and antioxidants as they affect carcinogenesis and survival in mice. Butylated hydroxytoluene (BHT), pretreatment of 8-wk-old BALB/c mice for 28 days protected against 30-day lethality by X-rays, diethylnitrosamine (DEN), dimethylnitrosamine (DMN) and ethyl methanesulfonate (EMS) but not against methyl methanesulfonate (MMS). In X-ray survivors, neither mean survival nor leukemia incidences were affected by BHT. However, BHT (lifetime), given alone or with DEN (300 MG/KG BW in H2O) or 250 R X-rays, increased irradiated survivors at 18 months but not leukemia or tumor incidences. BHT + DEN treated females had increased survival and a decreased frequency of forestomach squamous carcinomas compared with DEN alone; no differences were seen in males or in pulmonary adenomas. In X-ray + DEN treated females, effect upon survival was additive, but the specific diseases causing this effect were not identified.


Tolyl-specific IgE antibodies in workders with hypersensitivity to toluene diisocyanate. Incorporation of a p-tolyl (mono) isocyanate-human serum albumin (TMI-HSA) antigen conjugate into a solid phase radioimmunoassay permitted detection of tolyl-specific IgE antibodies in 3 of 4 workers with clinical hypersensitivity to toluene diisocyanate (TDI). By comparison 19 TDI-exposed, non-sensitized workers had antibody titers similar to those found in normal adults. High titers of tolyl-specific IgE antibodies were not correlated with high levels of total serum IgE. Use of the monofunctional isocyanate in place of TDI in antigen preparation prevented cross-linking of antigen protein, an effect usually associated with TDI, and also assured that tolyl groups were sterically exposed. TMI-HSA antigens may prove beneficial in serological or cutaneous evaluation of TDI-sensitized workers.


Prevalence of right ventricular involvement in inferior wall infarction assessed with myocardial imaging with thallium-201 and technetium-99m pyrophosphate. To assess the prevalence and clinical relevance of right ventricular involvement in acute inferior wall infarction, 78 consecutive patients with the latter condition were studied with thallium-201 and technethium-99m pyrophosphate myocardial imaging. Right ventricular involvement was determined from superimposition of the 45 degree left anterior oblique thallium-201 and technetium-99m pyrophosphate images. All 78 patients shoed thallium-201 defects. Sixty-four patients had positive pyrophosphate scans, and 24 of these (37.5 percent) showed right ventricular involvement. None of the patients with right ventricular involvement in this consecutive series showed the classic signs of severe right ventricular failure, although subclinicalright ventricular dysfunction may have been present. There was no significant difference in the incidence of cardiogenic shock between the groups with and without right ventricular involvement. It is concluded that right ventricular involvement in acute inferior wall infarction is relatively frequent but not necessarily associated with severe right-sided pump failure. In patients with acute inferior wall infarction and severe pump failure, dual imaging provides a simple nonivasive method of identifying the subgroup of patients with right ventricular involvement who may benefit from volume loading.


Long-term effectiveness of dietary iron and ascorbic acid in the prevention and cure of cadmium toxicity in rats. The protective and curative effects of dietary iron and ascorbic acid on chronic (180 days) cadmium toxicity in rats were examined. Growth retardation and anemia were observed in rats fed a diet containing 50 ppm of cadmium for 180 days; during this period the contents of iron in the liver, kidney, spleen, testis, intestine, and tibia decreased and the zinc contents of the liver and kidney increased, but the calcium content of bone did not change. Addition of 400 ppm of iron and 1% of ascorbic acid to the cadmium-containing diet overcame the growth retardation and anemia due to cadmium toxicity and reduced the tissue levels of cadmium; however, it did not restore the zinc contents in the liver, kidney, and bone to normal. Similar effects were observed when these compounds were added to cadmium containing diet for 90 days after feeding the cadmium diet alone for 90 days. The glutamic-pyruvic transminase and glutamic-oxaloacetic transminase activities in the plasma of rats fed the cadmium diet increased significantly and these increases were prevented by supplementing the diet with iron and ascorbic acid. Glucose, urea, and alkaline phosphatase in the plasma and glycogen in the liver were not changed by feeding the cadmium diet for 180 days. These results indicate the long-term effectiveness of supplementing the diet with iron and ascorbic-acid for preventing and curing dietary cadmium toxicity in rats.


Increased histidine and histamine content in the brain of chronic uremic rats. Cause of enhanced cerebral cyclic adenosine monophosphate in uremia? In rats with experimental chronic renal insufficiency (90% nephrectomy) the histidine content in brain was increased (+ 35%) in spite of normal plasma values and decreased concentrations in the striated muscle (-23%). The finding of a raised histidine level in the brain seems to be a uremia specific disorder, probably cuased by a local disturbance in histidine metabolism. In addition an increase of the histidine decarboxylation product histamine could be observed in the brain of rats with chronic renal insufficiency, as compared to pair-fed controls. This increase was directly related to the severity of azotemia. In the pathogenesis of the histamine alteration the increased histidine content in the brain of uremic rats must be considered, since the specific histidine decarboxylase is not saturated by the normal endogenous level of the amino acid precursor. Probably the increased histamine contributes to the raised cerebral cyclic AMP in the brain of uremic rats.


Overview and horizons in prevention of some human infectious diseases by vaccination. The present measles problem in the United States, an estimated 918,500 cases in 1977, is attributed to the failure of the 14-year vaccination program to immunize enough children to prevent continued circulation of the virus and recurrent outbreaks. A new strategy for rapidly overcoming this problem is recommended. There appears to be no current congenital rubella syndrome problem against which the rubella vaccination program in the United States is directed. However, the continued annual infection of an estimated two million children conceivably could again bring fourth a rubella virus with a greater capacity for producing congenital rubella syndrome, and a modification of the present program is recommended. About 80 to 90% of the annual 60-70 million cases of severe enough to confine the victim to bed influenza are not caused by the influenza viruses. Except for the few thousand additional deaths directly attributed to influenza A virus during the epidemic years, mortality rates for pneumonia, heart diseases, chronic bronchopulmonary diseases, and other former "high-risk" conditions have continued to decrease in recent years, and have not risen during the 12-month periods of epidemic years. A re-evaluation of the current influenza vaccination policy is recommended. Prospects for hepatitis B and varicella-zoster vaccines are discussed.


Varicella-zoster virus. Prospects for active immunization. A live attenuated varicella-zoster (V-Z) virus vaccine has been developed and tested by Dr. M. Takahashi and his colleagues in Japan. This vaccine appears to prevent varicella and is associated with minimal side effects even in patients at high risk to develop severe varicella. Antibody to V-Z virus appears after V-Z vaccination. This antibody has been detected by a variety of serologic technics, and it has been demonstrated to persist for as long as two years after vaccination. Thus far, V-Z vaccine has not been associated with subsequent zoster, but long-term studies will be required before this possibility can be ruled out.


Kleine-Levin syndrome associated with fire setting. Kleine-Levin syndrome is characterized by periodic hypersomnia associated with megaphagia and striking behavioral and psychiatric symptoms; it occurs primarily in adolescent boys. We treated a 17-year-old boy who had typical recurring somnolent episodes. His bizarre behavior included fire setting and stealing, both of which may have represented compulsions. His EEG during a sleepy episode was diffusely abnormal with generalized slowing of background activity; as he awoke and improved clinically, his EEG returned to normal. Between episodes, his EEG was normal. The relationship between Kleine-Levin syndrome and other sleep disorders is discussed. The neurochemistry and neurocircuitry that may provide the requisite substrate for this complex and fascinating neuropsychiatric disorder are briefly reviewed.


Comparison of human rotavirus disease in tropical and temperate settings. Human rotaviruses (HRV) are a common cause of acute nonbacterial gastroenteritis in pediatric patients. A prospective study of HRV disease in a temperate (Dallas) and a tropical (San Jose, Costa Rica) setting demonstrated differences in seasonal distribution. In both locales, HRV accounted for 50% to 60% of acute nonbacterial gastroenteritis episodes from December through February; this period corresponded to the cooler months of winter in Dallas and to the dry season in San Jose. During the rest of the observation year, the virus was not recovered from any Dallas patients, but was found in 30% to 40% of Costa Rican patients in every month but May. Signs, symptoms, and laboratory values suggest the small bowel as the major site of pathophysiology; mucosal disruption may occur in some cases.


Obstructive jaundice caused by hepatocellular carcinoma. Report of three cases. A cholestatic syndrome secondary to extrahepatic biliary obstruction as the presenting manifestation of hepatocellular carcinoma is described in three cases. The mechanism is related to the invasion of intrahepatic bile ducts by the carcinoma. The consequent mechanical obstruction is due to either a continuous distally growing tumor cast of the biliary tree, distal migration of a necrotic tumor fragment, or hemobilia. In the cirrhotic patient with a predisposition for the development of liver cancer, the physician should be aware of the presentation with obstructive jaundice as a mechanical complication of hepatocellular carcinoma.


Calcified mucinous adenocarcinoma of the stomach. Two cases of unusual mucinous adenocarcinomas of the stomach with calcification are reported. One of the cases demonstrated hypercalcemia. Endoscopic verification of the calcifications was confirmed. This report represents the 49th and 50th reported cases in the world's literature.


Clustering of different subtypes of hepatitis B surface antigen in families of patients with chronic liver diseases. Clustering of hepatitis B surface antigen (HBsAg) with both subtypes adr and adw in three families of patients with chronic liver diseases or hepatocellular carcinoma was demonstrated in Taiwan where adw is the main subtype. The subtype in the children was similar to that in their mothers, suggesting maternal transmission. In all the family units clustered with different subtypes, the same pattern occurred, invariably with fathers carrying HBsAg/adr and the children carrying HBsAg/adw. The subtype difference clearly rules out the transmission of hepatitis B virus (HBV) from father. Horizontal infection with the locally dominant adw-subtyped HBV in the children of fathers carrying HBsAg/adr explains the discrepancy of the subtypes in these families. Clustering of two HBsAg-positive brothers with hepatocellular carcinoma in one of the families was found. That both adr-subtyped and adw-subtyped HBV are capable of inducing chronic active hepatitis in another family suggests that host factors are probably more important in determining the clinical course of HBV infection.


