[Treatment of tonsillitis with dequalinium chloride]. 44 children with acute tonsillitis were treated without the usual penicillin therapy. 22 children received lozenges containing Dequalinium chloride, 22 children received void lozenges under conditions of a double blind study. The results show that the treatment with Dequalinium chloride did not influence conditions caused by haemolytic streptococci -- verified by bacteriological examinations of pharyngeal smears -- inspite of its efficiency in vitro. Also general symptoms like fever, leukocytosis and rapid erythrocyte sedimentation rate were not influenced by Pequalinium chloride. Local symptoms like sore throat, tonsillar redness and exsudation were influenced beneficially. It can therefore be assumed that in cases of acute tonsillitis penicillin therapy is not necessary except in cases of streptococci infections. These should be excluded by pharyngeal smear. The medium of Liebermeister and Braveny is a very simple indicator to differentiate between tonsillitis caused by streptococci and tonsillitis of other origin.


[Principles in the therapy of osteoporosis. 2. Therapy]. "Osteoporosis" is no disease by itself, but solely an anatomically equal result of various etiologic and pathogenetic influences on the bone structure or parts of same. A therapeutic effect and prognosis are dependent on these conditions to a considerable extent. Practically, it is therefore of paramount importance to distinguish between various clinical pictures of osteoporosis as well as to separate them from hypostotic changes of the skeleton. No more than a single type of "osteoporosis" exists, a uniform treatment can be applied. Cause and extent of the change, age and sex of the afflicted, individual complaints and complications determine the therapeutic procedure in every case. Jointly, all efforts tend to stop the decrease of the bone tissue inherent in the porosity, and to achieve, whenever possible, a compensatory increase of the bone structure still remaining by stimulation of the osteopoiesis.


[Current treatment of depressions using psychopharmacologic agents]. After an introduction some reflections are discussed which enable the general practitioner to decide the question whether to treat the patient inside or outside the hospital. In this respect some factors are of influence: severity of illness, suicidal tendencies, sleep distrubances, possibility of collaboration with the family and others. Then criteria for the selection of suitable antidepressant are discussed. Most suitable are sedative antidepressants. The beginning, the dosage and the duration of therapy are described. Today great importance has the prophylaxis of monopolar and bipolar depressions, especially the prophylaxis with lithium salts. Side effects are discussed with special references to a newer substance with few side effects as well as questions of the cardiotoxicity and of impairment of driving ability.


[Prevention of idiopathic respiratory distress syndrome. Influence of betamethasone on the frequency of respiratory distress syndrome in a premature infant collective at the Bonn University Gynecologic Clinic]. Out of a group of 189 pregnant women, who were in the 28th to 37th week of gestation, 57 women received i.m. injections of betamethasone. 132 premature infants whose mothers were not treated served as controls. Betamethasone caused a significant decrease in established respiratory distress syndrome (RDS). In the betamethasone group there was an incidence of 7% of respiratory distress syndrome as compared to 23,5% in the control group. Neonatal mortality was 1,8% in the treated group versus 10,6% in the control group. The occurrence of suspected respiratory distress syndrome also was significantly lowered after betamethasone. In the control group premature rupture of membranes or administration of tocolytic drugs did not have any effect on the frequency of respiratory distress syndrome. However, the premature babies who were delivered by caesarian section had a significantly higher incidence of respiratory distress syndrome than those who were delivered vaginally. After betamethasone treatment the occurrence of respiratory distress syndrome after caesarian section was as low as in the group with vaginal delivery. The present study of a larger group of premature babies has confirmed previous positive results of betamethasone treatment.


[Prevention and therapy of the respiratory distress syndrome in premature infants using lecithin. Distribution of 14C--labeled lecithin after intravenous and intraamnial administration in pregnant miniature pigs?]. The aim of our researches was to point out a new therapeutical possibility to prevent a respiratory distress syndrome of prematures by application of 14C-lecithine. The experiments were carried out at Göttinger mini-pigs. Examining the placental passage it could be determined that an intravenous application was not efficient, while after intraamnial application of lecithine a rapid resorption in the fetal organism was proved. Of special interest was a high accumulation of lecithine in the fetal lung-tissue. These results indicate a possible therapeutical way to prevent a respiratory distress syndrome by lecithine substitution.


[Diagnosis of cancer and early detection. Clinical methods]. The etiology of cancer--as one of the most important causes of death--remains unknown. Therapy seems promising only in its early stages and if the exact diagnosis of carcinoma is possible. Diagnostic procedures today have gained a high standard demonstrated on malignancies of the gastrointestinal tract and the lung. The whole spectrum of methods can be employed only after having selected the patients according to "high risk" groups and methods of early cancer detection respectively. Effective and pragmatic progress has been made but is not fully utilized yet. Future trends in the diagnostic development are discussed.


