Mother-infant interaction; effects of sex of infant on feeding behaviour. Mother--child interaction was studied on the 2nd and 4th days after delivery. Mothers with girls showed more distal contact behaviour such as talking, smiling, and 'en face' responses. They also displayed more skin-to-skin contact behaviour (patting, rubbing, kissing, and touching) toward girl babies. Mothers with boys, on the other hand, showed more types of behaviours directed to clothed parts of the infant such as patting and adjusting clothes. These findings were statistically significant only on the 2nd day after delivery. On day 4 differences between male and female infants both in the frequency and in the pattern of sucking were observed.


The behaviour of infants whose mothers smoke in pregnancy. The Brazelton Neonatal Behavioural Assessment Scale was used to compare the behaviour patterns of infants of mothers who smoked during pregnancy and those whose mothers did not smoke. Smokers were mothers who had smoked more than 15 cigarettes/day throughout their pregnancy. Over a period of 9 mth, a total of 32 infants (15 of whose mothers smoked and 17 whose mothers did not smoke) between 4 and 6 days of age were examined and the results compared. The two groups were matched for maternal age, social class and parity. All infants were spontaneously delivered at term and of normal birthweight. Sex distribution was equal. Duration of labour and analgesia during labour were similar for smokers and non-smokers. Examinations were carried out in a warm, quiet semi-dark room, the examiner being unaware of which category the infant was in. There was evidence to suggest that the behavioural patterns of infants can be influenced by smoking in pregnancy and that in particular the auditory senses are affected.


The effect of maternal smoking on birth weight and the subsequent health of the child. The effect of maternal smoking during pregnancy on birth weight was studied in 12,068 births, the mothers in 1819 of which were regarded as smokers. The children of the smokers were compared with those of controls of similar age, parity, marital status and place of residence. Maternal smoking reduced birth weight in a dose-related manner. Birth weight was least affected among young, primiparous mothers who smoked only slightly, a difference which was, however, entirely caused by those mothers who stopped smoking for the last 3 mth of pregnancy, and this subgroup showed similar figures for postneonatal mortality and morbidity up to the age of 5 to those of their controls. Postneonatal mortality was higher in the total group of the smokers than among their controls, the primiparous or young mothers not differing in this respect from the others. Morbidity up to the age of 5 was significantly higher (p less than 0.001) among the children of the smokers, the children of the primiparas and young mothers being affected in a similar way to the others. The low birth weight infants of the smokers had a higher mean birth weight and lower perinatal mortality than the low birth weight infants of the controls, but morbidity up to age of 5 and postneonatal mortality were higher among the smokers in respect of both low birth weight infants and others.


Nutrition and early growth of preterm infants. Recent studies have renewed the controversy over what should constitute the best milk for preterm infants. While pooled human breast milk continues to be widely recommended it seems for reasons poorly understood not to allow adequate early post-natal growth. In view of possible programming of later growth and neuropsychological development by early nutritional experiences there is a need to further research the question of what should constitute optimum nutrition for preterm infants. We suggest that modifying or finding natural modifications in human milk rather than further altering cow's milk might provide some of the answers. Particular attention also needs to be given to long-term neurological, anthropometric and psychological assessment to relate functional outcome to early nutritional experiences.


Carbon 11 labeling of the psychoactive drug o-methyl-bufotenine and its distribution in the animal organism. A methylated derivative of serotonin, O-methyl-bufotenine has been labeled with 11C on the two methyl groups of the amine function. In order to avoid the cyclization which occurs during the Eschweiler-Clarke synthesis, we adopted a milder methylation procedure, based on Borch's method using [11C]formaldehyde and sodium cyanoborohydride. Several tens of millicuries of injectable product could be obtained in 50 min in a perfectly pure state and having a specific radioactivity of 50 to 100 mCi/mumol. The distribution study of O-methyl-bufotenine in the mouse and rabbit showed an accumulation of significant quantities of the compound in the brain, kidneys, lungs and liver. The study of the rapid kinetics of this hallucinogenic molecule is compatible with labeling by 11C, having a period of 20 min. The use of O-methyl-[11C]bufotenine to detect serotonin receptors in vivo in mental diseases, is considered.


The bedside determination of extravascular lung water: a non-invasive double indicator technique using 123I-antipyrine, 113mIn-transferrin and external counting. Using the formulae of Fazio and coworkers, we calculated the extravascular lung water per unit of blood volume (ELW/V) and per unit of blood flow (ELW/F) after intravenous injection of 113In-transferrin as the blood label, and 123I-antipyrine as the diffusible, i.e. water label. Time-activity curves were recorded over the right anterior upper chest wall using a mobile detector. The curves were digitalized and fitted to a gamma-variate using a GAMMA-11 computer. Area over height calculations gave the mean transit times (t). Sixteen control subjects, without evidence of cardiac or pulmonary disease, and 10 patients, with clinical and radiological evidence of left heart failure, were examined. In the control group ELW/V was 0.37 plus or minus 0.17 and ELW/F 3.39 plus or minus 1.56 (mean plus or minus 1 SD). In the patients ELW/V was 0.71 plus or minus 0.26 and ELW/F 13.10 plus or minus 5.67. The difference between both ELW/V and ELW/F for the control group and the patient group is statistically significant. Our values for ELW/V both in patients and control subjects are very similar to those obtained by Fazio and coworkers using H2 15O. However, our values for ELW/F differed from those of Fazio; this could be partly due to dependence of this parameter on the cardiac output.


A comparison of the structure and function of the terminal ileum in Crohn's disease using radiology, the "Dicopac" Schilling test and [14C] G.C.A. breath test. Twenty patients with Crohn's disease were studied. Thirteen had radiological evidence of involvement of the terminal ileum. None had significant bacterial overgrowth of the small bowel contents and none had had resection of the terminal ileum. In all patients a [14C] glycocholic acid ([14C] G.C.A.) breath test and a "Dicopac" Schilling test were performed to assess terminal ileal function. The data showed poor correlation between the radiological appearance of the terminal ileum and the results of the functional tests. There was also poor correlation between the results of the [14C] G.C.A. breath test and the "Dicopac" Schilling test. Without terminal ileal histology, any assessment of the extent of Crohn's disease of the terminal ileum and of its effect on terminal ileal function, must include the [14C] G.C.A. breath test as well as radiology and the "Dicopac" Schilling test. The limitations of the [14C] G.C.A. breath test as a test of terminal ileal function in Crohn's disease are discussed.


Computerized tomography and nuclear imaging of the liver: a comparative study in 83 cases. This study was performed to comparatively assess the diagnostic accuracy of computerized tomography (CT) and nuclear liver-scanning in detecting and defining circumscript and diffuse liver diseases in 83 patients. Presence or absence of liver diseases was assessed based on the results of invasive diagnostic procedures such as biopsy, laparoscopy, laparotomy, and/or autopsy. The percentage of true negative diagnoses was 94% for CT and 91% for static gamma-imaging (n = 33). With a rate of 94% true positive diagnoses, CT proved to be superior to gamma imaging with radiocolloids (81% true positives) in diagnosing circumscript liver diseases (n = 31). In addition. CT was superior to nuclear imaging regarding discrimination of number and size of space-occupying lesions within the liver. In contrast to nuclear screening, CT scans were pathognomonic to some circumscript liver diseases such as cysts, metastases, and perhaps echinococciasis. This was also true for obstructive jaundice. Nuclear imaging, because it reflects a sort of liver function, was superior with cirrhosis, whereas CT showed only alterations in the size and shape of the liver and spleen.


Experimental study on tumor affinity of 201T1-chloride. The tumor affinity of 201T1 was studied with normal and VX-2 cancer-bearing rabbits. 201T1 distribution in normal rabbit tissues was greatest in the kidney and heart muscle, followed by thyroid gland small intestine, spleen, lung, liver, bone marrow, bone, skeletal muscle, and blood, respectively. Accumulation into the thyroid varied greatly according to individuals. Generally, the taller the height of follicular cells, the greater was the affinity. Accumulation of 201T1 into the tumor transplanted into femoral muscle reached its maximum within 1 h after administration, and thereafter decreased gradually. When the tumor affinity was compared with that of 67Ga, the ratio of 67Ga accumulation to tissues (except blood) was greater than that of 201T1. Accumulation of 201T1 is significantly correlated to that of 42K, and the mechanism of 201T1-tumor affinity seems to be triggered by the acceleration of the potassium metabolism of a tumor. Accumulation into the inflammatory focus was greater with 67Ga as a ratio to muscle, while the ratio to blood was greater with 201T1.


99mTc-diethyl-HIDA: a contribution to the study of its structure. Sephadex column chromatography has shown that 99mTc-diethyl-HIDA consists of two clearly separable components. One of them seems to be an intermediate compound changing into the other, almost completely within two hours after reconstitution of the diethyl-HIDA (Solco HIDA) with pertechnetate. The two components could be the mono- and biscomplex of N-(2,6-diethyl-acetanilid)-imino diacetic acid with one atom of technetium. Animal experiments show that there is no important difference in the biological distribution in mice between the two components.


In vitro labeling of platelets with stable rubidium compounds. It is a common practice in diagnostic hematology to mark blood cells with radioactive tracers, such as 51Cr, 55Fe, 75Fe, etc., to determine their life-span and study their metabolism. A program has been started to verify the possibility of marking blood cells with stable indicators, assayed by radioisotope-induced X-ray fluorescence analysis. All elements may be considered as indicators aggregating to blood cells, and for in vivo measurements, which are not toxic in the quantities injected, calculated on the basis of the limit of detection of the technique. In this study platelets were marked with a very small quantity of stable compounds of rubidium, a potassium analog. Measurements were carried out in vitro on platelets of normal subjects and in vivo on platelets of rats and rabbits. Several survival curves were deduced and life-span values obtained in accord with previously reported values.