Travelers' diarrhea among United States Marines in South Korea. A battalion of United States Marines traveling to South Korea in the spring of 1976 was studied to determine the incidence and etiology of gastroenteritis. During the three weeks they visited South Korea, 21% of 694 marines developed diarrhea. Stool and serum specimens collected before, during, and after their stay were examined for evidence of infection with Salmonella, Shigella, and Vibrio species, enterotoxigenic and invasive Escherichia coli, reovirus-like agent (RVLA), and intestinal ova and parasites. Infections with these agents were uncommon; 91% of 44 closely studied cases of gastorenteritis were unexplained. Five per cent of 169 marines had serologic evidence of recent infection with RVLA, and 3% of 273 marines had serologic evidence of infection with heat-labile enterotoxin producing E. coli over an eight-week period. However, infections with these agents were not associated with most cases of diarrhea in South Korea. It is concluded that infectious agents previously thought responsible for travelers' diarrhea were not responsible for gastroenteritis among United States Marines arriving in a temperate climate.


Effect of cyclic nucleotides on mitogen. Responsiveness of lymphocytes from patients undergoing dialysis. Lymphocytes from 10 asymptomatic patients undergoing hemodialysis and from eight control subjects were repeatedly cultured with exposure to various concentrations of cyclic nucleotides and theophylline in addition to mitogen. The blastogenic response of the patients' lymphocytes was inhibited by molar concentrations of dibutyryl cyclic AMP which had much less or no inhibitory effected on the response of the control subjects' lymphocytes. This suppressive effect was not potentiated by theophylline. Cyclic GMP enhanced the proliferative response of the patients' lymphocytes as well as that of the controls. In contrast to absolute counts per minute per culture, the suppression by dibutyryl cyclic AMP of mitogen-induced blastogenesis noted in this study clearly separated the in vitro behavior of the patients' lymphocytes from  that of the controls' lymphocytes and may serve as a useful marker of cellular dysfunction in such patients.


Continuous flow plasma exchange in the treatment of homozygous familial hypercholesterolemia. We report the clinical and laboratory effects of continuous-flow plasma exchange in two patients suffering from homozygous familial hypercholesterolemia. In one (Case 1) plasmapheresis was performed at fortnightly intervals over a period of 18 months; in the other (Case 2) the necessity for surgical relief of an associated supravalvular aortic stenosis resulted in premature termination of the trial. The plasma cholesterol levels in both patients fell by 35 per cent from the mean before study in the course of treatment. In Case 1 this was associated with marked regression of the patient's xanthomas, disappearance of the S-T segment depression seen on effort electrocardiograms obtained prior to the introduction of plasmapheresis, possible widening of the stenosis present at the origin of the left anterior descending coronary artery, and a marked increase in exercise tolerance and diminished frequency of anginal attacks. Cessation of cholestyramine and clofibrate administration during this study did not in any way reverse the reduction of plasma cholesterol achieved by means of plasmapheresis combined with drug therapy. We conclude that plasmapheresis has a role to play in the management of patients with homozygous familial hypercholesterolemia.


Ectopic secretion of chorionic gonadotropin by a lung carcinoma. Pituitary gonadotropin and subunit secretion and prolonged chemotherapeutic remission. The ability of tumor markers to improve cancer therapy is not established. We studied a man with a human chorionic gonadotropin (HCG)-secreting large cell carcinoma of the lung and gynecomastia. Preoperatively, levels of HCG (109 ng/ml), its alpha and beta subunits (3.2 and 21 ng/ml, respectively) and plasma estradiol were elevated. Despite apparently complete tumor resection and total resolution of gynecomastia, HCG titers remained elevated (3.3 ng/ml), heralding tumor recurrence three weeks later. Because the pathophysiologic consequences of the ectopic secretion of HCG on pituitary function are not established, we administered 100 microgram of gonadotropin-releasing hormone (LHRH) and observed a markedly delayed increase in pituitary gonadotropins. Early chemotherapy, guided by persistence of HCG, reduced HCG to undetectable levels, restored to normal the response to LHRH and resulted in a distinctly unusual 30-month complete remission. Use of HCG as a tumor marker levels is more sensitive than the symptom of gynecomastia and may permit detection of small, potentially curable tumor foci.


Gonadotropin receptors of human corpus luteum during menstrual cycle and pregnancy. Specific high-affinity low-capacity binding of human chorionic gonadotropin (hCG) and lutropin (hLH) was demonstrated in the plasma membrane fractions of human corpora lutea. The number of binding sites for both hormones increased from early to late luteal phase, whereas regressing corpus luteum from proliferative phase did not bind either hormone. On the basis of apparent dissociation constants the affinity of the receptor for hLH is highest during early luteal phase and decreases toward the end of the cycle, which may reflect an increasing insensitivity of the corpus luteum to circulating hLH. By contrast, the affinity of the receptor for hCG is highest in the midluteal phase. There are gonadotropin binding sites in the human corpus luteum also during pregnancy, but they are saturated by endogenous hCG. Evidence for this was obtained by elution of hCG with 0.15M sodium chloride at pH 2.3 from washed plasma membrane fractions of luteal tissue from six to 16 week's gestation. After acid treatment and neutralization these preparations showed specific binding for 125I-labeled hCG, but not for 125I-labeled hLH. Our results demonstrate a shift in the balance of affinity of the gonadotropin receptor from hLH to hCG during the course of luteal phase, and during pregnancy the binding sites appear to be available for hCG only.


Effect of immunization on the development of latent ganglionic infection in mice challenged intravaginally with herpes simplex virus types 1 and 2. Immunization of BALB/c mice with virulent and avirulent strains of HSV-1 resulted in high levels of neutralizing antibody and protected against both the lethal effect of the virus and the development of a latent ganglionic infection when animals were challenged by the intravaginal route. In animals immunized with avirulent strain of HSV-2 and challenged with a high virulent strain of HSV-2, substantial protection against death was observed despite low levels of neutralizing antibody. Nineteen per cent of the survivors, however, developed a latent ganglionic infection. Relatively little protection was observed in mice immunized with HSV-1 and challenged with HSV-2.


Hepatitis A and B: serologic survey of various population groups. Seven population groups were tested by radioimmunoassay for the presence of hepatitis A antibody (anti-HAV), hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs). Detection of anti-HAV was indicative of past hepatitis A infection and presence of HBsAg or anti-HBs indicated past hepatitis B infection. The results of tests of 680 serum specimens from the seven groups were as follows: (1) of 100 newly admitted children to Willowbrook where hepatitis A and B were hyperendemic, 32% had anti-HAV and 4% had anti-HAV and 4% had HBsAg (1%) plus anti-HBs (3%); (2) of 100 Willowbrook residents who lived in the institution about three or more years, 97% had anti-HAV and 90% had HBsAg (32%) plus anti-HBs (58%); (3) of 100 new Willowbrook employees, 50% had anti-HAV and 13% had anti-HBs; (4) of 100 Willowbrook employees who worked in the institution more than three years, 75% had anti-HAV and 30% had HBsAg (3%) plus anti-HBs (27%); (5) of 80 house staff physicians, 27.5% had anti-HAV and 10% had anti-HBs; (6) of 100 student 34% had anti-HAV and 6% had anti-HBs; and (7) of 100 suburban teenagers 4% had anti-HAV and 5% had anti-HBs. This study confirmed the variability of the prevalence of hepatitis A and B markers among different population groups and the effect of socioeconomic status and environmental factors on the incidence of past infection caused by hepatitis A and B viruses.


Acute asthma. Part II. The effects of therapy on heart rate and blood pressure. This study evaluated cardiovascular effects of epinephrine in the treatment of asthma. Heart rates, systolic and diastolic blood pressures were monitored in 64 patients treated for acute asthma. Treatment regimens included subcutaneous epinephrine in doses of 0.1 to 0.5 mg. Pretreatment heart rates ranged from 64 to 136 beats per minute and systolic and diastolic blood pressures from 80 to 190 and 50 to 108 mm Hg respectively. Epinephrine in all doses and repeated as often as three times did not raise blood pressure or heart rates, and in the highest dose or in patients with pressures in the hypertensive range exerted a hypotensive effect. Adverse cardiovascular effects of epinephrine observed in normal subjects are significantly modified in acute asthma and its use should be considered in light of these findings.


The treatment of herpetic reinfection with levamisole. The effect of levamisole on both clinical disease and virus recovery was studied in rabbits that were first infected with herpes simplex virus in one eye and then reinfected 14 days later by inoculation of the second eye. Reinfected rabbits treated with levamisole before reinfection developed significantly milder and smaller lesions than untreated controls. Virus recovery from the corneas was also less in the levamisole-treated animals than in the untreated controls.


Mechanisms of platelet adhesion to the basal lamina. The human glomerular basal lamina (HGBL) is composed of collagenous and noncollagenous glycoproteins. We assessed the role played by each costituent in platelet-basal-lamina interaction by selective cleavage and removal of each component by clostridial collagenase or by pepsin. When noncollagenous proteins are removed from HGBL, human platelets exhibit littel reactivity toward the residual collagen framework of the isolated basal lamina. With the noncollagen matrix of basal lamina, after removal of the bulk of the collagen, platelet adhesion and spreading proceed normally in the presence of divalent cations, similar to what occurs on intact basal lamina. No platelet degranulation or aggregation is observed. The results indicate that the basal lamina collagen, even in its native packing arrangement, lacks affinity for platelet adhesion and is incapable of triggering platelet release reactions. Platelet adhesion and spreading on the basal lamina appears to depend primarily on the presence of the noncollagen components and to require divalent cations. The data suggest the presence on platelets of receptors for basal lamina distinct from those for interstitial collagens. These receptors activate a unique modulation of platelet behavior, ie, adhesion and spreading without degranulation. A difference in biologic function of the basal lamina and interstitial collagens is apparent in these experiments.