[Sulpiride in the prevention of migraine. A mechanism of hormonal interaction?]. In women migraine attacks are often related to hormonal changes and it has been demonstrated that migraine attacks correlate with falling plasma estrogen levels. Sulpiride, a benzamide derivative with neuroleptic and thymoleptic properties, is known to act at the hypothalamic level and in particular, to inhibit releasing factors responsible for follicle-stimulating hormone and prolactin secretion. In this way, sulpiride keeps estrogen levels low and prevents major fluctuations. 34 women and 6 men with classical, recurrent attacks of migraine were treated with sulpiride 300 mg/day, for several month and up to a two-year period. Of these, 55 percent became completely free of migraine, 20 percent improved, and the remaining 25 percent did not benefit. When sulpiride was withdrawn, migraine frequently recurred. Side effects were related to the above-mentioned hormonal changes: amenorrhea or delayed menstruation in 60 percent, breast tension in 40 percent and transient galactorrhea in 14 percent. Some weight gain was reported from allmost all patients.


[Basic peptides in bee venom, III. Synthesis of peptide fragments from the sequence of the mast-cell-degranulating peptide (author's transl)]. The synthesis by conventional methods of the following three peptides is described: MCD(8-11) Boc-His(Trt)-Val-Ile-Lys(Z) (III) MCD(5-7) Boc-Cys(SiPr)-Lys(Z)-Arg(Tos) (IV) and MCD(1-4) Boc-Ile-Lys(Z)-Cys(Trt)-Asn(Mbh) (V). These peptides are fragments of the mast cell degranulating peptide from bee venom. The purity of the fragments synthesized was examined by thin-layer chromatography, amino acid and elementary analysis. Including the fragments Boc-Lys(Z)-Ile-Cys(SiPr)-Gly-Lys(Z) (I) and Boc-Pro-His(Trt)-Ile-Cys(Trt)-Arg(Tos) (II), which were described earlier, the synthesis of the mast-cell-degranulating peptide on a polyethylene-asparagine support appears possible.


[On cobyrinic acid biosynthesis. Novel methylated hydroporphyrins and their role in cobyrinis acid formation (author's transl)]. Clostridium tetanomorphum and Propionibacterium shermanii were examined for intermediates in the synthetic pathway uroporphyrinogen III leads to cobyrinic acid. The isolation of two novel methylated hydroporphyrins, whose methyl groups are derived from S-adenosyl-L-methionine, is described. Spectroscopic (field desorption-mass, visible absorption) und electrophoretic studies as well as incorporation of labelled substrates indicate that they are analogues of a dihyrouroporphyrin and a tetrahydrouroporphyrin with adjacent reduced rings. Field desorption spectra of the [C2H3]- and [CH3]-tetrahydrouroporphyrin analogues show that the compound contains two methyl groups; it is concluded that the chlorine-like compound has one methyl group. Dehydrogenation experiments indicate that the methyl groups are located at one beta-carbon of the reduced rings. Incorporation experiments suggest that the tetrahydrouroporphyrin-like compound is an intermediate in cobyrinic acid biosynthesis. Studies on the utilization of a heptacarboxyporphyrinogen from C. tetanomorphum for cobyrinic acid formation are also described.


Isolation and separation of inositol 1-phosphate, cyclic inositol 1,2-phosphate, and glycerylphosphoinositol from tissue culture cells labeled with [3H]inositol. Water-soluble phosphorylated inositol derivatives have been separated from each other and from inositol by ion exchange and by thin-layer chromatography. The method, in combination with radioactive labeling, is sensitive enough to be applied to single tissue culture dishes corresponding to 10(6) - 10(7) cells. With this technique glycerylphosphoinositol, inositol 1-phosphate, cyclic inositol 1,2-phosphate, and at least three other inositol labeled compounds can be detected in human, monkey, hamster, mouse, and Japanese quail fibroblasts. During a 24-h incubation with [3H]inositol the extent of labeling of these compounds differed according to the cell type.