A chemical method for the labeling of fibrinogen with 99mTc. A new method allowing the labelling of fibrinogen with 99mTcO4- is described. The 99mTcO4- is reduced by stannous chloride in an alkaline medium. After 1 h incubation with fibrinogen, the pH was brought down to 7.1. The study of (1) the pH of the solution, (2) the quantity of the reducer, and (3) the time of incubation allowed us to specify optimal conditions for labeling. The labeling yield varied from 91.68% plus or minus 6.05% to 95.18% plus or minus 2.13% according to the method of control used: the precipitation of fibrinogen by (NH4)2SO4 25% or thin-layer chromatography with methylethylketone as solvent. Clottable radioactivity averaged 72% plus or minus 4.43%. Column chromatography separated the tracer into two radioactive peaks. The first peak corresponded to the fibrinogen and carried 73.36% plus or minus 5.8% of the total radioactivity. The total recovered radioactivity amounted to 89.86% plus or minus 8.07%. Spectroscopic clottability was 88.23% plus or minus 2.42%. The in vivo stability of the labeling and the molecule was followed for 24 h after intravenous injection. If the radioactivity measured in the 5 min sample was considered to equal 100%, the 24 h sample averaged 32.71% plus or minus 3.25%, of which 85.68% plus or minus 2.92% was recovered in the clot. In conclusion, this method enabled us to obtain a stable tracer that we used for routine investigations in man.


Heartburn in pregnancy.

Heartburn in pregnancy. It is assessed that heartburn with associated oesophagitis is experienced by 45% to 70% of pregnant women. Posture is the most constant associated factor; bile regurgitation through the pylorus is likely to be important in its aetiology but gastric acidity is not. Treatment with alkalis or dilute hydrochloric acid affords some relief in 95% of cases and patient acceptability is the most important factor in choice of preparation. Hiatus hernia is likely to be present in severe cases and rupture of the oseophagus has been reported. Early delivery may be advisable in the interest of the mother.


Some problems with antacids.

Some problems with antacids. The author points out that because a high intake of Vitamin D and calcium is normally encouraged in pregnancy, care should be taken in the prescription of certain antacids likely to cause alkalosis. Calcium-containing antacids are probably best avoided because of nocturnal acid rebound. Because of undesirable fluid retention in some situations in pregnancy caution should be exercised in the use of sodium-containing antacids. The very high sodium content of some antacids is stressed.


Gastro-oesophageal reflux in pregnancy: a review article. The author sets out a comprehensive review of gastro-oesophageal reflux in pregnancy. Comment is offered on the fairly limited means of treating this troublesome condition and some of the problems in future research are discussed.


The place of apomorphine prior to obstetric analgesia. The use of apomorphine is investigated as an alternative to the use of a stomach tube to empty the stomachs of patients in labour prior to the induction of general anaesthesia. Apomorphine was found to be much pleasanter for the patients, to be just as effective as a stomach tube and to have no deleterious effects on the infant.


The contribution of anaesthesia to maternal mortality. Anaesthesia is now an important cause of maternal death. Most deaths which occur in association with anaesthesia are preventable. Mendelson's syndrome and hypoxic cardiac arrest account for almost all maternal anaesthetic deaths. Although routine antacid therapy in labour does not guarantee to prevent Mendelson's syndrome, the use of antacids is nevertheless fully justified. There remains the possibility of pulmonary irritation due to food particles, bile salts and even the antacid itself. The role of difficult or failed tracheal intubation is emphasized in the causation of hypoxia and the pulmonary aspiration of stomach contents.


The measurement of gastric emptying during labour. The author describes how the rate of paracetamol absorption may be used as an indirect measure of gastric emptying rate in clinical situations such as during labour or post-partum, when direct measurement would be impracticable.


Gastric emptying in labour: some recent findings and their clinical significance. A résumé of the investigation of gastric emptying time in labour is presented with the results obtained recently in a series when the effects of narcotic analgesics, epidural analgesia, no analgesia and antagonistic drugs were studied. It is deduced that narcotic analgesics play a very large part in gastric delay in labour and epidural analgesia a comparatively small part. Some suggestions for future investigation and current management of the patient with delayed gastric emptying in labour are presented.


General practitioner management of gastroenterological problems in pregnancy. This paper discusses the problems of sickness and allied conditions in the pregnant patient, as dealt with by the general practitioner obstetrician who may use a General Practitioner Unit. Reference to basic physiology is made.


Chronic gastric ulcer and stress. A comparison of an ulcer population with a control population regarding stressful events over a lifetime. Stress was measured by the frequency of 31 major life events with consequent change and distress scores in 50 patients with chronic gastric ulcer and 50 control subjects, matched for age, sex and place of residence. The gastric ulcer population did not differ from the control population regarding the number of events experienced and the associated change and distress scores. However, when analysed according to social grade, the ulcer patients in the lower status suburbs experienced more events and more change than their controls, but the stress scores were similar. In the higher status suburbs, no difference was present between the patients and controls. Change and distress scores rose progressively with age, but there was no significant difference in the number of events experienced between the three age groups. Both men patients and their controls experienced significantly more events and higher change scores than women patients and their controls.


Age-dependent constitutional change in acidic glycosaminoglycans in human esophagus. The age-dependent constituents of esophageal acidic glycosaminoglycans (AGAG) were studied using 35 healthy individuals by electrophoretic characterization and enzymic assay with specific chondroitinases and hyaluronidase. Human esophageal AGAG comprised hyaluronic acid, dermatan sulfate, heparan sulfate and chondroitin 4- and 6-sulfate and oversulfated dermatan sulfate. Hyaluronic acid was the major part of AGAG at the young age but it decreased definitely with the advance of age. The proportion of dermatan sulfate and the oversulfated isomer to total AGAG significantly increased until adult age and then tended to somewhat decrease with increasing age. The proportion of heparan sulfate consistently increased with the advance of age.


Role of the ileocecal valve and site of intestinal resection in malabsorption after extensive small bowel resection. Intestinal absorption after extensive small bowel resections, for diseases other than Crohn's disease, was studied in 17 patients. When the ileocecal valve and the right colon were preserved, malabsorption was transient and moderate and had no prejudicial nutritional effect (fecal fat: 8.8 +/- 1.8 g/24 h in resections sparing the 2 distal bowel loops, and 16.2 +/- 4.8 g/24 h in resections including the distal ileum; mean +/- SEM). When colectomy was associated, malabsorption was severe and persistent (fecal fat: 47.4 +/- 12.2 g/24 h; mean +/- SEM). These findings suggest that the most important prognostic factor in extensive small bowel resection is the site of the resection, and particularly the presence or absence of the right colon and ileocecal valve.


Multicenter survey of the etiology of pancreatic diseases. Relationship between the relative risk of developing chronic pancreaitis and alcohol, protein and lipid consumption. The relationship between the average daily intake of alcohol and the risk of developing chronic pancreatitis was studied in two surveys, one in Marseille (France), the other in 9 centers, in Caucasian-populated countries. In the latter survey, the interactions between alcohol, protein and fat consumption and the risk of chronic pancreatitis have also been statistically analyzed. These studies were performed with hierarchical log-linear models for contingency tables, the relative odds being taken as an approximation of the relative risk. It has been shown that there is no apparent threshold of toxicity of alcohol on the human pancreas. The logarithm of the relative risk of chronic pancreatitis increases linearly as a function of the quantity of alcohol and protein consumed, and varies quadratically as a function of average daily lipid intake (a low- or high-lipid diet increases the risk of developing chronic pancreatitis in comparison to an average-fat diet (85--110 g fat per day). The effects on log-relative risk of alcohol, fat and protein daily consumption are additive. In Marseille, the average duration of alcohol consumption before the appearance of symptoms is 18 +/- 11 years for males and 11 +/- 8 years for females, which is much shorter than the duration of alcohol consumption before onset of symptoms in cirrhotic patients.


Inhibition of exocrine pancreatic secretion by somatostatin in dogs. The effect of somatostatin on the pancreatic exocrine response to different doses of exogenous stimuli and the somatostatin dose-response relationships on pancreatic secretion were studied in conscious dogs. Somatostatin caused a strong inhibition of basal or slightly stimulated pancreatic secretion but failed to inhibit the maximal responses, suggesting that somatostatin interacts with secretin or caerulein by a competitive mechanism. A higher maximal percentage of inhibition and a dose-response relationship was observed with protein outputs and enzyme concentrations. Volumes and bicarbonate outputs were also inhibited but the maximal percentage of inhibition was lower.


Proteolytic proenzymes in the pancreas in the course of experimental bile-induced pancreatitis in the guinea pig. The levels of the proenzymes trypsinogen and chymotrypsinogen were studied in guinea pigs with pancreatitis induced by injection of sodium taurocholate containing the antibiotic cephalothin. This treatment inhibited the enzyme activities and prolonged the activation times of the proenzymes. Both trypsinogen and chymotrypsinogen content decreased after induction of pancreatitis, but there were no significant changes in the proenzyme contents in relation to injection-to-excision times. Sodium taurocholate and cephalothin were cleared from the pancreas in 2 h. Administration of chlorophyll-a together with the inducer caused a slight increase in proenzyme levels.


Influence of biliary stasis on enterokinase activity in the rat. After 48 h of bile duct ligation, enterokinase activity in rat mucosa was significantly lowered in comparison with controls or rats with bile fistula. Rats with bile fistula were similar to controls. Sucrase levels were similar in all groups. Without endogenous trypsinogen, duodenal perfusion with a trypsinogen-containing solution led to more conversion to trypsin by controls. When their own pancreatic secretion was the source of trypsinogen, trypsin was much higher in perfusate from bile-ligated rats. Solubilized enterokinase was also higher in this group. These results indicate that bile stasis leads to decreased mucosal enterokinase activity and increased pancreatic function. The latter may have caused accelerated loss of enterokinase into the lumen, leading to lower mucosal levels.


Effect of cimetidine on tritiated thymidine incorporation by the stomach, jejunum, colon, liver and spleen of mice. The administration of cimetidine to mice at a dose of 200 mg/kg and per 24 h inhibits the tritiated thymidine incorporation by the stomach, jejunum, colon and liver and stimulates incorporation by the spleen. These results may furnish an explanation for the rare secondary effects observed in humans. It is also proposed that endogenous histamine may play a role of cytohormone, regulating tissue trophicity.


Reprogramming and DNA synthesis in Galleria mellonella larval epidermal cells. Epidermal cells from ligated day-3 last instar larvae of Galleria mellonella secrete a larval cuticle if exposed to ecdysone immediately following ligation; whereas, they deposit a pupal cuticle if exposed to ecdysone three to four days after ligation. During the period of reprogramming the genome in the diploid cells of the wax moth larvae no DNA synthesis occurs. This is direct proof that DNA synthesis is not required for reprogramming in the epidermis of Galleria during larval-pupal transformation.