Actions of peptides isolated from amphibian skin on pancreatic acinar cells. In dispersed acinar cells prepared from guinea pig pancreas, peptides isolated from amphibian skin (caerulein, bombesin, litorin, and physalaemin) as well as eledoisin, a peptide isolated from the posterior salivary gland of a Mediterranean octopod, increased outflux of 45Ca, release of bound 45Ca, accumulation of cyclic GMP, and release of amylase. In addition, bombesin, litorin, physalaemin, and eledoisin each increased the initial uptake of 45Ca by dispersed acinar cells, whereas C-terminal octapeptide of porcine cholecystokinin (CCK-OP) and carbamylcholine did not increase the initial uptake of 45Ca but, rather, abolished the increase caused by the other agents. None of the actions of these amphibian peptides was altered by concentrations of atropine sufficient to abolish the effects of muscarinic cholinergic agents. None of the amphibian peptides altered cellular cyclic AMP or the increase caused by secretin or porcine vasoactive intestinal peptide (VIP). Acinar cells preincubated with 45Ca plus bombesin showed the same rate of release of 45Ca as did control cells and this rate was not altered by adding bombesin but was increased fivefold by adding CCK-OP. In terms of their chemical structures as well as the potency and efficacy with which they alter acinar cell function, the amphibian peptides plus CCK-OP can be grouped into three pairs: caerulein with CCK-OP, bombesin with litorin, and physalaemin with eledoisin.


Action of PMSG and asialo-PMSG on rat Leydig and granulosa cells. Highly purified pregnant mares serum gonadotropin (PMSG) was nearly as potent as ovine luteinizing hormone (LH) and human follicle stimulating hormone (hFSH) when bioassayed in vitro in systems known to respond primarily to LH or FSH. An analogue of human chorionic gonadotropin treated with neuraminidase, galactosidase, beta-N-acetylglucosaminidase, and mannosidase (hCG) inhibited the stimulatory effects of hCG, LH, and PMGS on cAMP accumulation in rat Leydig cells but did not inhibit the stimulatory effects of FSH or PMSG on cAMP accumulation in ovarian granulosa cells obtained from immature rats fed diethylstillbestrol. Thus PMSG appeared to form functional complexes with both LH and FSH receptors and may be unique among mammalian gonadotropins. Treatment of PMGS with neuraminidase increased its potency nearly tenfold in vitro apparently by increasing its affinity for both LH and FSH receptors. Although the kinetics of PMSG binding were not investigated with radiolabeled materials, indirect functional binding studies are described that suggest that hCG more rapidly forms stable hormone-receptor complexes than PMSG, asialo-PMSG, FSH, and LH when all hormones are incubated under the same conditions.


GnRH membrane binding: identification, specificity, and quantification in nonpituitary tissues. Utilizing biologically active 125I-labeled gonadotropin-releasing hormone (125I-GnRH), specific binding with two affinites [KA (high) = 3.2 x 10(8) M-1, KA (low) = 10(5) M-1] were identified in membrane preparations derived from the 10,800 x g pellet of rat pituitary. GnRH-specific low affinity sites (KA - 10(5) M-1) were identified in liver, spleen, renal cortex, lung, testis, ovary, and cardiac muscle. Hypothalamic tissue demonstrated both high- and low-affinity binding. When 125I-GnRH was bound and dissociated, the labeled GnRH retained fully ability to rebind to fresh membrane preparations. That is, binding was not associated with loss of biological activity of GnRH. However, when unbound 125I-GnRH was exposed to the membrane fraction of liver, almost all receptor binding activity disappeared. The presence of low-affinity binding sites in peripheral tissues raises several possibilities: 1) they act as a simple reservoir mediating metabolic clearance of GnRH; 2) they represent enzyme binding sites involved in degradation of GnRH; 3) they mediate peripheral actions of GnRH; or 4) they are simply a cellular membrane constituent unrelated to target actions of GnRH.


Adrenergic vasoconstriction of the goat middle cerebral artery. The effects of field electrical stimulation on the contractile response of the isolated middle cerebral artery of the goat were evaluated before and after the use of experimental procedures designed to test the adrenergic component involved. Supramaximal stimuli produced frequency-dependent increases in tension. This response was significantly reduced by phentolamine (10(-6) M), tetrodotoxin (3 X 10(-6) M), and bretylium (5 X 10(-5) M), but not by cocaine (10(-6) M). Arterial segments from goats pretreated with reserpine and from goats in which both superior cervical sympathetic ganglia had been removed 12 days prior to the experiment also showed a significant decrease in the contraction elicited by electrical stimulation. The norepinephrine concentration of the arteries of the circle of Willis from control goats was 2.10 microgram per gram of tissue. Reserpine or gangliectomy reduced the catecholamine content to undetectable levels. It is likely that a major part of the contractile response of cerebral arteries to electrical stimulation is due to release of endogenous norepinephrine which in turn activates the alpha-adrenergic receptors.


Effects of prostaglandin E2, analogs, fatty acids, and indomethacin on fibrinogen level. Dose-response relations in rabbits for 3-h intravenous infusion of prostaglandin E2 (PGE2) and (15S)-15-methyl-1-prostaglandin E2 methyl ester (MePGE2) on plasma fibrinogen and systolic blood pressure were determined and described by regression equations. MePGE2 was 20 times more active than PGE2. Fibrinogen synthetic rate responses to PGE2 and MePGE2 were estimated. Infusion of the PGE2 precursor, arachidonic acid, elevated plasma fibrinogen, but fibrinogen response to 0.5-9 mg/kg arachidonic acid was unrelated to dose and half that given by 3 mg/kg PGE2. Slow infusion of several other fatty acids raised plasma fibrinogen as effectively as arachidonic acid, but prostaglandins D2 and F2alpha had only a slight effect. Infusion of 30 times the indomethacin dose that blocks platelet prostaglandin synthetase did not alter the plasma fibrinogen response to arachidonic acid. Indomethacin did not inhibit plasma fibrinogen elevations following ACTH or endotoxin infusion, or subcutaneous turpentine injection. Intravenous infusion of two cyclic ether prostaglandin endoperoxide analogs, (15S)-hydroxy-9alpha, 11alpha-(epoxymethano) prosta-5Z, 13E-dienoic acid, and (15S)-hydroxy-11alpha, 9alpha(epoxymethano) prosta-5Z, 13E-dienoic acid, failed to increase plasma fibrinogen.


A histochemical and ultrastructural study of adenocarcinoma of the lung. Twenty-five cases of solitary nodular adenocarcinoma of the human lung were studied histochemically and ultrastructurally and their morphological characteristics were compared to the cells observed in the control lungs. Adenocarcinoma cells of the human lung may be classified into following four types: Type A--cells resembling the bronchial goblet cell; Type B--cells resembling the mucous cell of the bronchial gland; Type C--cells resembling the type II alveolar lining cell; and Type D--cells resembling the nonciliated bronchiolar cell. Twenty-one cases belonging to Type D (84%) and two cases to Type B (8%), and one case each to Types A (4%) and C (4%). For the histogenesis of adenocarcinoma of the human lung, nonciliated bronchiolar epithelium may be the most important. A comparison of 10 cases of bronchiolo-alveolar carcinoma with 15 cases of ordinary (acinar and papillary) adenocarcinoma revealed no clear differences either histochemically or ultrastructurally.


Malignant fibrous histiocytoma. Clinicopathologic and ultrastructural study of 12 cases. The clinical and pathologic findings of 12 cases of malignant fibrous histiocytoma of the soft tissues are presented. The mean age of the patients (eight males and four females) was 64 years, and there was a strong predilection for localization in the extremities (10 cases). The lesion is of rather low-grade malignancy, with metastases in only a minority of cases (three cases) but with nonetheless a marked tendency for local recurrence (nine cases). Histologically, the essential feature of the tumor is its biphasic composition with both histiocytic and fibroblastic components, the latter showing a characteristic storiform pattern. In addition, a variable number of xanthomatous cells and multinucleated giant cells were observed. Ultrastructural studies confirmed the presence of the aforementioned cells and in addition revealed a primitive mesenchymal cell. It is suggested that this cell may be a primitive histiocyte from which the two main cellular components of the tumor arise.


Neuropathy in joggers.

Neuropathy in joggers. We have reported upon three different mononeuropathies that we believe were directly attributable to jogging. At this time it is presumed that this complication is not common, but as jogging increases as a routine form of exercise for the general populace it is possible that more such neuropathies will be seen. Mechanical injuries in runners are well described, and it is possible that as yet unidentified mechanical factors may injure neural tissue as well.


Inflammatory fibrous histiocytoma (? anthogranuloma). Report of two cases with ultrastructural observations in one. Two cases of inflammatory fibrous histiocytoma are presented, one occupying the pleural space, and the other the retroperitoneum. One of the cases was studied with the electron microscope and confirmed the histiocytic and xanthomatous nature of the lesion. It is suggested that the term xanthogranuloma be replaced by fibrous histiocytoma, and that when a considerable inflammatory component is present in the stroma, a guarded prognosis be entertained. Ultrastructurally there are no distinctive features for the inflammatory variant of the fibrous histiocytoma.