Inhibition studies on Vibrio cholerae neuraminidase. A series of viral neuraminidase inhibitors showing no structural analogy to neuraminic acids have been tested to find whether they are effective inhibitors of V. cholerae neuraminidase, too. Here we report the results obtained with the N-phenyloxamic acid derivatives 2 to 6 (R-NH-CO-COOR'; R = -C6H5NO2, -C6H5OH, -C6H5NH2; R' = -H, -C2H5; see Table 1) and with simple aromatic compounds structurally related to R, i.e. 4-nitroaniline (7), N-acetyl-4-nitroaniline (8), 4-nitrophenol (9), 2,4-dinitrophenol (10), and 4-aminophenol (11) (see Table 2). The inhibitory effects of 2 to 11 were studied according to the method of Dixon[19] in 0.1m sodium acetate buffer, pH 5.5, 2mM CaCl2, at 37 degrees C using the benzyl-alpha-ketoside of N-acetyl-D-neuraminic acid (1) as a substrate. The compounds 2 to 11 are shown to be competitive inhibitors of the enzymatic hydrolysis of the alpha-ketoside 1. The competitive inhibition kinetics are supported by the method of Lineweaver and Burk[20]. The inhibition constants (Ki) are found to be in the range of 0.03 to 5.7 mM. The simple aromatic compounds 7 to 11 show higher inhibitory activities than the phenyloxamic acid derivatives 2 to 6. In addition, significant differences in the Ki values were observed within the two series of inhibitors, whereby those containing a nitro group were most effective.


Miliary aneurysms and "fibrinoid" degeneration of cerebral blood vessels. Three cases of intracerebral hemorrhage are described in which there was fibrinoid degeneration of cerebral arteries and arterioles or miliary aneurysms or both. Fibrous balls are shown to be sclerosed true aneurysms. These changes occurred in the absence of malignant hypertension and perhaps in the absence of any hypertension. A further point of  interest was the finding of fibrinoid at the site of apparent aneurysm formation in a small artery on the cerebral surface, a location at which miliary aneurysms are not generally thought to form. The presence of intracerebral hemorrhage in all three cases, and the ready demonstration of similar changes in other cases of intracerebral hemorrhage, suggest but do not prove that the fibrinoid degeneration or aneurysm leads to vessel rupture and to hemorrhage itself. Also unsettled is the question of whether miliary aneurysms form only at sites already displaying fibrinoid change. Our data suggest that pre-existing fibrinoid may not be a prerequisite for miliary aneurysm formation.


Congenital cystic adenomatoid malformation of the lung. Classification and morphologic spectrum. Thirty-eight cases of congenital cystic adenomatoid malformation of the lung are described, and a classification based on clinical, gross, and microscopic criteria is proposed. The type I lesion is composed of single or multiple large cysts (more than 2 cm. in diameter), frequently producing mediastinal herniation. The cysts are lined by ciliated psuedostratified columnar epithelium. The walls of the cysts contain prominent smooth muscle and elastic tissue. Mucus producing cells are present in approximatley one-third of the cases, and cartilage in the wall is rarely seen. Relatively normal alveoli may be seen between the cysts. The prognosis is good. Radiographic analysis of the type I lesion can preoperatively suggest the diagnosis, especially with the typical multicystic pattern. The gross appearance of the lesion corresponds closely to the radiographic image and adds another dimension to the pathologist's evaluation of the disease. The type II lesion is composed of multiple small cysts (less than 1 cm. in diameter) lined by ciliated cuboidal to columnar epithelium. Structures resembling respiratory bronchioles and distended alveoli are present between the epithelium lined cysts. Mucous cells and cartilage are not present. Striated muscle fibers may be seen rarely. The type II lesion is associated with a high frequency of other congenital anomalies, and the prognosis is poor. The type III lesion is a large, bulky noncystic lesion producing mediastinal shift. Bronchiole-like structures are lined by ciliated cuboidal epithelium and separated by masses of alveolus-sized structures lined by nonciliated cuboidal epithelium. The prognosis is poor.


IgA nephropathy.

IgA nephropathy. This presentation attempts to define the criteria for diagnosis of the suggested clinicopathologic entity of IgA nephropathy. Of 250 patients in whom renal biopsies with immunofluorescence, light and electron microscopic, and clinical data were available, 12 patients (4.8 per cent) showed predominance of IgA with localization mainly in the mesangium, a variable degree of mesangial cell proliferation, and increased mesangial matrix on light microscopy. Electron densities were restricted to the mesangium and paramesangial areas. IgA was accompanied by C3 only in two patients, by IgG and C3 in five, and by IgG, IgM, and C3 in five. Properdin was found in 11 of these 12 cases. There was a marked male predominance. All showed gross or microscopic hematuria and variable proteinuria. Ten had had normal renal function tests at the time of presentation, and there was no significant worsening of renal function in the 11 patients followed for six to 84 months after biopsy. No morphologic change was detected in two repeat biopsies six and seven years after the initial biopsies. These 12 patients appear to form a distinct clinicopathologic entity. They can only be separated from  other glomerular disorders with IgA when the morphologic and clinical findings are considered in combination with the finding of diffuse IgA predominance on renal biopsy.