Postfertilization poly(A) . protein complex formation on sea urchin maternal messenger RNA. A two-fold increase in polyadenylate [poly(A)] content occurs between fertilization and the two-cell stage in sea urchin zygotes. In this report the role of this cytoplasmic polyadenylation process in the provision of binding sites for poly(A)-associated proteins during early development of Lytechinus pictus is evaluated. Protein-associated poly(A) sequences, from ribonuclease-treated, post-mitochondrial supernatants of various developmental stages, were collected by nitrocellulose filtration and quantified by 3H-poly(U) complex formation. The proportion of protein-associated poly(A) rose from about 27% to about 60% of the total poly(A), on a nucleotide basis, during the period between fertilization and the eight-cell stage. However, the actual increase in number of poly(A) sequences associated with protein was more extensive, about 2.5-fold, since protein-associated poly(A) sequences average about 45 nucleotides longer than free poly(A). The protein-associated poly(A) of eggs and zygotes is found in two types of protease-sensitive complexes which sediment at 8--12 S and 15--20 S. The 8--12 S complex appears to be selectively increased in amount following fertilization. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the poly(A) protein complex fraction indicates the presence of 87,000 and 130,000 molecular weight polypeptides in both eggs and zygotes. It is concluded that quantitative, but not qualitative, alterations in the proportion of protein-associated poly(A) accompanies post-fertilization cytoplasmic polyadenylation in sea urchin zygotes. The attachment of specific proteins to the 3' terminus of maternal RNA's may be involved in their subsequent activities during early embryogenesis.


Tubercidin metabolism in mouse L5178y cells in vivo and in vitro. Tubercidin (7-deazaadenosine) is a strong inhibitor of cell proliferation in mouse L5178y cells. Radioactive tubercidin is incorporated into DNA and RNA. Poly(A)-containing RNA shows the highest specific radioactivity. The amount of low molecular weight 4S and 5S RNA is diminished to some extent under the influence of the compound. Tubercidin triphosphate is a potent inhibitor of DNA-dependent DNA polymerases alpha and beta, and the DNA-dependent RNA polymerases I, II, and III, although the efficiency of its incorporation is lower than of dATP and ATP. Tubercidin triphosphate also seems to be a good substrate for the Mg2+-dependent poly(A) polymerase.


Microsomal enzymes in patients with gastric carcinoma as determined by plasma half-life of antipyrine. Metabolism of antipyrine was studied in 12 patients with gastric carcinoma and 5 control subjects with peptic ulcer matched for sex, body weight, height, and smoking history. The mean antipyrine half-life was significantly longer (21.5 +/- 1.5 hr) in 3 patients with disseminated gastric carcinoma compared to control subjects (9.3 +/- 1.5 hr) (P less than 0.001). There was no significant difference in the mean antipyrine half-life between 9 patients with localized gastric carcinoma and control subjects. Similarily, the mean metabolic clearance rate of antipyrine was significantly lower (22.8 +/- 5.0 ml/hr/kg) in patients with disseminated gastric carcinoma compared to control subjects (52.6 +/- 13.4 ml/hr/kg) (P less than 0.02). Thus, the presence of gastric carcinoma in humans might alter antipyrine elimination. Significant negative correlation was observed between antipyrine half-life and albumin concentration (r = -0.786, P less than 0.01). These observations indicate that the decrease in antipyrine half-life is not primarily due to the presence of tumor but rather to the nutritional status of an individual.


Effect of azathiopurine and OK-432 on urinary bladder carcinogenesis in rats. The effect of azathiopurine and OK-432 on bladder carcinogenesis in rats was evaluated using the carcinogens, N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) and N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT). Azathiopurine did not affect FANFT bladder carcinogenesis in any treatment. By contrast, when azathiopurine was fed simultaneously with BBN there was a significant increase in the incidence of bladder tumors, although it had no effect if administered before or after BBN. Short-term administration (8 weeks) of OK-432 subcutaneously before, during, or after BBN did not affect bladder carcinogenesis, but if OK-432 was begun after BBN and continued until the end of the experiment, the incidence of BBN-induced bladder tumor was significantly reduced. No bladder lesions were observed in control rats or in rats receiving only azathiopurine or OK-432.


Tumor induction in the glandular stomach of rats after oral administration of a single or a few doses of N-methyl-N'-nitro-N-nitrosoguanidine during the newborn period. When N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was orally intubated to conventional newborn rats by the catheter technique, the rats were found with tumors almost exclusively developed in the glandular stomach, mostly until 280 days after the first intubation. Tumor incidence was about 50% in both sexs of rats that survived the intubation of a single dose of MNNG in rats of less than 24 hr after birth and almost 100% in both sexes of rats that survived the intubation of three consecutive daily doses of MNNG on 5th day after birth. Out of 52 rats treated with MNNG, 40.4% developed carcinomas (20 adenocarcinomas and 1 squamous cell carcinoma), three of them having metastatic lesions. The predilective localization of tumors in the glandular, especially fundic, portion of the stomach, might be attributed to the use of newborns and to the catheter technique devised here.


Effect of BCG cell-wall skeleton immunotherapy on the peripheral blood lymphocytes in patients with lung cancer after radiotherapy. The effect of radiotherapy on peripheral blood lymphocytes (PBL) of lung cancer and the effect of BCG cell-wall skeleton (BCG-CWS) on recovery of impaired PBL were examined. A remarkable depression of the absolute number of E- or EAC-rosette cells and of the response of PBL to mitogens were observed immediately after radiotherapy, and these continued for several months. With BCG-CWS immunotherapy, the response of PBL to phytohemagglutinin recovered rapidly, compared with non-vaccinated patients. The response of PBL to pokeweed mitogen seemed to give similar results. These results suggested that BCG-CWS injection to the patient receiving radiotherapy was effective for recovery of T-cell response.


Antitumor activity of prolonged-release derivative of cytosine arabinoside, cytosine arabinoside-agarose conjugate. A prolonged-release derivative of cytosine arabinoside (Ara-C), cytosine arabinoside-agarose bead conjugate (Ara-C-AB), was synthesized and its pharmaceutical and pharmacological characteristics were examined. Ara-C was released successively for considerably long period from Ara-C-AB in vitro. Following intraperitoneal injection of 3H-Ara-C-AB, radioactivity could be detected in plasma and urine of BDF1 mouse for four days, while 3H-Ara-C administered as a free form was excreted completely in the first 24 hr. Increase in lifespan of L1210 leukemia-bearing mice was demonstrated after intraperitoneal injection of Ara-C-AB with both the dosage schedules of three days before and one day after inoculation of L1210 cells at the dose of 30 mg equivalent Ara-C/kg.


Effect of vitamin A acetate on urinary bladder carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine in rats. The effect of vitamin A acetate on the urinary bladder carcinogenicity of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was determined in male Wistar rats. Vitamin A acetate at the dose administered induced no changes in the urinary bladder or other organs when administered without the carcinogen. However, hypervitaminosis A inhibited keratinization and squamous metaplasia in bladder lesions induced by BBN, and the incidence of transitional cell carcinoma and papilloma of the urinary bladder was significantly reduced at a dose greater than 100 IU/g diet (P less than 0.02). The present experiment suggests that for the urinary bladder epithelium of rats hypervitaminosis A reduced susceptibility to the tumorigenicity of BBN.


Canine kidney cells: III. Neutral lipids, phospholipids and fatty acids of primary canine kidney cells in monolayer culture. Neutral lipids, phospholipids and fatty acids were studied in monolayer grown primary canine kidney whole cells and their plasma membranes which were isolated by the Warren fluorescein-mercuric acetate technique. Triglyceride and unesterified cholesterol were the predominant neutral lipids of whole cells, while cholesterol ester, free fatty acid, and unesterified cholesterol were the major neutral lipids of plasma membranes. The total neutral lipid value is about 2-fold greater in plasma membranes than in whole cells. Phosphatidyl ethanolamine and physophatidyl choline are the major phospholipids of whole cells and plasma membranes. The total phospholipid value is almost 1.8-fold greater in plasma membranes than in whole cells. The fatty acid profiles of both whole cells and plasma membranes differ from that of calf serum used in the growth medium. The amount of unsaturated fatty acids is considerably lower while the amount of saturated fatty acids is higher than the corresponding values obtained in calf serum.


Allometry and multivariate growth.

Allometry and multivariate growth. Multivariate allometry, and conservative and nonconservative growth models are generalized by a set of global differential equations, preserving the linear trajectory property. Linear least squares methods are exposited for estimation of parameters, comparing special cases and drawing qualitative conclusions. Three classical sets of data are analyzed in detail, illustrating the usefulness and simplicity of the method.


The net weight of the rat liver.

The net weight of the rat liver. Contribution of blood to the post-mortem weight of the liver was measured by an isotopic technique in 269 rats with body weights ranging from 110 g to 480 g. Amounts of blood in the liver increased proportionately to the body and liver weights so that the portion of gross organ weight attributable to blood remained constant at 16.9-17.9%. Examination of the liver weight: whole body weight relationship for both gross and net liver weights by the conventional equation, Y = aXb, indicates that trapped blood affects exponent b very little but it alters coefficient a.


Longissimus muscle and plasma enzymes and metabolites in fetally decapitated pigs. Fetuses of nine gilts were decapitated (D) in utero and fetuses of eight gilts were sham operated (C) at 43 to 47 days of pregnancy. At 110 days, one fetus from each gilt was studied. Heart, liver, kidney, thyroid and body weights were recorded. Thyroids were evaluated for the degree of colloid accumulation and height of the follicular epithelium. Blood glucose, lactate, triglycerides and creatine phosphokinase activity were determined. Longissimus muscle glycogen was evaluated histochemically. Longissimus muscle total phosphorylase, phosphorylase a, G-6-PDH and SDH activity and glycogen were determined biochemically. The D fetuses were hairless, edematous, devoid of adrenal glands and unaffected by maternal anesthesia. Results indicate that the fetal pig pituitary gland is not required for continued fetal growth, but is necessary for normal organ and endocrine gland development. Fetal decapitation caused delayed maturation of the longissimus muscle with little change in anaerobic glycolytic capacity but decreased aerobic glycolytic capacity accompanied by increased activity of the pentose shunt.


The effects of lipectomy on remaining adipose tissue depots in the Sprague Dawley rat. Adult male castrate Sprague Dawley rats were subjected to surgical removal of the right inguinal and both epididymal fat depots. Lipectomized rats were not significantly different from controls in total body fat at approximately 13 weeks after surgery suggesting a compensatory fat gain in response to the lipectomy. Mean wet weight of the major individual fat depots dissected from lipectomized rats exceeded those of the control rats with the exception of surgically excised depots. The generalized trend for the adipose tissue mass to compensate in response to lipectomy was in part due to a partial regeneration of the excised inguinal fat depot. It was observed that the cellular nature of the fat compensation was dependent on the location of the tissue. The major internal depots compensated by a significant increase in average fat cell size, whereas the major subcutaneous depot (inguinal) compensated by a significant increase in the apparent fat cell number with no change in cell size.