Malignant cystosarcoma phylloides. Treatment and prognosis. Twenty-six cases of malignant cystosarcoma phylloides treated at The Charity Hospital of Louisiana were reviewed. No metastases to axillary lymph nodes was observed. The lesion appears to metastasize seldom, if ever, to lymphatics, and axillary dissection is seldom required. Local recurrence was common, however, and justifies wide resection of the primary. Mortality was related more to the size of the lesion than to other findings such as skin or muscle involvement. No lesion with less than three mitoses per ten high power fields and minimal stromal atypia proved fatal. Associated neoplasia was common, particularly in the opposite breast.


[Variation of the profile phenotype M of alpha-1-chymotrypsine : trial of interpretation (author's transl)]. Cross immunoelectrophoresis of serum A1AT (Pi M) shows "frequent" patterns with M2 less than M6 less than M4. Other "particular" patterns were found with M6 greater than M4 and M6 less than M2. The most often found patterns among the Negroid population in our study appeared dissimilar to that found among Caucasians. The "super-gene" concept and the variability of genetic flow may explain this difference. The "particular" patterns are often found in cord blood samples and in patients with hepatocarcinoma. They show similaritis between embryonic and cancerous processes. These different patterns also agree with the "super-gene" concept.


A rationale for treating hepatic adenoma. Hepatic adenomas are being seen in young women taking oral contraceptives with alarming frequency. In the United States it is estimated that at least five million women are taking oral contraceptives. Physicians should consider hepatic adenoma in the differential diagnosis of all menstruating females with right upper quadrant pain. An early diagnosis and proper treatment could be life-saving.


Medical management of home hemodialysis patients. Increased emphasis on home hemodialysis because of proposed changes in federal funding will result in dispersion of dialysis patients to areas geographically removed from a dialysis unit. Thus primary care of these patients will increasingly become the responsibility of physicians having little previous contact with dialysis. We review the diagnosis and treatment of common problems in the dialysis patient with emphasis on the major problem areas of vascular access and the cardiovascular, hematologic, and osseous complications of renal failure.


Splenoperitoneal anastomoses after application of collagenase to the splenic capsule of rats. In 200 Wistar rats the spleen was transposed into a pouch between the muscle layers of the left abdominal wall. Collagenase powder was applied to the spleen surface. After 12 to 24 hours an acute haemorrhagic inflammation was seen. Collaterals developed from the splenic parenchyma to the abdominal wall from the 10th day. They connected the portal venous system with the caval system.


Adhesive arachnoiditis after lumbar myelography. Of 1500 myelographies, 99 patients had subsequent myelographies from which the prevalence of adhesive arachnoiditis caused by the initial investigation could be calculated. Three different water-soluble contrast agents had been used in the initial study: Kontrast U (800 patients), Dimer-X (400 patients), and Conray (300 patients) and the subsets of patients restudied represented 6%, 8% and 8% respectively of the whole series. After the first myelography 68 patients had no operation, 31 patients had hemilaminectomy. Conray produced arachnoid changes in 71% of the nonoperated patients. This differed significantly from the 43% caused by Kontrast U, and the 27% evoked by Dimer-X. The same trend was evident in the operated subset. The severity of the arachnoid changes was greater after Conray. Analysis of the iodine content of the different contrast media and comparison with similar series suggested that hyperosmolarity of the agent was responsible for the changes.


[Calcium, cGMP and cAMP roles in thyroid regulation (author's transl)]. Cholinergic agents induce an accumulation of cGMP in thyroid tissue and inhibit cAMP accumulation and thyroid hormone secretion resulting from TSH action. The aim of the present work was to determine the respective roles of Ca++ and/or cGMP in these actions. The results show that two complementary mechanisms may be demonstrated: 1) cGMP activates phosphodiesterase activity and cAMP hydrolysis. 2) Independently of cyclic nucleotide concentrations, increased intracytoplasmic Ca++ directly inhibits TSH induced stimulated hormone secretion.


[The cardiovascular manifestations of mixed hyperlipidaemia. Revision of a series of 950 cases (author's transl)]. The cardiovascular consequences of mixed hyperlipideamia have been determined using a very large series of 950 cases. The early development and the prevalence of complications renders the disease severe, even in its minor forms of the grave forms of essential hypercholesterolaemia. Certain special features are worthy of mention:--the total loss of any parallelism between the biological severity and the development of vascular complications;--the probable role of slow pre-beta-lipoprotein in the determination of complications above all forms resistant to therapeutic reduction where its persistence is remarkable, which justifies the addition to known electrophoretic types III and II b a type, in the opinion of the authors just as common, with pre-beta-lipoprotein without any increase in L.D.L.


Action of thyrotropin on phosphate incorporation into thyroid proteins in vitro. It is now well established that cAMP is the intracellular mediator of many effects of thyrotropin on the thyroid. Greengard has postulated that all the effects of cAMP inside the cell are secondary to the phosphorylation of proteins by cAMP activated protein kinase(s). The purpose of our work is to define, in an intact cell system, the nature of the thyroid proteins, the phosphorylation of which is stimulated by cAMP and TSH.


[Biochemical study of normal and abnormal thyroid cells in tissue culture (author's transl)]. Thyrotropin induces the formation of a follicular structure of thyroid cells in tissue culture. It produces an increase in cyclic AMP content of thyrotropin treated cells. Thyrotropin induces on increase in iodine incorporation with the appearance of iodinated proteins which are mostly 19 S. thyroglobulin. In goiters, the level of cyclic AMP and the stimulation with thyrotropin differs from normal conditions indicating differences in cell metabolism and differences in the properties of the receptor. Thyrotropin also gives an increase in uridine incorporation in RNA and on increase not only in poly A but also in poly A-RNA associated with heavy polysomes. The level of poly A is higher in toxic adenoma and lower in microfollicular adenoma as compared to colloido nodular goiter which is in good agreement with our knowledge of thyroid cell metabolism.


Growth hormone secretion in Addison's disease. Growth hormone secretion has been evaluated in patients with Addison's disease given T.R.H., A.C.T.H. or Glucagon i.v., or L-DOPA p.o. In those with the idiopathic, auto-immune variety the mean response to glucagon and L-DOPA was reduced when compared with that documented for patients in whom tuberculosis caused the lesion. Growth hormone plasma concentrations barely changed after T.R.H. and A.C.T.H., irrespective of the aetiology of the disease.


Clinical response to therapeutic agents in poisoning from mercury vapor. Exposure to mercury vapors for an hour per working day over a period of 13 years produced in a thermometer manufacturer severe signs and symptoms of mercury poisoning. Complete disability developed insidiously over the last six months of employment. During the first two months of observation, the patient was treated in succession with three chelating agents: 2,3-dimercapto-l-propanol (BAL), D-penicillamine and sodium diethyldithiocarbamate (Dithiocarb). Each agent was administered initially for a period of approximately two weeks. A second course of therapy with BAL was administered for three days. Of the three complexing agents used, BAL gave the most dramatically favorable clinical response and yielded the highest urinary excretions of mercury. Dithiocarb was partially effective; d-pencillamine proved to be essentially ineffective. Analyses of the patient's sweat indicated that appreciable amounts of mercury were excreted by this route. Following the alleviation of the severe symptoms by BAL, the patient was placed on a regimen of daily sweats and physio-therapy for a protracted period of several months. On this latter regimen, the mercury levels in the urine, blood serum and sweat were decreased to within the normal ranges of values. The patient made a complete and uneventful recovery. In patients encountering psychotic and neurological disorders of undetermined etiology, consideration should be given to unsuspected or masked chronic exposure to mercury vapors as a possible cause.


Mixed longitudinal data on skeletal age from a group of Dutch children living in Utrecht and surroundings. The height and weight of 1132 children, aged 8.0--17.0 years studied in 1970--72 in a semi-longitudinal survey in the Dental Institute of Utrecht, are compared with similar data from the national Dutch survey of 1965. Children measured in 1970--72 are somewhat taller than, but have the same weight as, those of the same ages in 1965. The increase in height since 1965 appears to be primarily due to the sub-group enrolled in vocational (as opposed to general) education. The maximal yearly increments in height and weight of the girls occurred between 11.0 and 12.0 years, and between 12.0 and 13.0 years, respectively. For boys the maximal increments in height and weight occurred between 14.0 and 15.0 years. Using the Tanner-Whitehouse 2 method, the skeletal age of this group of children was determined and compared with similar data from British standards. The results of the twenty-bone skeletal age indicated that Dutch boys, and to a lesser extent, girls, mature slightly later than English children at the approximate age range of 10.0--13.0 years and 8.0--10.0 years, respectively. After this age they follow roughly the growth curve of the British standards. The annual increment in skeletal age, plotted with chronological age as a time base, shows a peak for boys as well as girls that coincides with peak height velocity. The Carpal skeletal ages of boys and girls are almost identical in all age-groups with those of the British children, while the RUS skeletal age shows a much greater variability in the different age-groups. The variation in mean velocity (maturity points) between the two populations appears to be more marked in the RUS bones than in the round bones. The TW 1 skeletal age of each subject was plotted against the total TW 2, RUS or Carpal skeletal ages of the same individual. Equations are given for converting TW 1 skeletal ages into total TW 2 or RUS skeletal ages.


[Polymyxin B biosynthesis and tricarboxylic acid cycle enzymatic activity]. Activity of pyruvate dehydrogenase (PDG), isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase and malate dehydrogenase was found in the extracts of the cells of Bac. polymyxa 153, an organism producing polymyxin B. Dependence of the activity of the above enzymes on the carbon source in the medium, aeration conditions, strain features and culture age was shown. A low level of polymyxin B biosynthesis was observed at high activity of PDG and dehydrogenases of the tricarbonic acid cycle. Increased antibiotic production was recorded against the background of decreases values of the above enzyme activities.