Adenocarcinoma of the rete testis: a review of the literature and presentation of a case with associated  asbestosis. Although scattered reports of adenocarcinoma of the rete testis have previously appeared and criteria for the diagnosis of this tumor have been defined, previous cases have not been described in sufficient detail to provide an organized account of the nature and behavior of this neoplasm. The present report describes a case followed to autopsy and provides conclusive evidence that it is of rete testis origin. Previously reported cases of rete testis carcinoma are reviewed and the salient features summarized, showing that the tumor has a definite clinical and histologic pattern and that the prognosis appears poor. The present case occurred in a patient with severe pulmonary asbestosis. This association is unique, and its significance remains speculative.


Osteoid: an ultrastructural study.

Osteoid: an ultrastructural study. Iliac crest bone biopsy specimens from 34 patients were examined with the electron microscope. Although the biopsy examinations were undertaken because of suspected metabolic or hematopoietic disease, neither clinically nor by light microscope was any evidence of disease identified. The layer of bone matrix between the osteoblast and the mineralized bone, usually referred to as "osteoid," is found not to be a homogeneous mass but to show a constant sequence of maturation and organization of collagen fibrils and mucopolysaccharides. This pattern was found to be modified in a situation of rapid bone formation such as normal fetal bone or in disease states such as Paget's disease of bone. These observations are of paramount importance in the evaluation of metabolic diseases of bone and in the identification of bone formation by mesenchymal neoplasms.


Fatal anhydrous ammonia inhalation.

Fatal anhydrous ammonia inhalation. The morphologic and morphometric pulmonary alterations in a patient with anhydrous ammonia inhalation dying two months after exposure are described. Major pathologic findings included cylindrical bronchiectasis of the lower lobes, fibrous obliteration of small airways, and terminal nocardial pneumonia. Normal density of small airways was found, but the average diameter (0.50 mm.) was significantly less than that of controls (0.66 +/- 0.02). Fibrous obliteration of small airways may be characteristic of a late stage of bronchiolitis obliterans and is probably responsible for the chronic obstructive lung disease in the survivors of an episode of ammonia inhalation.


Glomerulopathy and arteriolopathy in congenital nephrotic syndrome: light, electron, and fluorescence microscopy studies. This report describes the light, electron, and fluorescence microscopy studies of the kidney from a one month old, prematurely born infant with the nephrotic syndrome. Light microscopy revealed enlargement of Bowman's space, an excessive number of glomerular epithelial cell nuclei, and cystic dilatation of cortical tubules. By electron microscopy two disparate types of glomerular lesions were found: a thin basement membrane with fusion of foot processes suggestive of lipoid nephrosis and linear electron-density in the basement membrane with excessive mesangial matrix and capillary collapse suggesting an antibasement membrane type of glomerulonephritis or mesangial sclerosis. Conspicuous cystic spaces were found in the proximal tubules only. In the arterioles there were cystic spaces in the endothelial cells and smooth muscle cells, thickening of the basement membranes of endothelial cells and smooth muscle cells, and excessive amounts of nonstriated fibrils in the subendothelial basement membrane. Masses of fibrin were noted in the lumina of veins, peritubular capillaries, and interstitium between veins and peritubular capillaries. Such multiple glomerular and arteriolar lesions have not been reported previously in congenital nephrotic syndrome. These lesions suggest an antigen-antibody reaction in the mother that might have been directed toward the glomerular basement membrane in the fetus, producing these lesions.


Determination of prenatal sex ratio in man. The sex of a conceptus at the early embryonic state was diagnosed in 1000 induced abortions. Specimens were obtained from women who terminated their pregnancies within 12 menstrual weeks on socio-economic indications. By making use of the triple checking procedures, such as the karyotypic analysis of Giemsa-stained slides, the fluorescent Y chromosome analysis and the Y-body test in interphase nuclei, the sex ratio was determined as 106.6 (516 males/484 females). The sex distribution in the chromosomally normal embryos was 481 in males to 448 in females; that gave the ratio of 107.4. A slight excess of males was already present at his stage of pregnancy. When the ratios were calculated in relation to the maternal age, the lower sex ratio was noted for embryos born to mothers over 30 years. Taking a Y-bearing embryo as male, the ratio in 71 chromosomally aberrant embryos was 97.2 (35 males/36 females). The sex ratio in the cases of chromosome abnormalities was not statistically different from that of thenormal embryos.


Variants of galactose-1-phosphate uridyl transferase in the Greek populations. The frequency of variants of galactose-1-phosphate uridyl transferase was determined among the nine Greek populations by studying a sample of 1570 unselected individuals. Average frequency of normal allele GALT=0.942, galactosemia gen GALTG=0.0021 and the Duarte variant gene GALTD=0.0548 were observed. Frequency of galactosemia heterozygotes among Greeks was similar to that in other Caucasian populations, but the frequency of the Duarte variant was considerably higher. With the exception of two populations, one with low (Epirus) and one with high (Thrace) frequencies, the polymorphism of the Duarte variant displays very similar frequencies in the various Greek population groups.