Size and shape of Kedah-Kelantan cows.

Size and shape of Kedah-Kelantan cows. Body weight and nine body measurements were recorded on 79 mature Kedah-Kelantan cows at two locations. The Kedah-Kelantan is an indigenous cattle of Malaysia. A principal component analysis was used to study size and shape as indicated by the dependence structure among measurements. The total variation among measurements associated with the first principal component which was interpreted as a measure of general size was 40.8%. The second principal component contrasted cows tall at the withers, and deep at the chest with top line sloping downward and under line sloping upward from front to rear with those having less wither height and chest depth and straighter lines. This contrast accounted for 14.3% of the variation in body dimensions. The third principal component contrasted long, narrow, and deeper cows with a more compact type. This contrast accounted for 10.7% of the variation in body dimensions.


Hormonal influences on the growth and enzymic differentiation of the small intestine of the hypophysectomized rat. When rats are hypophysectomized in neonatal life, the growth of the small intestine is more severely retarded than the growth of the body as a whole. It was shown previously that intestinal growth is not rectified by doses of cortisone and/or throxine that restore normal activity of brush border enzymes in hypophysectomized sucklings; growth hormone did not affect relative weight or enzyme activity. Reexamination of this problem with much lower doses of hormones than previously employed has now shown that relative weight of the intestine is enhanced by cortisone and thyroxine together, and is normalized by cortisone and thyroxine in combination with rat growth hormone. Growth induced by treatment with the three hormones involved increases of crypt depth and villus height, and of mitotic index. Body weight was not affected by hormonal treatment, but the tails of the hypophysectomized sucklings were significantly lengthened by thyroxine alone, the effect being enhanced when growth hormone was also given. The physiological dose of hormones used in the present study were as effective in elevating activity of alkaline phosphatase and sucrase as the larger doses previously used. Cortisone had a greater effect on sucrase, thyroxine on phosphatase. Pentagastrin did not influence either growth or enzyme activity.


Plasma concentrations of chloroquinaldol (Sterosan) after administration of a vaginal tablet. The systemic absorption and the plasma concentrations of chloroquinaldol have been determined after local application of one vaginal tablet of Sterosan. A peak plasma concentration of 33 ng/ml was determined 12 h after application. A mean absorption of 6.0% of the applied dose was estimated.


Antihypertensive treatment with the adrenergic beta-receptor blocker metoprolol during pregnancy. In 101 hypertensive gravidae the selective beta-blocking agent metoprolol alone or in combination with hydralazine has been used. The effects of the mother and fetus have been compared with those of 97 hypertensive gravidae treated with hydralazine. In both groups a small dose of a thiazide was added. Perinatal mortality was lower in the metoprolol group (2.0%) than in the hydralazine group (8.0%). The rate of fetal growth retardations also was lower when using metoprolol (11.7 and 16.3% respectively). No abnormal effects of the beta-blocker was noticed on the fetus.


Influence of long-term beta-mimetic therapy on the lecithin content of amniotic fluid. The lecithin content of 157 amniotic fluid samples taken from 60 patients who had been treated with Fenoterol over a long period of time (longer than 30 mg/daily per os for 14 days; intravenous infusion for longer than 7 days) was calculated thin-layer chromatographically according to Kynast and Saling. These lecithin levels were statistically compared with the levels in a control (Wilcoxon test). It emerged that the lecithin levels in the long-term beta-mimetic therapy group were significantly lower, i.e., from 33/0 to 39/6 (33/0-34/6, p less than 0.05; 35/0-39/6, p less than 0.01). The answer to the question how often levels occur in the long-term group which are below the as critical described level of 3 mg Lec/100 ml amniotic fluid appears to be clinically important. It is shown that values below the critical level from 33/0 to 39/6 are much more frequent in the long-term beta-mimetics therapy group than in the control group. There is no known explanation for this. It was concluded that the application of beta-mimetics in cases of long-term tocolysis should only be discontinued when the lecithin content of the amniotic fluid lies above the critical limit of 3 mg Lec/100 ml.


[Studies on the anti-ulcer effects of isoprenyl flavonoids (1). The anti-ulcer effects of isoprenyl chalcone extracted from Sophora subprostrata (author's transl)]. A series of extracted fractions from sophora subprostrata was screened by determining anti-ulcer effects in pylorus ligated and stressed rats. Fr. [C-2] had the most potent anti-ulcer effects of all fractions extracted. Sophoradin and sophoranone which were isolated from Fr. [C-2] were also found to have inhibitory effects on ulcer formation in pylorus ligated and stressed rats. The anti-ulcer effect of sophoradin was relatively potent in comparison with that of sophoranone and/or Fr. [C-2]. The anti-ulcer effect of sophoranone was approximately the same as that of Fr. [C-2]. The authors examined the effects of sophoradin and sophoranone on gastric secretion in pylorus ligated rats. Sophoradin and sophoranone significantly reduced the volume of gastric juice. Sophoradin but not sophoranone inhibited the free and total acid output of gastric juice. The effect of sophoradin was examined on various secretagogues which induced gastric secretions in rats with acute fistula. Sophoradin showed a tendency to inhibit tetragastrin- and insulin-induced gastric acid secretion, but there were no effects on methacholine- and histamine-induced secretions. These results suggest that sophoradin may have marked anti-ulcer and inhibitory effects on gastric secretion.


[Research on the contracting and relaxant actions of cardiac steroids on the taenia coli of guinea pig (author's transl)]. Actions of cardiac steroid (CS) such as bufadienolides and cardenolides, on guinea pig taenia coli were studied using the double sucrose-gap method. When an appropriate dose of CS was applied, the taenia coli first contracted, then relaxed. After removal of CS, the relaxation was enhanced and continued for 20-40 min. In decreasing order of the relaxant action were bufalin, ouabain, cinobufagin and resibufogenin. Further application of CS after occurrence of the relaxation induced a secondary gradual contraction. The contraction occurred with the membrane depolarization and increase in spike discharge, and the relaxation corresponded fairly well with decrease in spike discharge and the membrane repolarization. Membrane resistance was decreased during the contraction as well as the relaxation. The decrease in membrane resistance continued during the relaxation after removal of CS, Na, K and Ga conductances were increased by CS application, respectively. The increase of Na conductance was relatively high during the contraction, and the increase of K conductance was remarkable during the relaxation and after removal of CS. From the foregoing results it is considered that the contracting action is due to inhibition of the Na pump and that the relaxant action is due to the change in electrical properties of membrane produced by a marked increase in intracellular Na and the increase of K permeability. The relaxation after removal of CS is considered to be due to the activated electrogenic Na pump as indicated from the changes in electrical properties of membrane.


[Changes in cholinesterase activity of gastrocnemius and soleus muscles of the rat after crush of the sciatic nerve, and effects of a vitamin B complex on those changes (author's transl)]. In an analysis of the gastrocnemius muscle, the microsomal fraction showed the highest cholinesterase (ChE) activity. The ChE activity of all fractions decreased to a greater extent after strong nerve crushing than after weak crushing. This change in the activity in the microsomal fraction was the most marked change observed. Although in the analysis of the soleus muscle the ChE activity was measured only in the homogenate and in the microsomal fraction, the results were the same as those obtained with the gastrocnemius. A preparation of vitamins B1, B2, and B12 (B complex) had little effect on the ChE activity in the gastrocnemius muscle. In the soleus muscle on the lesion side, the B complex increased the ChE activity to some extent after nerve crushing, but such was not significant. However, the B complex signifiicantly increased this activity in the soleus on the intact side. In the soleus muscle, strong nerve crushing induced more marked muscle atrophy than weak crushing. On the other hand, no significant difference was found in the gastrocnemius. Effects of the B complex on muscle atrophy were found in the soleus, but not in the gastrocnemius. These results suggest that the ChE activity in the microsomal fraction containing sarcoplasmic reticulum reflects the nervous disorders clearly, and that the B complex increases the ChE activity and muscle weight in the soleus, but not in the gastrocnemius muscle.


[Studies on circadian susceptibility rhythm to haloperidol (author's transl)]. Rats were given haloperidol in a variety of doses and time combinations and the sedation period were then measured. A clear-cut daily fluctuation in the sedative effect was observed, and the pattern of fluctuation differed depending on the dosage. In an attempt to elucidate the mechanism of this phenomenon, haloperidol was administered at two different times between which there was a significant difference in the sedation period. No difference was found. Thus it is presumed that daily fluctuation in the sedative effect of haloperidol may be ascribed not to the daily fluctuation in the levels of absorption, excretion, metabolism, or distribution of this drug, but rather to the daily fluctuation at the level of catecholamine receptors in the brain. There was a daily fluctuation in the antiapomorphine effect of haloperidol in a variety of doses and time combinations, and the pattern of fluctuation almost equaled that of the sedative effects of haloperidol. The daily fluctuation of the sedative effect is probably due to effects of circadian rhythm in brain dopamine receptors.


[Psychopharmacological effects of flutazolam (MS-4101) (author's transl)]. Behavioral effects of Flutazolam (MS-4101), a new derivative of benzodiazepines, was investigated and compared with effects of diazepam in mice and rats. MS-4101 suppressed hyperemotionality in septal rats, fighting behavior in long-term isolated mice and pentylenetetrazol convulsion and potentiated thiopental sleep. These effects of MS-4101 were the same in potency as those of diazepam. MS-4101 was more potent than diazepam in reducing the spontaneous locomotor activity in the open-field test and potentiating the stimulant effect of methamphetamine on locomotor activity. On the other hand, suppression of hyperemotionality in O. B. rats, potentiation of ethanol-induced anesthesia, prevention of maximal electroshock, prevention of strychnine convulsin and muscle relaxant effect of MS-4101 were less potent than in the case of diazepam. MS-4101 had also an anticonflict effect, which was less potent than that seen with diazepam. Suppression of locomotor activity was potentiated by chronic administration of MS-4101, but disappeared with chronic administration of diazepam. MS-4101 inhibited considerably both scratching and head-twitch induced by mescaline in mice. Scratching was increased with small doses of diazepam and decreased with high doses. Head-twitch was decreased with small doses of diazepam and increased with high doses.