[Interferonogenic and antiviral activity of the double-stranded replicative form of phage f2 RNA in tissue culture and on animals]. Biological activity of a new natural interferon inductor, the replicative RNA form of phage f2 (RFf2) was studied. A possibility of using RFf2 for production of highly active interferon under conditions of superinduction providing an increase in the interferon yield by to 256--512 times as compared to the control samples was shown. The protective interferonogenic and antiviral effect of RFf2 in mice infected with Semliki forest virus (SFV) and tickborne encephalitis virus (TBEV) was studied on administration of the inductor by various routes. It was found that intraperitoneal administration of RFf2 in a dose of 10 gamma per a mouse protected the infected animals from death. It was accompanied by production of up to 1280 units/ml of interferon in the blood serum of the animals. Maximum protection of the animals from death under conditions of the experiment (80 per cent on infection with SFV and 65 per cent on infection with TBEV) was observed when the preparation was administered twice: 4 hours after the infection. Combined use of RFf2 with chemotherapeutics (rimantadine) increased the protective effect both in the tissue culture and in vivo.


[Serum enzymatic activity in oncological patients treated with carminomycin]. Karminomycin effect on the activity of some serum enzymes, such as hexokinase (HK), lactate dehydrogenase (LDG), its isoenzymes and glucose-6-phosphatase (G-6-P-ase) was studied. Biochemical assays were applied to 52 patients with neglected malignant tumors. The course dose of the drug was on the average 72mg. The objective antitumor effect was registered in 15 patients. A reliable increase in the values of LDG-5 and G-6-P-ase was observed after the treatment course in the combined group consisting of all the patients subjected to the biochemical assay. Normalization of the serum enzyme spectrum was observed in 15 patients effectively treated with karminomycin: activity of HK and the cathode fractions of LDG decreased. When treatment with karminomycin was ineffective (37 cases), the changes in the enzymatic activity recorded before the treatment further aggraviated. It was found that the level of G-6-P-ase in the patients' treated with karminomycin increased independent of the treatment effect which was probably associated with its toxic effect on the liver. The increase was reversible.


Cutaneous metastases from hepatomas.

Cutaneous metastases from hepatomas. Three cases of hepatomas metastasized to the skin in a series of 88 patients with hepatomas. The skin metastases differed from the usual dermal nodules, such as fibromas, inflammatory granulomas, and adnexal tumors, by their rather sudden appearance as solitary or multiple, nonulcerative, painless, firm, reddish-blue nodules on the scalp, chest, and shoulder. Biopsies of these nodules were necessary in order to confirm the diagnosis of the cutaneous metastases, which appeared before the primary tumors were recognized. Microscopically, the skin tumors were adenocarcinomas in two instances and hepatocellular carcinoma in one. The skin metastases were a late manifestation of the primary tumors; the patients died within three weeks to six months after the appearance of skin tumors. Necropsies showed widespread metastases.


Kaposi's varicelliform eruption in mycosis fungoides. Kaposi's varicelliform eruption, caused by herpes simplex type 1, developed in a patient with mycosis fungoides four days after initiation of photochemotherapy with methoxsalen plus long-wave ultraviolet light (PUVA). He had a history of recurrent localized herpes infection. Vidarabine (adenine arabinoside) was used as treatment. Rechallenge with PUVA did not provoke another herpes infection. Kaposi's varicelliform eruption is rare in mycosis fungoides. Vidarabine may prove to be useful in the treatment of widespread herpes simplex.


Multiple periorbital fibrous histiocytomas: a light and electron microscopic study. Recurrent, bilateral, multiple, periorbital fibrous histiocytomas occurred in a 62-year-old woman. There were no associated serum lipid abnormalities. Histologically, the tumor was composed of an admixture of lipid-laden histiocytes and fibroblasts with a variable amount of collagen production. In many areas the fibroblasts were arranged in a storiform pattern. No cytologic evidence of malignancy was observed. Ultrastructural studies of the tumor showed histiocytic cells with a variable amount of lipid in the cytoplasm and fibroblasts with mild to moderate collagen production. Differential diagnosis and histogenesis are discussed.


Sézary's syndrome: report of a case showing peripheral neuropathy and bone marrow fibrosis. A case of Sézary's syndrome occurred in a 45-year-old man. The unusual noteworthy features in this case are dermal sclerosis, peripheral neuropathy, and bone marrow fibrosis. In two other cases, reviewed here, there was a tendency to fibrosis; therefore, we propose that this process may be an integral part of Sézary's syndrome.


Isolated ACTH deficiency. Metabolic and endocrine studies in a 7-year-old boy. Metabolic and endocrine studies on a 7-year-old boy who presented with hypoglycaemic convulsions are reported in detail, proving the diagnosis of isolated ACTH deficiency--a rare cause of hypoglycaemia in childhood. Adrenaline secretion during insulin-induced hypoglycaemia was reduced. Low blood alanine levels occurred during starvation-induced hypoglycaemia, together with raised total blood ketone bodies; blood glucose did not increase adequately after oral alanine at this time. Hypoglycaemia in isolated ACTH deficiency appears to be due to a combination of impaired alanine mobilisation and a decreased rate of gluconeogenesis.


Congenital cytomegalovirus infection in newborn infants of mothers infected before pregnancy. The rate of congenital cytomegalovirus (CMV) infection was studied in newborn infants in an African population in which all adults had experienced primary CMV infection during childhood. Viruria within the first 12 hours after delivery was taken as evidence of prenatal CMV infection. 28 of 2032 newborn infants examined had viruria, giving a rate of 1.4% congenital CMV infection. The presence of meternal serum antibody therefore appears not to protect the fetus from intrauterine infection. Either reactivation of latent maternal CMV infection or recurrence of infection during pregnancy despite the presence of serum antibodies may explain these findings. Whether the long-term effects of CMV infection acquired in utero differ in cases of primary maternal infection from those due to reactivated or recurrent infection in seropositive mothers, remains undecided. Thus, the value of a live CMV vaccine to prevent prenatal CMV infection may be questioned.


Interaction of ACTH, corticosterone and cyclic nucleotides in Harding-Passey melanoma melanogenesis. The acute in vitro action of adrenocorticotropin (ACTH) and corticosterone alone and in combination were determined in the Harding-Passey (HP) melanoma grown in vivo. Hormone treated melanoma dice (5--240 min) were analyzed for tyrosinase activity, cyclic AMP (cAMP) and cyclic GMP (cGMP). ACTH elevated cAMP and cGMP levels 20- and 13-fold, respectively, in the HP melanoma. However, these large increases in cyclic nucleotide levels were accompanied by only a 49% increase in tyrosinase activity. Corticosterone elicited a similar response. ACTH plus corticosterone produced an early cAMP and cGMP peak followed by depression. ACTH plus corticosterone stimulated tyrosinase activity coincident with the early cyclic nucleotide peak followed by a drop in tyrosinase activity which was subsequently elevated. The results indicate that neither cAMP nor cGMP are the sole modulators of tyrosinase activity and suggest the interaction of ACTH, corticosterone and cyclic nucleotides in the regulation of melanoma tyrosinase activity.


DNA-binding proteins of psoriatic scales III. Biochemical characterisation as non-histone-proteins. Histone and non-histone-proteins (NHP) are proteins with a specific affinity to DNA; each group is involved in the regulation of gene expression in its own way. To investigate molecular biologic processes at psoriasis, DNA-binding proteins (DBP) were isolated from psoriatic scales. During this work the proportions of histone and NHP of the DBP fractions were examined. Using two different methods (Bio Rex 70-chromatography and isoelectrofocussing), it was found that the isolated DBP contain only acidic proteins. Likewise, the composition of amino acids is comparable with those of acidic, nuclear proteins of other tissues. Thus the isolated DBP represent to its greatest extent acidic, chromosomal NHP, which obviously are derived from the preserved nuclei of the parakeratotic scale layer.


Cyclic AMP and prostaglandin E in perfusates of rat hind paws during the development of adjuvant arthritis. The contralateral uninjected hind paws of rats which had been injected with Freund's complete (FCA) or incomplete (FIA) adjuvant 10,14, 18, or 22 days previously were perfused under urethane anaesthesia using a stainless steel coaxial catheter. In one series of experiments cyclic AMP (cAMP) levels were determined after a 2-hour perfusion. cAMP levels were also determined in rats treated on days 16-22 with either prostaglandin E(1) (PGE(1)) (500 mug/kg per day subcutaneously) or saline. When compared with control rats injected with FIA, after 22 days, cAMP levels in FCA-injected rats fell between days 10 and 18 and then rose between days 18 and 22. After PGE(1) treatment, paw volume on day 22 increased in rats injected with FCA, but cAMP levels were not significantly altered when compared with day 22 FCA-injected controls treated with saline. In a second series of experiments, using a slightly modified perfusion method, PG levels in extracts of 30-minute perfusates were determined after chromatography and bioassay. Protein levels and paw volume were also measured. No PGF was detectable in any perfusate. Changes in PGE levels in FCA-injected animals paralleled changes in paw volume, increasing from day 14 and reaching a maximum on day 22. Both parameters remained unchanged in FIA-injected rats. Protein levels in perfusates from FCA-injected animals were significantly greater than FIA-injected controls only on day 22. We suggest that the early changes in cAMP reflect the infiltration of activated leucocytes into the inflamed joint and that the increase in PGE is attributable to lysosomal enzyme activity. Later increases in cAMP are attributable both to the increasing PGE levels and to other changes in cellular activation. We suggest that high levels of PGE contribute to tissue damage which is reflected in raised protein levels.