Ring 11 chromosome (46,xx,r11(p15q25)).

Ring 11 chromosome (46,xx,r11(p15q25)). A girl has a stable chromosome 11, which does not reveal loss of any chromosomal material. She demonstrates small stature, mild retardation, behavior problems, mild abnormal EEG, prominent sole furrow, increased deep tendon reflexes and hypothyroidism; this latter condition may have contributed to her retardation.


Critical adjustment of cysteine and glutamine concentrations for improved clonal growth of WI-38 cells. Clonal growth of WI-38 cells with a plating efficiency of 45% has been achieved in a synthetic nutrient mixture (MCDB 102) supplemented with either whole or dialyzed fetal bovine serum precisely. Deviation by a factor of three in either direction from the optimum concentration (9.0 x 10(-5) M) eliminates essentially all clonal growth. A high concentration of glutamine (2.5 x 10(-3) M) is also needed for optimum clonal growth.


Organogenesis in in vitro cultures of embryonic shoots of Abies balsamea (balsam fir). Embryonic shoots of 15- to 20-year-old Abies balsamea (balsam fir) trees were soaked in (a) water for 15 min or 24 hr and (b) water with 1000 mg per 1 indolebutyric acid (IBA), N-dimethylaminosuccinamic acid (Alar-85), or 1-phenyl-3-methyl-5-pyrazolone (PPZ), singly or in combination with 100 mg per 1 caffeic acid, for 15 min. After the soaking, the embryonic shoots were transferred to a nutrient medium. Nonsoaked (control) embryonic shoots elongated and often formed a basal callus but never showed organogenesis. The soaked embryonic shoots formed new apical buds, with or without bud scales, adventitious dwarf needles or shoots, and root- and embryo-like structures. One of the embryos germinated and formed an irregular shoot. No differences were found between the various soak treatments, except that the 15-min water soak was ineffective. The 24-hr water soak was as effective as the 15-min growth regulator treatments.


Collagen prolyl hydroxylation in WI-38 fibroblast cultures: action of hydralazine. The action of hydralazine on collagen prolyl hydroxylation was studied in a cell culture system using WI-38 fibroblasts. The prolyl hydroxylation level was determined by a method involving the digestion of collagen by bacterial collagenase and the examination of specific peptides. The presence of low concentrations of hydralazine (0.2 mM) in both "young" and "old" fibroblast cultures strongly inhibited collagen prolyl hydroxylation. The degree of inhibition was greater in serum-deficient cultures. No significant improvement in the degree of hydroxylation was observed by increasing either ascorbate or iron levels in the hydralazine-containing cultures in which hydroxylation was inhibited. Some of the reported side effects of hydralazine seen in patients might be related to its inhibitory effects on mixed function oxidative (MFO) hydroxylation systems. While the ascorbate dependence of the prolyl hydroxylase system of WI-38 decreased with the "age" of the culture, hydralazine inhibition of hydroxylation was dramatic with cultures of all "ages".


In vitro culture of ovaries of a viviparous gall midge. Ovaries of the viviparous pedogenetic gall midge Heteropeza pygmaea can be cultured in hemolymph obtained from X-ray-sterilized larvae of the same species. In this culture medium, formation of follicles is essentially the same as in vivo, and sometimes female larvae develop from these follicles. The ovaries of such larvae, in their turn, have been cultured in vitro to produce larvae. In this way, in vitro development from oogonium to larva has been maintained for several generations. When using hemolymph obtained from larvae grown under different conditions, the in vitro cultured ovaries produce a second type of egg which probably is male-determined. Ovarian development in vitro has been studied with differential interference contrast optics and time-lapse cinemicrography.


[In vitro susceptibility of bacteroidaceae to cefoxitin and cephalothin (author's transl)]. The activity of the new cephamycin C derivatives cefoxitin against 102 clinical isolates of Bacteroidaceae (95 Bacteroides strains and 7 Fusobacterium-Sphaerophorus cultures) was determined by tube dilution and standardized agar diffusion tests and compared to that of cephalothin. Cefoxitin was more active than cephalothin against 56 Bacteroides fragilis strains, 19 Bacteroides thetaiota-omicron strains and two Bacteroides splanchnicus strains. The difference seemed less pronounced with five Bacteroides vulgatus and four Bacteroides variabilis cultures. Three Bacteroides melaninogenicus and six Bacteroides oralis strains displayed similar sensitivity to both cephalosporins. At concentrations of 32 microng/ml or less, cefoxitin inhibited 91% and cephalothin 33% of the Bacteroides strains. Two strains of Sphaerophorus varius were likewise much more sensitive to cefoxitin than to cephalothin (MIC values 8 micron8/ml of cefoxitin and 256 microng/ml of cephalothin). Three other Sphaerophorus strains (the species necrophorus and freundii/mortiferum) and two of Fusobacterium fusiforme (Fusobacterium nucleatum) strains were very similar in their susceptibility to both cephalosporins. Statistical analysis of the relationship between MIC and zone size diameter showed relatively high correlation coefficients for cefoxitin and cephalothin (r=-0.741 and r=-0.703 respectively).