[Effect of oxythiamine and pyrithiamine on rat brain--morphological changes in the thiamine deficient rat brain (author's transl)]. We observed under light and electron microscopes morphological changes in the brains of rats in a thiamine deficient state as induced by an oxythiamine, pyrithiamine and thiamine deficient diet (OT, PT and TDD). We simultaneously determined thiamine levels in the whole brain of rats. The rats were separated into six groups-normal control, OT or PT treated rats (OT or PT group), OT or PT treated rats fed a TDD (OTD or PTD group), rats fed a TDD (TDD group)-. Microscopically, there were symmetrically distributed lesions containing spongy reticulation mainly in the vestibular nucleus. Electron microscopically, we found more advanced lesions in the OTD and PTD groups than in the TDD group. These ultrastructural changes were seen in the vicinity of capillaries and such consisted of abnormal endothelial cells and pericytes, excrescence of microglias, swelling or vacuolation of astrocytes, nerve cells containing distorted organelle and myelin degeneration, besides extracellular edema. The thiamine level in the TDD group decreased to 56% that of control. No effect of OT on the thiamine level was observed either in case of ingestion of a regular diet or when TDD was given. On the other hand, the thiamine level decreased to 43% in the PT group and to 17-23 in PTD. These results suggest that encephalopathy caused by the OT or PT-induced thiamine deficiency has the same selective vulnerable site as does the TDD-induced deficiency, however cellular sensitivity may differ slightly with the various ultrastructural changes.


On early and mid-adolescent schizophrenia.--Part II: prognosis, course and defect. Twenty-three adolescent schizophrenics were studied in regard to the problems of the course of illness, prognosis and defect. Illustrations of cases (follow-up for three to 15 years) were presented. 1) The course was considered chiefly from the viewpoint of positive symptoms, namely paranoid-hallucinatory experiences. It was divided into the following four categories; remittent, persistent, scanty and fading types. At the same time, general characteristics of each type were discussed. 2) As to the changes in clinical forms, hebephrenia was gradually manifested in more than half of the cases. There were some cases in which the expansion of paranoid activities were observed. These two prominent tendencies might be explained in terms of personality disintegration and maturation. We were impressed, in this regard, that autistic tendencies and behavior disturbances were more manifest in the initial stages in patients who later turned more hebephrenic. 3) A mild defect was observed in fourteen cases, while a medium or severe defect was recognized in eight cases. Generally, the degree of defect seemed to be more manifest in female patients than in males. Moreover, the defect was generally more severe in early adolescent cases and in patients with insidious onsets as well as in those with a longer duration of illness than in mid-adolescent patients and those with acute onsets and a shorter duration of illness. 4) As the result of this investigation, it was substantiated that the prognosis in adolescent schizophrenia, especially in early adolescence, was unfavorable. 5) Finally, we were impressed by the fact that there were many patients who were treated mainly in ambulatory clinics or who stayed at home in spite of the above-mentioned unfavorable prognosis.


The effects of sleep deprivation on the circadian rhythm of plasma cortisol levels in depressive patients. The circadian rhythm of plasma cortisol levels was studied in 20 endogenous depressive patients who received one-night sleep deprivation therapy and 10 normal controls who were also deprived of sleep together with patients by estimation at four-hourly intervals over 36 hours. The mean values at each sampling time were compared. The result can be summarized as follows: The mean values of depressive patients tended to be higher than those of controls on the day following sleep deprivation. In depressive patients the mean values on the following day were higher compared to those on the preceding day. In the patients who responded well to sleep deprivation therapy, the circadian variation of mean values which was obscure the preceding day showed an evident rhythm the following day. These findings suggest that sleep deprivation may cause a different effect between depressive patients and normal subjects, and that the possible mechanism of the anti-depressive efficacy of sleep deprivation may be to normalize the disturbed rhythm of the physiological function in depressive patients.


Unusual case of presenile dementia.

Unusual case of presenile dementia. A 63-year-old woman showed the dominant clinical features of aphasia as the initial symptom in the course of presenile progressive dementia. Computerized axial tomography showed strikingly dilated Sylvian fissures, particularly in its posterior aspect, in the presence of moderate diffuse cortical atrophy. EEG revealed a slowdown in activity with the dominance in the left fronto-temporal area. The radiographic and EEG findings correlated well with the clinical data. This case was compared with those of presenile dementia previously reported. This is a unique case report of presenile dementia.


Anxiety symptoms of the patients with aortic arch syndrome. We reported six cases of the aortic arch syndrome with brain symptoms. Two could be explained directly as an organic impairment of the brain. In the remaining four cases, however, the mental symptoms were considered to have a basis of "anxiety."  They were easily precipitated by iatrogenic and other various environmental factors. The hyperventilation syndrome had a high incidence occurring in three out of the four cases of anxiety. Thus, it seems appropriate to interpret their symptoms psychosomatically. The production of brain symptoms may be due to psychosomatic mechanisms in many cases of the aortic arch syndrome.


On so-called atypical psychosis in early and mid-adolescence. Twenty-three cases of adolescent atypical psychosis were reported, of which 12 were followed for more than three years (at the longest about 18 years). Our cases indicated apparent atypicalness in regard to the symptomatology and to the course, quite different from cyclothymic psychosis and schizophrenia. In an etiological point of view, hereditary predispositions were more frequently recognized in our cases than in schizophrenic cases, but because schizophrenics were found in the families of these patients, it was difficult for us to determine whether our cases belonged to an etiologically independent endogenous psychosis. However, we received the impression that atypical psychosis could be differentiated from others even in adolescents. But this psychosis was seldom found in childhood. While, through the comparison of these patients with adult cases and by considering previous research, we were led to the assumption that adolescent atypical psychosis might be understood as a minor pattern of the fully-developed psychosis in adults but was provided with many properties specific to adolescense.


The property of contingent negative variation (CNV) in psychiatric patients: schizophrenia and neurosis. The CNV parameters (amplitude and morphology) and the relationship between CNV parameters and performances (motor response time) were studied on schizophrenics (15 subjects), neurotics (15 subjects) and normal controls (30 subjects divided into 2 groups) in order to clarify the property of CNV in psychiatric patients. Also, the relationship between CNV and personality traits was investigated in neurotics. Since it has been known that age, sex and psychoactive drugs influence the CNV genesis in normal subjects, the control group method was used for these factors in this study. The results obtained were as follows: 1) Mean amplitudes of CNV's for schizophrenics and neurotics in each session of control, nonresponse and recovery tended to be lower than those for normal controls. Significant differences were found between schizophrenics and normal controls. 2) Correlations between CNV amplitude and response time in schizophrenics tended to be positive, while normal controls showed significantly high negative correlations. These findings were discussed from the viewpoint of the arousal theory of CNV genesis. 3) For the neurotic patients, the personality variables appeared to influence CNV amplitude. 4) Type B-CNV was most frequently seen in all sessions for normal controls. Schizophrenics and neurotics tended to show the increment of type P-CNV in nonresponse sessions without a motor response. 5) "Field Dependency" type-CNV was not found in psychiatric patients. This result did not correspond with the data reported by other investigators. 6) Type III- and type IV-prolonged CNV's appeared almost especially in schizophrenics although type II-CNV was observed in all groups. The mechanism of genesis of the prolonged CNV's was discussed.


Dissociation of visual and auditory language comprehension capacity in aphasia. Visual language comprehension capacity was compared with auditory language comprehension capacity in 26 aphasic subjects. The Token Test was used for both modalities. By the means of the difference in scores on the two tests three groups were separated, that is (1) a group with no essential difference between the two capacities, (2) a group with superior reading capacity and (3) a group with superior auditory capacity. Particular attention was directed to the second group. Seven subjects showed this type of dissociated comprehension. The group was found to be heterogeneous in their linguistic characteristics. The clinical type of aphasia included not only Wernicke's aphasia but also Broca's aphasia. A possible psychological explanation underlying this phenomenon was attempted. Anatomical correlation was also attempted. The hypothesis of sparing the left inferior parietal lobe is proposed as an explanation of why visual comprehension was better preserved than auditory comprehension.


Further studies of effects of chlorpromazine on the contingent negative variation. The effect of 25 mg of chlorpromazine (CPZ) on the contingent negative variation (CNV) at Cz and Oz was studied in nine male subjects. Two kinds of warning stimulus (S1)--imperative stimulus--and motor response (MR) were used. A click as S1 was common to both, while either flashes or electrical stimulation was used as S2. Simultaneously with CNV recording, the reaction time of the finger movement as MR to S2 was measured in five of nine subjects. The results obtained were as follows. 1) CNV amplitudes after CPZ administration were decreased significantly both at Cz and Oz when S2 was flashes and only at Cz when S2 was electrical stimulation. 2) Significant positive correlations of CNV amplitudes between Cz and Oz were found both before and after the drug administration. 3) Reaction times to flashes and electrical stimulation as S2 were not affected by CPZ administration. 4) The reaction time to flashes was significantly shorter than that to electrical stimulation irrespective of pre- and post-administration of CPZ.


Pontine infarction with diffuse myelin destruction. A 57-year-old man with clinical symptoms of dementia and spastic paraplegia revealed pathologically scattered cerebral arteriosclerotic changes and diffuse myelin destruction in the basis pontis. The latter was characterized by comcomitances with an eminent fibrous gliosis and a neuronal as well as an axonal loss. Pontine infarction and the following fibrous gliosis possibly caused a wide area of myelin destruction resembling cpm.


The structural events associated with the attachment of complement components to cell membranes in reactive lysis. Electron microscopic study of the events occurring at the cell membrane during reactive lysis by complement, showed that a foliaceous particle was formed at the C5b-7 stage, that enlarged to a particle with a variable number of arms at the C5b-8 stage. Up to this point, no typical complement lesions were found. At the C5b-9 stages, the particles were completely converted to typical complement lesions, i.e. hollow cylinders projecting from the cell membrane and partly penetrating it. C5b-9 complexes assembled in the fluid phase did not show the typical structure of the lesions, but were amorphous masses of fibres.


Studies on the immune protection to murine experimental brucellosis conferred by Brucella fractions. I. Positive role of immune serum. Mouse inoculation with three different phenol-insoluble fractions extracted from Brucella melitensis (fractions 'PI', '4A' and '5') induces an acceleration of the blood clearance of i.v. inoculated live Brucella and a diminution of the rate of multiplication of the injected bacteria in the spleen. Preincubation of the challenge inoculum in immune serum or i.p. injections of immune serum confer a good specific protection to non-immunized hosts. The results observed with fractionated sera suggest that, not only antibodies, but also other serum constituents may participate in the protective activity of immune sera. This discussed in terms of the respective importance of humoral and cellular immunity to Brucella and of the choice of the best preparations for human or animal vaccination.