Clinical manifestations of infections with herpesviruses after kidney transplantation: a prospective study of various syndromes. Herpesviruses infections occur commonly following kidney transplantation and immunosuppression, and contribute substantially to morbidity in the transplant recipient. In this prospective study, stomatitis, mononucleosis, hepatitis, or interstitial pneumonia occurred in 24 of 30 patients (80%) as a result of reactivation of latent herpesvirus infections, but the majority of these syndromes were self-limited and the infections were often asymptomatic. Rejection occurred significantly more frequently in CMV-infected patients, but a distinct causal relationship cannot be deduced.


The effect of glucagon on rat cardiac cyclic AMP, phosphorylase a and force of contraction. Glucagon produced dose-dependent increases in cyclic AMP, contractile force and % phosphorylase a when injected into isolated perfused rat hearts. Time-response experiments demonstrated that the increase in cyclic AMP occurred prior to changes in the other two parameters. All glucagon effects were enhanced by perfusion of the hearts with 1.0 mM theophylline although contractile force was affected less than the other 2 events. The data lend support to the concept that increases in cyclic AMP may be involved in the inotropic effect of glucagon. It should be noted, however, that the cyclic AMP increases produced by glucagon were considerably less than those previously noted with either the catecholamines or histamine.


The K+-dependent phosphatase from human renal tissue: its properties and time dependent inhibition by ouabain. The K+-dependent p-nitrophenyl phosphatase activity associated with human renal (Na+ + K+)-ATPase was examined for some of its kinetic properties. ATP inhibited the K+-dependent phosphatase and raised the Km for p-nitrophenylphosphate. Stimulation of the K+-dependent phosphatase by K+ was blocked by Na+ in a noncompetitive manner. Inhibition of the K+-dependent phosphatase by ouabain was dependent upon incubation time. The apparent Kï was 2.0 micron.


Disordered glucose and insulin metabolism in patients with insulinoma. The response of plasma glucose and insulin to infusion of glucose and of epinephrine plus propranolol were examined in normal subjects and in two patients with surgically proven insulin-secreting islet cell tumors. The plasma immunoreactive insulin concentration in the two patients was both inappropriate and independent of the plasma glucose concentration. Their insulin secretion was neither increased by physiologic stimulants nor decreased by pharmacologic inhibitors of insulin secretion. There are diagnostic uses for these data as well as theoretical implications. We propose a physiological approach to establish the diagnosis of insulin-secreting islet cell tumors.


[Concentrations of the IgM and antibodies for the TORCH complex in the umbilical blood (author's transl)]. The Authors have found both IgM and antibodies for the TORCH complex in the umbilical blood of 1500 newborns. In 119 (7.9%) there was an increase of IgM. In 23% of these newborns there were present antibodies for rubella, in 21% antibodies for toxoplasma, in 15.9% antibodies for cytomegalovirus, and in 19.2% antibodies for herpes simplex. However there was no statistical correlation between the antibodies for the TORCH complex and the increase of IgM.


Normal jejunal cyclic nucleotide content in a patient with secretory diarrhea. A case of chronic secretory diarrhea with elevated plasma vasoactive intestinal peptide (VIP) and serum gastrin levels is described. Plasma secretin, glucagon, insulin, and cyclic adenosine and guanine monophosphate (cAMP and (CGMP) concentrations were normal. Administration of a prostaglandin synthetase inhibitor failed to decrease the volume of diarrhea. There was no evidence of laxative abuse, antral cell hyperplasia, gastric hypersecretion, or pancreatic hypersecretion. The pancreatic histology was interpreted as islet cell hyperplasia. Jejunal tissue cAMP and cGMP concentrations were in the same range as those obtained from three control subjects. This report suggests that cyclic nucleotides may not mediate intestinal secretion in hormone-induced diarrhea.


[Isolation of foamy virus type II out of haematopoetic cells from baboons with haematoblastoses and from healthy animals (author's transl)]. Foamy virus Type II persists in the haematopoetic organs of 75 percent of baboons in the Suchumi flock. A mixed infection with foamy virus types I and II seems to be possible. Foamy viruses are isolated as well from monkeys with haemoblastoses as from healthy animals. New information concerning the intrauterine transmission of foamy viruses were obtained.


[The diagnosis of the main histological types of lung cancer by means of cytological smears (author's transl)]. The paper emphasizes the possibility to distinguish types I, II and III (WHO classification) of lung cancer not only by means of single cells, but also of tissue solids in cytological smears. The morphologic criteria of tissue solids and their special patterns in the different main types of lung cancer are described.


Medullary carcinoma of the thyroid. Giant cell type. This report presents a rare histological variation of medullary (C-cell) carcinoma of the thyroid, referred to as giant cell type, which is similar to that found in anaplastic carcinoma of the thyroid, or choriocarcinoma. The giant cells in this case possessed specific immunofluorescence for calcitonin and secretory granules in the cytoplasm. The giant cells were tumor cells of medullary carcinoma and could be distinguished from anaplastic carcinoma of the thyroid by various histological characteristics, such as nuclear invagination, an intermingled pattern of giant cells with typical small solid cells, infrequency of mitosis, and the existence of amyloid stroma.


[Morphology of the adrenal cortex in infants with generalized adenovirus infections]. Morphometric, histological, and immunofluorescent studies were carried out with adrenal glands of 14 infants dying with generalized adenovirus infection sometimes concurrent with other acute viral respiratory diseases. Nonspecific changes were found: edema of the capsule and stroma, discomplexation of the trabeculae, circulatory disorders, delipoidization, an increase in the content of DNA and RNA in cells of the definitive cortex, resorption of the elements of the fetal cortex. The pattern of changes of morphometric values attests to increased functional activity of the adrenal cortex. The intensity of the observed changes was directly related to the duration of the disease. The results of clinico-morphological analysis confirm the importance of adrenal insufficiency in tanatogenesis in generalized adenovirus infection. In 10 cases epithelial and endothelial cells of the definitive cortex were found to have specific lesions, the so-called adenovirus cells.


[Lesion of the thymus gland in infants caused by cytomegalovirus]. In the autopsy materials of 1972-1976, cytomegaly was diagnosed in 47 infants dying in the first year of life; two of them were found to have cytomegalovirusinvolvement of the thymus. The clinical course of the disease depended on the intensity of pathological lesions in organs and tissues associated with secondary infection. In the thymus, alongside with marked accidental involution, cytomegaloviral metamorphosis of the reticular epithelium and epithelium of Hassal bodies was found. Foci of calcinosis were observed in the parenchyma of the thymus. During the disease hypogammaglobulinemia was observed. A possible role of cytomegalovirus infection in the development of acquired immunodeficiency conditions in infants under one is suggested.


Conduction studies of the saphenous nerve in healthy subjects. An easily performed and reproducible method is described for the antidromic determination of conduction velocity in the saphenous nerve. Eighty nerves were studied in 40 healthy subjects and the mean values obtained were as follows: latency 3.6 +/- 0.4 msec, conduction velocity 41.7 +/- 3.4 m/sec, amplitude 9.0 muV. This new technique should be useful in the electrodiagnostic evaluation of peripheral neuropathy, femoral neuropathy and saphenous nerve entrapment syndrome.


[Ultrastructure of intracellular storage materials in an autopsy case of adult-onset metachromatic leucodystrophy (MLD) (author's transl)]. Formalin-fixed samples from the demyelinated frontal white matter of an autopsy case of adult-onset MLD were studied by electron microscopy. The intracellular storage materials exhibited the following types of structural patterns: (I) ordinary myelin figures; (II) pleated myelin figures; (III) narrow stacks of lamellar discs which were most likely components of formerly compact "prismatic" inclusions; (IV) paired lamellae, either arranged in loose parallel arrays or scattered about in random directions; (V) piles of parallel lamellae with alternating electron-dense and electron-lucent inter-spaces; and (VI) collections of structures resembling fragments of so-called pentalaminar membranes. Types I to IV have already been described in early-onset as well as late-onset forms of MLD, but types V and VI have not. Postmortem autolysis had possibly altered the structural organization of some cytoplasmic deposits and given rise to the formation of those lamellar patterns which were hitherto not known to occur in MLD.


The occurrence of human wart-virus antibodies in dogs, pigs and cattle. Using the immunodiffusion method, antibodies against human wart-virus were detected in dog, pig and cattle sera but not in horse and reindeer sera. Antibodies were found in 25 percent (28/114) of the dog sera, the prevalence of antibodies being fairly similar to that in children of the same age. By electron microscopy the antibodies in dog sera were shown to attach to and precipitate the human wart-virus particles, and in immunodiffusion the precipitation lines of human and dog sera were shown to be identical. Of the cattle sera studied, 10 percent (10/97) and of the pig sera 13 percent (5/40) gave a faint precipitation line, having identity with that given by the human sera, against human wart-virus. Conversely 18 percent (9/50) of adult human sera contained precipitating antibodies against a bovine papilloma antigen, probably bovine papilloma virus.


The detection of antibody to virus-infection associated (VIA) antigen in various species of African wildlife following natural and experimental infection with foot and mouth disease virus. The double immuno-diffusion (DID) test has been applied to detect antibody to VIA antigen in sera from various species of African wild ungulates. In conjunction with the serum neutralisation (SN) test it can be used to decide the degree of risk of movement of animals to other countries free from foot and mouth disease (FMD). The value of the test in assessing the history of infection is limited by its relatively low sensitivity and specificity in respect of virus type.


T-antigen expression in human skin fibroblasts is not regulated by an endogenous interferon response to SV40 infection. Exogenous interferon may affect SV40 T-antigen expression, depending on the chromosomal complement, time of treatment, and biological factors in human cells. However, no evidence was found for endogenous interferon response to SV40 infection in the regulation of T-antigen expression.


[Concomitant meningioma and glioblastoma. Report of a case]. A case of coincidental glioblastoma and meningioma in which the first manifestation were focal convulsive fits is reported. As the association of intracranial tumors is infrequent, their clinical ways of presentation and the theories on their origin are discussed, as well as the importance of the preoperative diagnosis for the surgical planning and prognosis.