[Asepsis and antisepsis in the treatment of burn patients (author's transl)]. Among the main aspects to be considered when treating burns, the problem of infection control remains unsolved. Considerable financial resources are needed to prevent the transmission of organisms. To justify such investments in buildings and antiseptic measures, an extensive epidemiological hospital study was carried out from 1970 to 1974, involving 930 patients, and more than 25,000 wound biopsies as well as 10,000 contact cultures and environmental swabs. Bacteria from the environment of severly burned patients were counted every week. Serotyping was used for a specialized study of Pseudomonas aeruginosa. In 200 patients wound organisms were counted. The most important organisms were: Streptococcaceae (pyogenic streptococci, less frequently faecal and salivary streptococci). Pseudomonadaceae, Enterobacteriaceae, and Micrococcaceae (especially Micrococcus aureus). Povidon iodine, gentamicin and silver sulfadiazine were used for local disinfection. Antibiotics used were gentamicin, carbenicillin and polymyxin. Whereas from 1970 to 1972 P. aeruginosa was the predominant organism found in wounds, other gram-positive organisms increased from 1972 on. Wounds were colonized mainly in the course of the first two weeks of treatment. Special studies regarding P. aeruginosa revealed a predominance of serotypes 5 and 13 between 1970 and 1973, whereas types brought into the hospital were dominant from 1973 on. An analysis of furniture and equipment, water faucets and drains showed that Pseudomonas strains found in the water did not coincide with those found in wounds. Therefore, a contamination from this source seems unlikely. Strains found on furniture and equipment, however, also appeared in the wound flora. When the therapeutic routine was changed (to prevent patients passing through common treatment areas such as bathrooms and dressing areas) hospital organisms 5 and 13 could be eliminated almost completely. Thus, it is possible to achieve a considerable reduction in the rate of cross-infection among patients by, for instance, excluding common treatment areas from the therapy programme. Nevertheless, in the majority of cases wounds will still be colonized, in particular by bacteria that were already in the anal region or on the skin before the patient was injured. For this reason, the elimination of such organisms by topical bactericidal agents constitutes an an important factor in efforts to reduce the rate of septicaemic complications. In view of the persisting high mortality due to generalized infections this therapeutic aspect must also be exploited thoroughly in the future. Although in comparative studies of topical therapy using povidon iodine, silver sulfadiazine and gentamicin, organisms did appear in the course of the first two weeks; in the case of the PVP-I the colonization never reached 10(5) organisms per cm2, i.e. the danger threshold for generalized sepsis. There was no evidence of a correlation between number of organisms and depth of burns.


[Early development of a child following rabies of the mother during pregnancy (author's transl)]. A case of rabies in a pregnant woman who spontaneously delivered a premature baby before dying is presented. Although not vaccinated the baby did not develop rabies. The possibility of displacental transmission of rabies in humans is judged  as highly improbable on the basis of findings in other publications and in the case presented here.


The mechanical properties of the respiratory system during anesthesia. 1. Static compliance of the total respiratory system is decreased during anesthesia, 2. The fall in total static compliance is probably caused by a fall in lung compliance. 3. It seems unlikely that the fall in lung compliance is the primary event. The change in pleural pressures at FRC before and during anesthesia would answer this question, but the data are conflicting. 4. It is more likely that the position of the chest wall pressure-volume curve shifts to the right as a consequence of anesthesia, so that the position of equilibrium for the lung and chest wall at FRC is at a lower volume. The alteration in the chest wall is possibly because of loss of respiratory muscle tone. 5. FRC is reduced. Gas trapping occurs as a secondary event if FRC falls to below CC. 6. Lung compliance falls as a consequence of the fall in FRC, but only if FRC drops below CC, and closure occurs. No data of the correlation of change in lung compliance to the relationship of FRC to CC have been published. 7. A-aDo2 increases because of an increase in the amount of lung where ventilation is reduced compared to perfusion. Areas of zero ventilation (shunt) will also be produced. 8. The changes in lung compliance, FRC, and A-aDo2 appear to have similar characteristics. They are not influenced by depth or type of general anesthesia or the presence of neuromuscular blockade. They appear as soon as anesthesia is induced and are not progressive with time during anesthesia. They are less in the sitting position and in taller, thinner subjects. They appear to be only transiently affected by hyperinflations. 9. The fall in total respiratory system compliance may contribute to the apparent depression of the ventilatory response to carbon dioxide.