The fate of concanavalin A-stimulated lymphocytes in the spleens of recipient mice. The fate of mouse spleen cells, stimulated with Concanavalin (Con A) and labelled with [3H] thymidine in culture, has been followed after transfer into recipients, syngeneic to the cell donors. The labelled cells, localizing in the spleen, were found mainly in the white pulp in both germinal centre and periarteriolar sheath areas. The number of cells with labelled nuclei found in the spleens of recipients was much greater than could be accounted for simply on the basis of the radioactivity present. Using donor cells, whose DNA had been substituted with bromodeoxyuridine (BUdr) in sufficient amounts to increase its buoyant density, it was concluded that redistribution of label rather than cell division was responsible for this increase of labelled nuclei. In addition to these findings, the spleens of recipient mice showed evidence of a vigorous immunological response to the donor cells, very similar to that following injection of an antigen such as sheep red cells. These results show that caution must be exercised in interpreting the results of transfer of lymphocytes into recipients, even when a highly stable molecule such as DNA contains the radioactively-labelled material such as [3H] thymidine.


Production of C2 by human alveolar macrophages. Human and rat alveolar macrophages produce haemolytic C2 during in vitro culture. We conclude that C2 synthetic ability is maintained during in vivo maturation of human monocytes to macrophages and that production of complement components by mature tissue macrophages may be important for optimal generation of inflammatory responses.


Organophosphorus inhibition of lysosomal enzyme secretion from polymorphonuclear leucocytes. Evidence of a lack of a requirement for esterase activation. Previously, di-isopropylphosphorofloridate (DFP) was shown to inhibit the release of lysosomal enzymes induced by chemotactic factors. It was suggested that the inhibition was due to the phosphorylation of a cell bound serine esterase activated by the chemotactic factor. However, as shown here, di-isopropyl methyl phosphate, a nonphosphorylating analogue of DFP, inhibits just as well as DFP, the release of lysozyme and beta glucuronidase from rabbit polymorphonuclear leucocytes induced by chemotactic factor in the presence of cytochalasin B. Similarly, the poorly phosphorylating phenyl ethyl pentylphosphonate and phenyl ethyl phenylpropylphosphonate inhibit enzyme release, induced under the same conditions, as well as or better than the corresponding good phosphorylators, p-nitropheny ethyl pentylphosphonate and p-nitrophenyl ethyl phenylpropylphosphonate. Phenyl ethyl pentylphosphonate inhibits at least as well or probably better than p-nitrophenyl ethyl pentyl phosphonate, the chemotactic factor induced relase of lysozyme from polymorphonuclear leucocytes spread on Millipore filters in the absence of cytochalasin B. We conclude that, under the circumstances tested, there is no evidence that the release of lysosomal enzymes from rabbit peritoneal polymorphonuclear leucocytes induced by chemotactic factor involves the activation of an esterase.


Stimulation of human peripheral blood lymphocytes by Tamm-Horsfall urinary glycoprotein. Tamm-Horsfall urinary glycoprotein (THP), prepared by salt precipitation of pooled urine from normal individuals, stimulated purified human peripheral blood lymphocytes (PBL) to undergo blastoid transformation. the response was measured by tritiated thymidine uptake into DNA after 6 days in culture. Several batches of THP stimulated, in varying degrees, all samples of PBL tested and the response approached that seen with the mitogens phytohaemagglutinin (PHA), Concanavalin A (Con A) and pokeweed mitogen (PWM) after 4 days in culture. The response usually exceeded that seen after 6 days with tuberculin purified protein derivative (PPD) in Mantoux positive lymphocyte donors.


Visceral reflex responses following right intra-atrial injection of phenyldiguanide in rats. 1. Intra-atrial injection (right atrium) of pdg in nembutal anaesthetised rats produced bradycardia, hypotension and apnoea followed by hyperpnoea. In very lightly anaesthetised rats, injection of pdg close to the aortic valves produced similar responses and those responses disappeared on maintaining the animals in well-anaesthetised condition. 2. Administration of pdg either into the cerebral circulation or into cerebral ventricles did not produce bradycardia and apnoea. 3. The afferent pathway for these autonomic responses runs in vagus nerve, as shown by experiments before and after bilateral vagotomy. 4. The electrical activity of both expiratory and inspiratory muscles was inhibited during end-expiratory apnoea phase following injection of pdg into the right atrium. 5. Glycine, administered centrally or intravenously, exhibited blockade of pdg induced autonomic responses for more than forty minutes.


A correlative study of seminal biochemistry and testicular histology in infertile males. Two androgen-dependent constituents of the seminal plasma, fructose and acid phosphatase, have been estimated in 50 infertile males along with a testicular biopsy. Azoospermics, as a group, showed a very wide range of fructose (16-600 mg%) as compared to 210-397 mg% in healthy fertile males. Oligospermics tended to have low values with a mean of 218 +/- 75.1 mg%. Acid phosphatase in the controls was 1927 +/- 164.6 K.A. unit/ml and was generally higher in the infertile groups. The state of spermatogenesis, as revealed by testicular biopsy, bore no consistent relationship with the seminal fructose or acid phosphatase. It appears that there may be no inter-relationship between the activity of the germinal epithelium and the secretion of the accessory glands and, although both are androgen-dependent, they can be affected separately by a multitude of factors in human infertility.


Hypoglycemic responses to insulin in normothermic and hyperthermic young dogs. The present study was conducted in 10 healthy young dogs in which pattern of hypoglycemia to injected insulin (0.12 U/kg I.V.) was studied at normothermic (38.5 degrees C) and hyperthermic (42.5 degrees C) body temperatures. Average maximum fall in plasma glucose concentration from the control level was 44.3% and 53.8% in normothermic and hyperthermic dogs respectively. The hypoglycemic response to injected insulin was much greater and prolonged in hyperthermic dogs. The recovery of plasma glucose to preinjection level was also very sluggish and incomplete in these dogs. The above changes in hyperthermic animals may be due to enhanced secretion of insulin, as well as an increased sensitivity to injected insulin. The slow recovery of plasma glucose to preinjection level following insulin administration in hyperthermic dogs would indicate inefficient feedback mechanisms which normally operate to raise the plasma glucose during hypoglycemia.


Eliciting conditioned taste aversion by cobra venom neurotoxin in rats. An attempt is made to study conditioned taste aversion (CTA) using cobra venom antivenom or lithium chloride as the Unconditioned Stimulus (US). Twenty-four hour water deprived rats were habituated for two consecutive days to drinking tap water in the drinking box for 15 minutes daily. On 3rd day they were allowed to drink 0.1% sodium saccharin. Thirty minutes later, they were injected with cobra venom (45 micrograms), antivenom (0.022 microliter), antivenom followed by venom, lithium chloride (0.15 M, 4% body weight) or physiological saline. After two days of recovery the animals were water deprived for twenty four hours and water intake was measured on the 7th and 8th day. Retention test on the 9th day shows reduced saccharin consumption in the lithium chloride and venom groups. CTA was significantly reduced in the antivenom-venom group and absent in the antivenom and control group. It is concluded cobra venom can induce clear-cut CTA in rats.


Interactions between reserpine and anticonvulsants on convulsion parameters. Reserpine lowered the MET and this lowering of MET was antagonized by chloridaze-poxide but not by acetazoleamide and phenytoin. With increasing doses of reserpine the extension time in an MES test was increased and this was antagonized by all anticonvulsants tested namely acetazolamide, chlordiazepoxide, phenytoin and propranolol. High doses of reserpine abolished flexion component and this was restored by propranolol, phenytoin, atropine, chlordiazepoxide and acetazolamide.


Modification of hyperglycaemic effect of angiotensin by indomethacin. Effect of angiotensin II was studied on blood sugar level in dogs. Angiotensins given by intravenous route caused a marked rise in blood sugar level. Indomethacin and propranolol significantly influence the changes in blood sugar level induced by angiotensin. It is suggested that the hyperglycaemia induced by angiotensin appears to be mediated by facilitation of adrenaline and prostaglandin release.


Alteration in some hepatic dehydrogenases and certain lipid components in thiamin deficiency. An investigation was conducted to study the influence of thiamin deficiency on hepatic glucose-6-phosphate dehydrogenase, malic enzyme (NADP), lactate dehydrogenase and it's isoenzymes, total lipids, cholesterol and phospholipids in adult male albino rats. Typical thiamin deficiency symptoms developed in the 6th week. The specific activity of the said enzymes was significantly decreased in deficient rats as compared to pairfed controls. A significant drop in total lipid and phospholipid content was noted in deficient group while total cholesterol remained unchanged. Refeeding of control diet to deficient animals caused reversal of enzyme activities to normal.


Effect of oestrogen on the incidence of drumsticks in the rabbit neutrophils. Adult female rabbits were given daily intramuscular injections of 0.5 microgram of oestradiol diproprionate for four weeks. Weekly drum-stick counts were made from their blood smears and percent incidences of drum-sticks in the neutrophils was recorded. A highly significant increase in the drum-stick counts compared to the control animals was noted after one week's treatment with the oestrogen. Subsequent values after 2nd, 3rd and 4th week's treatment were not significantly different from values obtained from the corresponding untreated animals. It was concluded that oestrogen produces only an initial increase in the drumstick count and subsequent continued treatment neither increases nor decreases the drum-stick counts significantly.


Small intestinal and hepatic amylase activity of different vertebrates and invertebrates. Studies have been done on amylase activity of the small intestine and liver of toad, calotes, pigeon rat, guinea pig and pilaglobosa. It has been found that amylase activity was maximum in pigeon, rat, guinea pig and then in calotes and pilaglobosa and least activity was found in toad, and seem to be related to the phylogeny and the dietary habbit.


Modelling the cell-mediated immunity in homograft refection. Lymphocytes which become sensitised at the periphery travel to the regional lymph nodes where they initiate an immunological response by increasing the production of immuno-competent lymphocytes. These lymphocytes migrate into the tissues via the blood stream and bring about the destruction of target cells. These notions, in the present analysis, are translated into a simple mathematical model. The model specifically considers the lymphocyte memory and increased secondary response.