[Local cellular and tributary lymphocyte immunity in cancer of the breast. Diagnostic and prognostic evaluations]. Following a review of the literature on breast cancer and local and lymph gland immunoreactive state, the results of histomorphological study on a series of 150 cases of breast and axillary lymphnode cancer with and without metastasis, are reported. On the basis of findings, stress is laid on the importance of a more specific assessment of the histomorphological picture (degree of malignity) and the local and tributary lymph node immuno-reactive condition in the interest of a more specific prognostic evaluation.


Polyneuropathy and folate deficiency.

Polyneuropathy and folate deficiency. We studied five patients (two men and three women, age between 58 and 76 years) with clinical and electrophysiological signs of polyneuropathy. Routine neurological, hematological, and gastroenterological studies as well as procedures to test fat malabsorption were performed. Folate determinations were done using both radioactive and Lactobacillus casei methods. Two patients displayed the signs of subacute combined degeneration of the spinal cord with polyneuropathy, while three had only signs of neuropathy. All had low serum folate concentration, long-standing gastrointestinal disease, and deficient folate intake. The D-xylose absorption test gave values in all patients, while none displayed the classical malabsorption syndrome. The patients had substantial improvement or recovered (according to clinical and electrophysiological measurements) after periods ranging from 9 to 39 months of folate therapy. Such acquired folate-responsive polyneuropathy has two principal characteristics: mixed sensorimotor with mainly sensory deficits, and involvement of one or both of the lower extremities much more extensively than the upper extremities.


Decreased spinal cord cGMP in murine (wobbler) spontaneous lower motor neuron degeneration. Of the secondary messengers, cyclic quanosine monophosphate, but not cyclic adenosine monophosphate, was reduced by 80% in the cervical spinal cord and by 56% in the cerebellum of clinically affected homozygote "wobbler" mice compared to sex- and age-matched litter-mate clinically unaffected control mice. A neurotransmitter, gamma aminobutyric acid, and high-energy intermediates, adenosine triphosphate and phosphocreatine, were not significantly different in affected or unaffected mice.


Malignant salivary gland tumors of the palate. Twenty patients with malignant salivary gland tumors of the hard and soft palate were seen at the University of Virginia Hospital from 1956 through 1975. The characteristics of the tumors, including symptoms and histology are reviewed and the results of treatment are analyzed. In particular, the place of radiotherapy in their management has been examined. Primary control by initial surgery alone was achieved in 60% (9/15) of the cases, and, when those patients who received radiotherapy for residual disease or salvage are included, the primary control was 94% (16/17). Five- and ten-year determinate survival rates were 88% and 67%, respectively. From this retrospective analysis and a review of the literature, it appears that radiotherapy has made a very positive contribution to the management of these tumors.


Perinatal foal mortality associated with a herpesvirus. An outbreak of perinatal foal mortality associated with a herpesvirus is described. Twenty two foals either were still-born, or died soon after birth, or were weak and soon developed severe respiratory signs, or were normal at birth and developed respiratory symptoms 18 to 24 hours later. Elevated temperatures, heart and respiratory rates were constant features. The animals were severely leucopaenic, and showed an absolute neutropaenia. At autopsy the lungs were enlarged, and showed varying degrees of aeration and moderate to severe oedema and congestion. Histopathology showed an acute focal necrotising bronchiolitis with the presence of intranuclear eosinophilic inclusion bodies. Herpesvirus was recovered from 9 foals in cell culture and identified by electron microscopy.


Diarrhoea in piglets inoculated with rotavirus. A rotavirus isolated from a field outbreak of diarrhoea in artificially reared piglets was purified, filtered and administered orally to gnotobiotic and conventional piglets. Four successive passages of the virus in gnotobiotic piglets produced severe diarrhoea within 20 to 24 hours of administration. The diarrhoea lasted several days causing dehydration, emaciation, loss of body weight and some deaths. Virus was demonstrated in the faeces of the infected piglets by electron microscopy. Conventionally reared piglets developed little or no diarrhoea when given virus, whereas artificially reared piglets developed moderate to severe diarrhoea which lasted from 3 to 8 days with some deaths. No clinical disease was obvious in surviving piglets following challenge with the virus 10 or 17 days after initial infections.


Spinal cord compression caused by a metastatic lesion from an aortic body tumour. An aortic body tumour in a 7-year-old wire-haired fox terrier with hind limb ataxia is described. A metastatic lesion in the dorsal arch of the eighth thoracic vertebra caused compression of the spinal cord. Radiographic techniques are discussed that enabled the position and extent of the primary tumour and its metastasis to be defined and allowed a provisional diagnosis of chemodectoma.


Stimulation of the respiratory chain of rat liver mitochondria between cytochrome c1 and cytochrome c by glucagon treatment of rats. Mitochondria from glucagon-treated rats oxidize succinate, but not ascorbate plus tetramethylphenylenediamine, faster in the uncoupled state than do control mitochondria. The rate of O(2) uptake in the presence of both substrates is equal to the sum of the rates of the O(2) uptake in the presence of either substrate alone. It is concluded that the mitochondrial respiratory chain is limited at some point between cytochromes b and c and that this step is regulated by glucagon. Measurement of the cytochrome spectra under uncoupled conditions in the presence of succinate and rotenone demonstrates a crossover between cytochromes c and c(1) when control mitochondria are compared with those from glucagon-treated rats, cytochrome c being more oxidized and cytochrome c(1) more reduced in control mitochondria. Under conditions where pyruvate metabolism is studied the control mitochondria are generally more oxidized than those from glucagon-treated rats, the redox state of cytochrome b-566 correlating with the rate of pyruvate metabolism in sucrose medium. However, when the redox state of the mitochondria is taken into account, a crossover between cytochromes c and c(1) is again apparent. The spectra of the b cytochromes are complex, but cytochrome b-562 appears to become more reduced relative to cytochrome b-566 in mitochondria from glucagon-treated rats than in control mitochondria. This can be explained by the existence of a more alkaline matrix in glucagon-treated rats, the redox potential for cytochrome b being pH-sensitive. It is concluded that glucagon stimulates electron flow between cytochromes c(1) and c. The physiological significance of these findings is discussed.


Adenosine 3':5'-cyclic monophosphate-dependent protein kinase(s) of rat ovarian cells. Gonadotropin regulation of adenosine 3':5'-cyclic monophosphate-receptor activity. Regulation of cyclic AMP-dependent protein kinase, cyclic AMP-receptor activity and intracellular cyclic AMP concentrations by choriogonadotropin was studied in ovarian cells prepared from 26-day-old rats. A close correlation was observed between phospho-transferase activity and cyclic AMP-receptor activity in 12000g supernatant fractions from rat ovarian homogenate. The apparent activation constant (K(a)) and I(50) (concentration required to produce 50% inhibition) of different cyclic nucleotides for phosphotransferase and cyclic AMP receptor activities respectively were also determined. Cyclic AMP and 8-bromo cyclic AMP were most effective, giving K(a) values of 0.08 and 0.09mum and I(50) of 0.12 and 0.16mum respectively. Other nucleotides were also effective, but required higher concentrations to give a comparable effect. An increased concentration of cyclic AMP produced by choriogonadotropin (1mug/ml) treatment was accompanied by decreased cyclic AMP binding as early as 5min after hormone addition. Choriogonadotropin also stimulated the protein kinase activity ratio (-cyclic AMP/+cyclic AMP) under identical experimental conditions. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine potentiated the action of choriogonadotropin on the three parameters measured in a dose- and time-dependent manner. The maximal cyclic AMP-binding capacity, as determined by cyclic AMP-exchange assay, remained unchanged before and after hormone addition. The endogenously bound cyclic AMP was determined from the difference between the maximal binding capacity and the exogenously bound cyclic AMP. With different choriogonadotropin concentrations, a quantitative correlation was established between maximal binding capacity, exogenous binding and endogenous binding activities. Approx. 60% of total binding sites were endogenously occupied in untreated cells, and choriogonadotropin (1mug/ml) treatment fully saturated available binding sites with a parallel 10-fold increase in cellular cyclic AMP. The present results provide evidence for a probable intracellular compartmentalization of cyclic AMP in the ovarian cell, and suggest that in the unstimulated state all cyclic AMP present in the ovarian cell may not be available for protein kinase activation.


The role of creatine kinase and arginine kinase in muscle. Arginine and creatine kinase activities in different muscles are compared with calculated maximum rates of ATP turnover. The magnitude of the kinase activities decreases in the following order: anaerobic muscles and vertebrate skeletal muscles greater than heart muscle greater than insect flight muscle. The maximum activity of phosphagen kinases (i.e. creatine kinase and arginine kinase), in the direction of phosphagen formation, is lower than the calculated maximum rate of ATP turnover in insect flight muscle or rat heart.


The role of phospholipids in the reduction of ubiquinone analogues by the mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase complex. The isolated NADH-ubiquinone oxidoreductase complex of bovine heart mitochondria reduces ubiquinone analogues by two pathways. One pathway is inhibited by rotenone, and reduction of quinones takes place in the lipid phase of the system. The other pathway is insensitive to rotenone and reduction takes place in the aqueous phase. The variation of rates of electron transpport with the chemical nature of the quinone analogue and the concentrations of both quinone and phospholipid can be rationalized in terms of partition of the quinone between the aqueous and lipid phases of the system. Thus one function of phospholipid associated with the enzyme appears to be to act as solvent for ubiquinone reduced by the rotenone-sensitive pathway. This proposal is supported by the kinetic behaviour of enzyme whose endogenous lipids have been replaced by (1,2)-dimyristoylsn-glycero-3-phosphocholine. Thus, under certain circumstances, the rotenone-sensitive reduction of ubiquinone-1 exhibited a substantial increase in activation energy below the phase-transition temperature of the synthetic lipid, whereas the reduction of other acceptors was unaffected.