Immunogenicity of p-phenetidine, 2-hydroxy-p-phenetidine and their protein conjugates in guinea pigs, rabbits and man. Guinea pigs were sensitized by p-phenetidine (PT), 2-hydroxy-p-phenetidine (HPT) as well as by conjugates prepared by reacting PT and HPT with proteins in vitro. Sensitization was evaluated by delayed skin reactivity and in vitro antigen-induced lymphocyte proleferation. HPT and HPT-protein conjugates were found to be the most effective sensitizing agents. Reaginic antibodies could be raised in both guinea pigs and rabbits by immunizing with PT- and HPT-protein conjugates but not by PT and HPT alone: these PCA antibodies showed strong cross-reactivity and could be elicited equally well with either  the PT- or HPT-protein derivatives. By contrast, no precipitating antibodies could be raised in either species even after repeated immunizations over a period of 4 months. Peripheral blood lymphocytes, from a few patients who gave a positive patch test with PT, could be stiumlated in vitro with phenacetin and to a lesser degree with PT and with a HPT-derivative of human serum albumin.


Cell-mediated and humoral immune responses in mice. II. Sensitizing conditions for delayed-type hypersensitivity. Conditions for the induction of delayed-type hypersensitivity (DTH) in mice to serum proteins ware studied. DTH to bovine serum  albumin (BSA) was induced by a subcutaneous immunizaiton with the antigen emulsified with Freund's complete adjuvant. The level of DTH was found to be dempendent not only on the dose of antigen but also on the amount of mycobacteria included in the adjuvant. DTH to other serum proteins was also induced under the same sensitizing conditions as for BSA. Success in the adoptive transfer with lymphoie cells and suppressive effect of anti-thymocyte serum indicated that delayed-type reaction studied here was the manifestation of cell-mediated immunity.


Experimental hypersensitivity pneumonitis: reduced severity of clinical response following repeated injections of Micropolyspora faeni antigen. Subcutaneous injection of soluble M. faeni antigen administered during a series of aerosol provocations to previously sensitized calves was found to diminish severity of clinical response. The mechanism by which response was reduced was not apparent.


Diagnosis of reaginic allergy with house dust, animal dander and pollen allergens in adult patients. III. Case histories and combinations of case histories, skin tests and the radioallergosorbent test, RAST, compared with provocation tests. Case histories alone and combined with the results of skin tests and/or the radioallergosorbent test (RAST) were compared with the results of provocation tests in 397 patients with asthma or allergic rhinitis. Case histories often turned out to be doubtful. The agreement between negative histories and negative provocation tests was 77% and that between positive histories and positive provocation tests 64%. When case histories were supported by concordant skin test or RAST results, the agreement with provocation tests increased to about 90%. When a scoring system for the combinations of different diagnostic methods was employed, a 100% agreement with provocation tests was obtained for cases with high scores. It is concluded that by using the case history in conjunction with RAST and/or skin test results, a reliable diagnosis can be achieved, eliminating the necessity of provocation tests.


Dissociation of blastogenic factor production and lymphocyte transformation of guinea pig lymphocytes stimulated with tuberculin PPD. In vitro lymphocyte transformation of guinea pig lymph node cells induced by tuberculin PPD was essentially eliminated by treatment with 5-bromo-2-deoxyuridine and light. The remaining cell population was still capable of producing blastogenic factor and further, the amount of blastogenic factor released was comparable to that from the intact population in the same interval of culture. This result favors the conception that cells producing blastogenic factor in response to antigen are distinct from the cells responding to the antigen by DNA synthesis and proliferation.


Statistical comparison of power spectra: a computer program. A general computer program, of interest to neurobiologists, for comparison of uncorrelated power spectra is presented. The program, ALPHAF, is written in Fortran V language and is easily compiled and executed in any computer with a Fortran software package. The purpose of the program is to read power spectral density (PSD) values into a computer from digital tape and then perform the following functions: (1) compute and report power; (2) compute and report averages of the computed power values over selected frequency bands and (3) compute and report statistical standardised normal distributions for a frequency spectrum of interest. The standardised normal distribution statistic is derived by using equation 7.20, page 250 of Random data: Analysis and measurement procedures (Bendat and Piersol, 1971).


A physical model of time-dependent flow in the human air passages. A physical model of the time-dependent, homogeneous, viscous and incompressible flow in the first twelve bronchial branches is described. The anatomical data given by Weibel (1963) are used. By means of these hypotheses we obtain the following equation: Palv(t) = K1V'B(t) + K2VB2'(T), where K1 and K2 are constants which depend on bronchial geometry and Palv(t) and VB(t) are the alveolar pressure and the mouth flow rate, respectively. Some results concerning laterobronchial pressure and velocities are given.