[Minicomputer system to automate the input of stimuli and the collection of related response parameters]. This paper describes a system based on a minicomputer that enables one to automate the input of stimuli and to collect a certain number of parameters directly obtained from the analog signals representing the responses of the tested subject.


Discussion on basic equations for a flow in human air passages and their representation. Basic equations of time-dependent flow are discussed in the case of rigid or elastic branches and according to the airway representation pattern, both continuous and discontinuous. Two relevant fundamental continuous functions are defined: the 'order of generation' G(x) and the cumulative bronchial diameter D(x). A numerical solution is outlined in the former case, then in the latter case, and the system of equations which completely describes the flow is solved.


On-line electro-oculography.

On-line electro-oculography. The design and use of an on-line PDP 11/40-based system for quantitative study of ocular kinetics are described. The system can be used in neurophysiological or ophthalmological applications. Two different techniques are presented. In one, horizontal, vertical or oblique eye motion can be studied, in the other horizontal eye motion only. Several parameters of eye motion can be measured including saccadic velocity, eye movement latency and accuracy of refixation. For ophthalmological EOG applications the system allows measurement of the absolute voltage excursion corresponding to a horizontal eye movement of a specific amplitude. The system consists of five software programs and supporting signal processing equipment. The software package runs under the RSX11M executive.


Certain observations in electrocardiogram and enzyme variation in dogs, following scorpion venom injection. The effect of scorpion venom of Buthus Tamulus species on blood pressure, ECG, enzyme and electrolytes were studied in dogs. Venom was given in doses of 2 and 4 mg/kg body weight. Hypotension and tachycardia were observed with low dose and bradycardia was significant with high dose. ST segment depression, T wave changes, shortening of PR interval were the important ECG changes apart from ventricular extrasystoles. With high dose, QRS amplitude was reduced and duration prolonged. QTC interval was also significantly prolonged. Significant increase in SGOT, SGPT and LDH levels were observed but no change in serum electolytes was seen.


The impact of work/study programs on employment of the mentally retarded: some findings from two sources. There were two purposes of this study. The primary goal was to examine the employment success of both graduates and early terminators from high school work/study programs for educable retarded young adults (16--21 years old). A second goal was to study the employment levels of these same mentally retarded persons. Data sources included the vocational placement results of students who terminated from work/study programs in 14 Oregon school districts, along with analogous information about work/study terminators from 43 Federally funded work/study projects conducted in the United States between 1955 and 1972. Both the Oregon and the Federal program participants demonstrated that mentally retarded persons who finished their work/study programs had substantially higher employment levels than did similar retarded persons not completing or only partially served by their programs. Also, work/study program completors had comparable employment levels with same age non-white adults in the general population.


Highlights on the etiology of keloid.

Highlights on the etiology of keloid. The keloid phenomenon is old and perplexing. Many hypotheses were advanced to account for keloid growth but none of them provided a satisfactory explanation for the clinical manifestations of the disease. To solve the mystery of keloid detailed clinical studies coupled with laboratory tests were undertaken on keloid and non-keloid individuals; these highlighted the determinants of the disease and paved the way to the formulation of the Sebum Auto-immune Theory. The latter provided valid explanations for the clinical manifestations of the disease and indicated a rationale for new trends of management.


Globin-chain synthesis in Hb H disease: the activity of red cell precursors and their mRNA. Globin-chain synthesis was determined in bone marrow and blood of four patients with Hb H disease and in a cell-free system supplemented with poly(A)-rich RNA from the patients. The relative synthesis of alpha-globin ranged between 0.36 and 0.49 in erythroid precursors and between 0.09 and 0.28 in reticulocytes. The relative quantity of biologically active alpha-globin mRNA in poly(A)-rich RNA from bone marrow and blood of these patients ranged between 0.09 and 0.21. The findings suggest the operation, within alpha-thalassemic bone marrow cells, of a translational control mechanism and/or the instability of alpha-globin mRNA.


Pneumatosis cystoides intestinalis and jejunoileal bypass. The authors present a case of pneumatosis cystoides intestinalis, observed by chance in a patient previously subjected to end-to-end jejunoileal bypass for severe obesity. Using their observation and the cases reported in the literature as a starting point, the authors discuss the etiopathogenetic and clinical aspects of the disease, and briefly indicate what is, at present considered the correct therapeutic approach.


Iron chelation in thalassemia: mechanism of desferrioxamine action. The mechanism of iron chelation was studied in 16 patients with homozygous beta-thalassemia. Following the i.v. infusion of desferrioxamine, chelated iron accumulated in the plasma and its maximal level at 2 h was closely correlated with the 24-h excretion of iron in the urine. The high specific activity of chelated urinary iron indicated that the chelatable pool was much smaller than the total storage iron pool and was probably derived from nonviable red blood cells in the reticuloendothelial system. This postulate was confirmed by the direct measurement of specific activities in the spleen and liver, revealing identical values of chelated urinary iron and of iron in reticuloendothelial tissues. These findings support the concept of an easily chelatable iron pool that is derived from the catabolism of hemoglobin.


Ultrasonography: its continuing value in diagnostic ophthalmology. This case history re-emphasizes the absolute necessity for all cases of leukokoria or opaque media, where a view of the fundus is impossible, to have preliminary "A" or "B" scan ultrasonography. In 1960 perhaps only two or three institutions had the high resolution "B" scan equipment at their disposal. Today at least 75 units are in use throughout the U.S., including a larger number of the calibrated "A" scans. In fact, ultrasound is a valuable adjunct before any cataract surgery, vitrectomies, I.O. lens implantations, or retinal detachment surgery. Ultrasound is perhaps the only non-invasive technique available today in the ophthalmological armentarium for soft tissue differentiation using acoustic wave fronts. This case amply demonstrates the legal and technical problems had the surgeon planned to perform "cataract" surgery, and possibly a corneal transplant. The anguish avoided by both the surgeon and patient is obvious.


Absence of functional beta-globin messenger RNA in Kurdish Jews with beta0-thalassemia. Human globin messenger RNA was isolated from reticulocytes of four Jewish patients of Kurdish origin with homozygous beta0-thalassemia. On translation in the wheat-germ cell-free system, messenger RNA from these patients directed extensive synthesis of alpha- and gamma-globin chains, but synthesis of beta-globin chains was not detectable. In contrast, nonthalassemic human globin messenger RNA directed the synthesis of essentially equimolar amounts of alpha- and beta-globin. The patterns of globin synthesized by beta0-thalassemic messenger RNA in the cell-free system were virtually identical to the patterns of globin synthesized in peripheral blood cells of these patients. beta0-thalassemic messenger RNA similarly failed to direct any detectable beta-globin synthesis in a micrococcal nuclease-treated rabbit reticulocyte lysate, even in the presence of an excess of purified eukaryotic initiation factor 2. These results strongly suggest that functional messenger RNA for beta-globin chains is absent in Kurdish Jews with homozygous beta0-thalassemia.


Serum ferritin in beta-thalassemia trait. The diagnostic value of serum ferritin measurements in discriminating iron-deficiency anemia from thalassemia trait has been studied. In contrast to serum iron, percent transferrin saturation and total iron-binding capacity, where a high degree of overlap existed between the two groups, a clear-cut difference in serum ferritin levels was found between iron deficiency and thalassemia trait. The best separation of iron deficiency, thalassemia and normal controls was given by the combination of mean corpuscular volume and serum ferritin. Although definitive diagnosis of beta-thalassemia trait requires the demonstration of abnormal Hb A2 levels or beta-chain synthesis, serum ferritin is a useful screening test for the initial diagnosis of thalassemia trait. Because of the very small amounts of serum required for the measurement of ferritin, it is particularly suitable for surveying populations with a high prevalence of hypochromic-microcytic anemias.


Hemorrhagic tendency in beta-thalassemia major. A mild hemorrhagic tendency was observed in a group of beta-thalassemia major patients. This included easy bruising and frequent epistaxis. A consistent platelet anomaly manifested by diminished platelet aggregation to ADP, collagen, ristocetin and epinephrine was found in these patients, and could be responsible in part for the hemorrhagic phenomena.


An unusual type of congenital dyserythropoietic anemia with thalassemia features. A 25-year-old male patient of Kurdish Jewish origin presented with mild anemia and splenomegaly. The acidified serum test was strongly positive with three of four normal sera and the anti-i agglutination of the red cells was negative. Hemoglobin electrophoresis showed an increase of Hb A2 (3.4%). Blood smears showed changes compatible with thalassemia. On bone marrow examination, approximately 3% of the normoblasts showed changes typical of dyserythropoiesis, including binucleated orthochromatic normoblasts and large trinucleated and quadrinucleated megaloblasts. Ultrastructural studies of the bone marrow cells revealed characteristic features of congenital dyserythropoietic anemia, including irregular cytoplasmic pseudopodia, perinuclear cisternae, intrusion of cytoplasmic material into the nucleus and incomplete cytoplasmic cisternae.


Aberrant congenital dyserythropoietic anemia with negative acidified serum tests and features of thalassemia in a Kurdish family. Three siblings of a Kurdish Jewish family with clinical and hematologic findings compatible with congenital dyserythropoietic anemia (CDA) are described. All patients presented with mild anemia, marked hyperbilirubinemia and splenomegaly. The bone marrow morphology and ultrastructure of the normoblasts was typical of CDA type II and there was strong agglutination of the patients' red blood cells by anti-i serum. These patients displayed two features that were not characteristic of CDA type II, namely, the acidified serum lysis test was negative on more than 10 occasions, and high levels of Hb A2 were observed in two siblings. In one of the siblings, abnormal globin-chain synthesis was found and alpha-chain production exceeded beta-chain production, as in beta-thalassemia minor. In the light of the above findings, our patients are perhaps best classified as having aberrant CDA with features of thalassemia.


Kinetics of erythroblast proliferation in states of hypoferremia. By application of the method of quantitative 14C-autoradiography, the kinetics of erythroblast proliferation were studied in seven patients with iron-deficiency anemia (IDA), in five cases of anemia associated with infection or malignancy (ACD), and in two patients with bleeding anemia (BLA). The turnover rate of erythroblasts was significantly reduced in IDA and ACD, and was normal in BLA. Proliferation and maturation of erythroblasts in IDA and ACD were increasingly slowed down with advancing development into mature cells. Neither changes in the number of cell divisions nor ineffective erythropoiesis were observed within the proliferative compartments. The kinetic impairments found in IDA and ACD could readily be counterbalanced by a twofold increase in the rate of stem cell differentiation. Within recognizable erythropoiesis, no compensatory effort was detectable, not even in proerythroblasts. Insufficient compensation at the stem cell level is therefore regarded as the prime lesion in IDA and ACD.