Effects of hormones and N6O2'-dibutyryl-adenosine 3' :5'-cyclic monophosphate, administered in vivo, on phosphate transport and metabolism in isolated rat liver mitochondria. 1. The administration of glucagon or N6O2'-dibutyryl cyclic AMP to fed rats by intraperitoneal injection was associated with a 2-fold increase in the amounts of endogenous Pi and ATP, and an increase in the rate and extent of transport of exogenous Pi (measured in either the presence or the absence of Ca2+) in mitochondria subsequently isolated from the liver. No change was observed in either the maximum rate of transport of exogenous Pi or in the rate of 32Pi exchange. 2. The changes induced by glucagon and dibutyryl cyclic AMP were markedly decreased by the co-administration of cycloheximide. 3. The administration of insulin to rats resulted in an increase of about 1.3-fold in the concentration of endogenous mitochondrial Pi 4. The amounts of endogenous Pi in mitochondrial isolated from the livers of starved rats were 3 times those in mitochondria isolated from fed animals. 5. It is concluded that the liver mitochondrial phosphatetransport system may be an important site of hormone action. 6. In the course of these experiments, it was shown that Ca2+ markedly stimulates mitochondrial phosphate transports.


The reaction of Pseudomonas aeruginosa cytochrome c-551 oxidase with oxygen. The reaction of ascorbate-reduced Pseudomonas cytochrome oxidase with oxygen was studied by using stopped-flow techniques at pH 7.0 and 25 degrees C. The observed time courses were complex, the reaction consisting of three phases. Of these, only the fastest process, with a second-order rate constant of 3.3 X 10(4) M-1.S-1, was dependent on oxygen concentration. The two slower processes were first-order reactions with rates of 1.0 +/- 0.4s-1 and 0.1 +/- 0.03s-1. A kinetic titration experiment revealed that the enzyme had a relatively low affinity constant for oxygen, approx. 10(4)M-1. Kinetic difference spectra were determined for all three reaction phases, showing each to have different characteristics. The fast-phase difference spectrum showed that changes occurred at both the haem c and haem d1 components of the enzyme during this process. These changes were consistent with the haem c becoming oxidized, but with the haem d1 assuming a form that did not correspond to the normal oxidized state, a situation that was not restored even after the second kinetic phase, which reflected further changes in the haem d1 component. The results are discussed in terms of a kinetic scheme.


Mechanism of oxyhaemoglobin breakdown on reaction with acetylphenylhydrazine. The reaction of oxyhaemoglobin and acetylphenylhydrazine, which results in haemoglobin denaturation and precipitation, was found to be influenced by H202 and superoxide (O2-.) generated during the reaction. By analysing the different haemoglobin oxidation products, it was found that by influencing the rate at which oxyhaemoglobin was oxidized, H2O2 accelerated the overall haemoglobin breakdown, and O2-. inhibited it. By adding GSH (reduced glutathione) or ascorbate, it was possible to slow down the rates of both oxyhaemoglobin oxidation and O2-. production, and the overall rate of haemoglobin breakdown. These results are compatible with a mechanism involving production of the acetylphenylhydrazyl free radical, and with GSH, ascorbate and O2-. acting as radical scavengers and preventing its further reactions. The reaction produced choleglobin, as well as acetylphenyldiazine and methaemoglobin, which combined to form a haemichrome. The haemichrome was less stable and precipitated first. It was also less stable than the haemichrome formed by direct reaction of acetylphenyldiazine with methaemoglobin, and it is proposed that this is because the methaemoglobin produced from oxyhaemoglobin and acetylphenylhydrazine was modified by the free radicals and H2O2 produced in the reaction.


Electron-paramagnetic-resonance studies on nitrogenase of Klebsiella pneumoniae. Evidence for acetylene- and ethylene-nitrogenase transient complexes. Klebsiella pneumoniae nitrogenase exhibited four new electron-paramagnetic-resonance signals during turnover at 10 degrees C, pH7.4, which were assigned to intermediates present in low concentrations in the steady state. 57Fe-substituted Mo--Fe protein showed that they arose from Fe--S clusters in the Mo--Fe protein of nitrogenase. The new signals are designated: Ic, g values at 4.67, 3.37 and approx. 2.0; VI, g values at 2.125, 2.000 and 2.000; VII, g values at 5.7 and 5.4; VIII, g values at 2.092, 1.974 and 1.933. The sharp axial signal VI arises from a Fe4S4 cluster at the --1 oxidation level. This signal was only detected in the presence of ethylene and provides the first evidence of an enzyme--product complex for nitrogenase. [13C]Acetylene and [13C]ethylene provided no evidence for direct binding of this substrate and product to the Fe--S clusters giving rise to these signals. The dependence of signal intensities on acetylene concentration indicated two types of binding site, with apparent dissociation constants K less than 16 micron and K approximately 13mM. A single binding site for ethylene (K=1.5mM) was detected. A scheme is proposed for the mechanism of reduction of acetylene to ethylene and inhibition of this reaction by CO.


Studies on the time course and rate-limiting steps in the activation of adenylate cyclase in rat liver by cholera toxin. Cholera toxin stimulates adenylate cyclase in rat liver after intravenous injection. The stimulation follows a short latent period of 10min, and maximum stimulation was attained at 120min. Half-maximal stimulation was achieved at 35min. In contrast with this lengthy time course in the intact cell, adenylate cyclase in broken-cell preparations of rat liver in vitro were maximally stimulated by cholera toxin (in the presence of NAD+) in 20min with half-maximal stimulation in 8min. Binding of cholera toxin to cell membranes by the B subunits is followed by translocation of the A subunit into the cell or cell membrane, and separation of the A1 polypeptide chain from the A2 chain by disulphide-bond reduction, and finally activation of adenylate cyclase by the A1 chain and NAD+. As the binding of cholera toxin is rapid, two possible rate-limiting steps could be the determinants of the long time course of action. These are translocation of the A1 chain from the outside of the cell membrane to its site of action (this includes the time required for separation from the whole toxin) or the availability of NAD+ for activation. When NAD+ concentrations in rat liver were elevated 4-fold, by the administration of nicotinamide, no change in the rate of activation of adenylate cyclase by cholera toxin was observed. Thus the intracellular concentration of NAD+ is not rate-limiting and the major rate-limiting determinant in intact cells must be between the time of toxin binding to the cell membrane and the appearance of subunit A1 at the enzyme site.


Binding of ligands and spectral shifts in cytochrome c oxidase. 1. On addition of reductant (ascorbate plus NNN'N'-tetramethyl-p-phenylenediamine) to isolated cytochrome c oxidase (ox heart cytochrome aa(3)), in the presence of the inhibitors azide or cyanide, an initial partially reduced species is formed with absorption peaks at 415nm, 445nm and 605nm, which slowly gives rise to the final ;half-reduced' species in whose spectrum the 415nm peak has disappeared and a new absorption is seen at 430-435nm. 2. In the absence of reductant, cyanide forms an initial complex with the enzyme with a spectrum similar to that of the uncombined form, which slowly changes into the ;low-spin' cyanide form with a peak at 432nm. Azide, in absence of reductant, shifts the Soret peak slightly, but the resulting complex, which is probably thermally ;mixed-spin', undergoes no further changes. 3. The Soret-peak shift of oxidized cytochrome a(3) which occurs on reduction of the enzyme in the presence of azide is accompanied by a concurrent blue shift of the ferrous cytochrome a peak from 605nm to 603nm. A partial blue shift of the alpha-peak occurs in the half-reduced sulphide-inhibited enzyme, and a complete blue shift is seen in the analogous complexes with alkyl sulphides [a(2+)a(3) (3+)HSR compounds, where R=CH(3), C(2)H(5) or (CH(3))(2)CH]. 4. Analogous, albeit less readily decipherable, spectroscopic effects with the ligands imidazole and alkyl isocyanides suggest that on reduction of cytochrome a an interaction occurs between the two haem groups involving (i) a high- to low-spin change in cytochrome a(3), and after this, (ii) a change in the molecular environment of the cytochrome a. The latter effect, possibly a decrease in the hydrophobicity of the haem pocket, requires that the ligands on cytochrome a(3) have a bulky and partially hydrophobic character.


[Hepatocarcinoma in an 18 month old patient]. The patient was an 18 month old female showing a mass in the right upper quadrant. At the examination, in epigastrium and right hypochondrium, a soft tumor mass embodied to the liver was felt. The patient was operated after laboratory studies including an hepatogram were done, but without having determined alpha phetoglobulin. A 15 X 15 cms. spherical mass was found forming body with the left lobe of the liver and was removed together with the lobe. The pathological diagnosis was of hepatocarcinoma, according to ishak and Glunz's classification. All this leads to comment how interesting is the determination of serological tests for alpha phetoglobulins as a measure to aid in the diagnosis. Likewise, the surgical management carried out is a determinant measure for the treatment of these tumors. At present, survivals up to 6 years may be offered. The reason why this case is reported is because hepatocarcinoma is very uncommon at this age.


Age-dependent changes in the activities of ATPase and some pyridine nucleotide-linked enzymes in the chick testis. The ontogeny of some of the enzymes connected with carbohydrate metabolism in the testis were studied in the White-Rock chicks. In the first place testicular growth in these chicks relate to their overall growth as measured by their body weights. ATPase and NAD+-dependent succinic dehydrogenase activities decreased both with advancing age and increasing testicular weight. However, these enzymes showed maximum activities at 17 and 28 weeks respectively. NAD+-linked isocitric dehydrogenase activity continually increased with increasing testicular weight and age. It is suggested that during spermatogenesis the activities of these enzymes are controlled by different developmental mechanisms.