Cell separation, cell differential and granulocyte colony frequency in polycythemia vera. In seven patients with polycythemia vera, the agar colony growth of bone marrow total nucleated cell suspensions and of the cell fractions obtained with an albumin discontinuous density gradient were studied. In one patient, the density distribution of colony-forming units in culture (CFUc) before and after alkylating treatment was evaluated and cell differentials on smears obtained from each density fraction were determined. A high percentage of low density CFUc compared with the total CFUc population and with that in the normal control subjects in the same density fractions was observed.


Hyperlipemia and myocardial infarction in polycythemia vera. Hyperlipemia was found in 46 of 118 polycythemia vera patients and in 20 of a control group of 115 healthy subjects. Myocardial infarction in the polycythemia vera group occurred in 14 of the 46 hyperlipemic and in 17 of the remaining 72 nonhyperlipemic patients. Repeated phlebotomies may induce hyperlipemia; therefore, this form of treatment may be potentially dangerous in polycythemia vera patients who are already hyperlipemic.


Human red blood cell membrane adenylate cyclase in sickle-cell disease. The basal and the NaF-stimulated activities of human red blood cell membrane adenylate cyclase were found to be 5.3 +/- 0.8 (SE) and 219 +/- 76 (SE) pmol . mg-1 . min-1, respectively. Both activities were increased in nine patients with homozygous sickle-cell disease. There was no apparent correlation between this increase and the increase in the reticulocyte count.


Heme synthesis in anemia of the uremic state. Anemia is a constant complication of uremia. As it has been suggested that uremic toxins (middle molecules) play an important role in the mechanism of anemia, we studied the activities of three heme-synthesizing enzymes: delta-aminolevulinic acid dehydratase, porphobilinogen deaminase and ferrochelatase. In 26 patients on regular dialysis therapy, all three enzymes had significantly lower values than in normal control subjects. From our results, it can be assumed that the decreased heme biosynthesis in chronic uremic patients might be caused by a lack of erythropoietin or by uremic toxins inhibiting erythropoietin and/or heme-synthesizing enzymes.


Combined glucose phosphate isomerase and glucose-6-phosphate dehydrogenase deficiency of erythrocytes. A patient with combined deficiency of erythrocyte glucose phosphate isomerase (GPI) and glucose-6-phosphate dehydrogenase (G6PD) is presented. The propositus has persistent unconjugated hyperbilirubinemia. One of his two brothers exhibits the same rare enzymatic defect, but without any clinical symptoms. The electrophoretic pattern of GPI showed GPI type 1. There seems to be a correlation between the unconjugated hyperbilirubinemia and the combined enzymopathy in our patient.


Hepatic sinusoidal cells in iron overload. Ultrastructural observations. The ultrastructure of sinusoidal cells was studied in 18 liver biopsies from patients with homozygous beta-thalassemia. No conspicuous iron was seen in sinusoidal cells from biopsies obtained before transfusion therapy was initiated, although electron-dense iron was present in some parenchymal cells. Biopsies following the high transfusion regime showed progressive increase in the size and number of iron-containing lysosomes in both parenchymal and sinusoidal cells. This study confirms the view that transfusional iron is largely segregated in reticuloendothelial cells. Examination of stained and unstained sections showed the Kupffer cells and endothelial cells had different types of iron-containing lysosome that were also dissimilar from most iron-containing lysosomes seen in hepatocytes. The described cell-specific morphological features of the lysosomes facilitate the identification of various cells during iron overload. The importance of phagocytic sinusoidal cells during chronic iron overload is stressed.


Beta-chain variants in Jamaican newborns. In an electrophoretic study of 15,661 Jamaican cord bloods, 8 rare beta-chain variants were found in 18 subjects in addition to the common beta-chain variants, Hb S and Hb C. The heterozygote frequencies for Hb S and Hb C were 10.1% and 3.7% respectively. The most frequent of the rare beta-chain variants were Hb Korle Bu (beta 73 Asp leads to Asn) (7 cases) and Hb O su-Christiansborg (beta 52 Asp leads to Asn) (3 cases). One new beta-chain variant, Hb Caribbean (beta 91 Leu leads to Arg) was found.


Delta beta-thalassemia in a Mexican family: clinical differences among homozygotes. Three delta beta-thalassemia homozygotes were found in a Mexican family. Both parents and two sibling had heterozygous delta beta-thalassemia with about 10% Hb F, mild microcytosis and mild hypochromia, while three siblings were normal. Hb F, which was the only Hb component in the homozygotes, had equal quantities of Ggamma and Agamma chains as in BgammaAgamma-delta beta-thalassemia. The homozygotes had comparable erythrocytic indices which were about the same as those of the heterozygotes. However, two were clinically and hematologically healthy but the third had a severe chronic hemolytic anemia and a more severe in vitro chain synthesis imbalance than her homozygous sisters. Comparison of these cases with other GgammaAgamma-delta beta-thalassemia homozygotes and with GgammaAgamma-HPFH homozygotes indicates the possibility that the proliferation of F-cell precursors may be defective in delta beta-thalassemia.


Hemoglobins Aida (alpha 64 Asp leads to Asn) and D-Los Angeles (beta 121 Glu leads to Gln) in an Asian-Indian family. Hemoglobins D-Los Angeles (beta 121 Gln) and Aida (alpha 64 Asn) were encountered in an Asian Indian, unassociated with any clinical manifestations. These hemoglobins had normal oxygen affinities and were stable to heat and isopropanol. The ratio of alpha chain synthesis to beta chain synthesis was close to unity. The identical change in isoelectric points of the two variants produced an interesting electrophoretic pattern.


Hemoglobin Hofu or alpha 2 beta 2 [126 (H4) Va1 leads to Glu] found in combination with hemoglobin S. Hb Hofu, alpha 2 beta 2 [126 (H4) Va1 leads to Glu], was found in 10 members of 2 apparently unrelated Valmiki families in central India. None showed evidence of hemolysis and hemoglobin levels were normal in most. In two individuals, Hb Hofu occurred in combination with Hg S, but neither had clinical manifestations of sickle cell disease. In samples containing Hb Hofu, the isopropanol precipitation test was positive. Quantitation of the hemoglobin fractions by DEAE-cellulose chromatography showed that Hb Hofu constituted a mean of 23--25% of the total whether in combination with Hb A or Hb S.


Evaluation of triiodothyronine (T3) kinetics in normal subjects, in hypothyroid, and hyperthyroid patients using specific antiserum for the determination of labeled T3 in plasma. Triiodothyronine (T3) kinetics was evaluated using [125I]T3 and the single injection technique; 5 hypothyroid, 6 hyperthyroid patients, and 10 euthyroid control subjects were studied. Plasma-labeled T3 concentration was measured by means of a new method based on extraction of the hormone on Sephadex G-25 columns followed by elution with the specific antiserum. This technique allows a far better separation of the hormonal radioactivity from the labeled iodide produced from T3 catabolism in comparison with the TCA-precipitation-butanol extraction method. The analysis of the experimental data has been performed using non-compartmental treatment (integral approach); results of mono-compartmental analysis of the same data are also reported for comparison. Average metabolic clearance was 15.3 +/- 0.6 (mean + SEM) liters/day/m2 body surface in normal subjects; it was significantly decreased in hypothyroid patients (11.4 +/- 1.1) and significantly increased (33.4 +/- 4.0) in hyperthyroidism. The total plasma equivalent distribution volume was found significantly enlarged in hyperthyroid patients (22.6 +/- 0.9 liters/m2) in respect to that measured in the control group (15.6 +/- 0.4), whereas it was not different from normal value in hypothyroid patients (17 +/- 1.7). Using plasma concentration of native T3, absolute turnover rate and extrathyroidal pool were also estimated; their values were 6.5, 23.7, and 131.7 micrograms/day/m2 and 10.1, 24.2, and 90.6 micrograms/m2, respectively, in hypothyroid, normal, and hyperthyroid groups.


Effects of altered free fatty acid mobilization on the metabolic response to exercise. This study was designed to evaluate the metabolic response to limitation of fat mobilization during severe exercise in man. To this end, we assessed the relationship between fat mobilization, lipid-ketone physiology, and exercise-induced elevations in the counter-regulatory hormones. Ten well trained athletes ran a 10-mile premeasured course in as short a time as possible during both a placebo and an experimental study. In the experimental study, fat mobilization was inhibited by the oral administration of 2 g of nicotinic acid. Blood samples for multiple substrate and hormonal assay were obtained 2 h before exercise, immediately before exercise, and immediately after exercise. In the experimental study, nicotinic acid effectively blocked the expected rise in plasma free fatty acid concentration observed in the placebo study. Although blunted, the exercise-induced rise in plasma ketone concentration persisted in spite of the reduced free fatty acid levels. The significance of the concommitant exagerated rise in glucagon and GH in stimulating ketogenesis is discussed. The inhibition of fat mobilization did not reduce the mean time required to run 10 miles. Since muscle uptake of free fatty acid is directly proportional to the plasma concentration of this substrate, our study suggests that the inability to mobilize fat does not prevent severe exercise for 70 min.


Assay of unbound cortisol in plasma.

Assay of unbound cortisol in plasma. A method for measuring the unbound fraction of plasma cortisol which is suitable for clinical use is described. It is shown that unless some precise experimental conditions are fulfilled, important errors may result when determining the unbound fraction of the hormone. The assay is practical (2 ml of plasma are necessary) and reproducible (coefficient of variation: 2.7% within the same assay and 3.1% in different assays). Unbound cortisol measured at 0800 h in 86 healthy individuals was 9.7 +/- 2.6% (SD) of total cortisol and 15.0 +/- 8.5 ng/ml of plasma (temperature: 37 C). No significant difference was found between men and women or according to age. In most cases, variations of unbound plasma cortisol were more important than the variations of total plasma cortisol. This explains why unbound cortisol was a better discriminator in some pathological conditions. In Cushing's syndrome unbound cortisol was found to be increased on the average 2.9 fold whereas total cortisol was only increased by 53%. Unbound cortisol was especially high (24.7 +/- 3.8% of total cortisol and 78 +/- 18.5 ng/ml of plasma) in Cushing's syndrome due to adrenal carcinoma. In adrenal insufficiency, unbound cortisol averaged 6% of total cortisol and 1.4 ng/ml of plasma.