Influence of population on the classification of ECG-VCG's using linear regression techniques. This paper describes the influence of different populations on statistical multivariate classification rules and classification results where the word "population" refers only to the frequency of diagnoses to be expected, the so-called prior probabilities. Using linear regression as a multivariate classification technique and six groups consisting of five pathological conditions and normals as test data, it has been shown: (a) That the population influences to a great extent the selection of the best ECG-VCG measurements for the classification rule. (b) That a mismatch of the populations in the learning and test sets can considerably decrease the number of correct classifications. (c) That a certain correction of the mismatch can be achieved when the prior probabilities in the learning and test sets are known, Further, the paper discusses the change of prior probabilities over the years at the Variety Club Heart Hospital in the University of Minnesota and its effect on the performance of the classification algorithm which has been used.


A random walk model of cellular kinetics. The sorting out of biological cell mixtures into clusters of one cell type is modelled as a consequence of random cell and cluster motion, during which cells of like type cohere upon collision. After a description of the model and its motility rules, the results of several computer simulation studies are analysed and compared with both laboratory data and certain theoretical predictions. The model is found to be more biologically realistic than previous models with similar results. Suggestions for further reserach are discussed. An Appendix contains details about the data structures and algorithms employed in the simulation.


Semiautomatic processing of neurophysiological data: part II--a computer program for data reduction. This paper describes a program for the processing of trains of nerve or muscle impulses (spikes). The program is designed to allow the efficient use of semiautomatic or manual measuring devices. It will handle up to six different sets of spikes and one cyclic,non-spike event (e.g., changing light intensity or limb position, etc.) Output may include computed interspike intervals and instantaneous frequencies, phase relationships between sets of spikes and between spikes and the non-spike event, and parameters of bursts found in the spike trains. Output is presented numerically and in the form of line-printer graphs,


The epidemiology of drug promotion.

The epidemiology of drug promotion. A survey was conducted on the promotion of 28 prescription drugs in the form of 40 different products marketed in the United States and Latin America by 23 multinational pharmaceutical companies. Striking differences were found in the manner in which the identical drug, marketed by the identical company or its foreign affiliate, was described to physicians in the United States and to physicians in Latin America. In the United States, the listed indications were usually few in number, while the contraindications, warnings, and potential adverse reactions were given in extensive detail. In Latin America, the listed indications were far more numerous, while the hazards were usually minimized, glossed over, or totally ignored. The differences were not simply between the United States on the  one hand and all the Latin American countries on the other. There were substantial differences within Latin America, with the same global company telling one story in Mexico, another in Central America, a third in Ecuador and Colombia, and yet another in Brazil. The companies have sought to defend these practices by contending that they are not breaking any Latin American laws. In some countries, however, such promotion is in clear violation of the law. The corporate ethics and social responsibilities concerned here call for examination and action.


National health insurance policy in the United States: a case of non-decision-making. Despite the vast range of commentaries and research on the current health care crisis, little research attention has been focused specifically on the lack of federal response to this crisis. As a way of focusing analysis on the specifics of Congressional inaction, it is suggested that both the range of health care proposals and the current debates in Congress may be seen as part of an ongoing bargaining process over legitimate alternatives for modication of health care delivery. It is argued that the lack of any new health care legislation may be seen as the result of a series of non-decision by conservative Congressional representatives of the dominant medical interest groups. These non-decisions have successfully excluded any challenges to those interests by reliance upon a predominant "mobilization of bias" to effectively define and/or divert these challenges as illegitimate attempts at change. The changes which eventually evolve from Congressional compromise may represent a modification of the prevailing bias concerning legitimate alternatives, but are unlikely to modify the relation of the controlling interests involved.


Women in male-dominated health professions. Analysis of survey data on six health professions in Michigan suggests the extent to which sex-role stereotypes are reflected in the distribution of women within and among those professions which typically function as independent practitioners. The particular emphasis of the analysis is the structural or organizational aspects of the professions which facilitate or hinder the recruitment and participation of women. Distribution of women among professions is associated with relative levels of sex-segregation and with the relative availability of career opportunities in nonentrepreneurial settings. Implications of these findings for future trends in the sex structure of the health professions are discussed and a research agenda on women health professionals  is proposed.


"Thinking the unthinkable": the prospect of compulsory sterilization in India. The National Population Policy Statement adopted by the Government of India in April 1976 gave states the mandate to adopt coercive and compulsory sterilization measures toward the end of bringing under control the nation's massive population growth. Many states have since adopted stringent measures which penalize couples having three or more children, and four states additionally have proposed legislation for compulsory sterilization. While the demographic impact of compulsory sterilization after the third child is undisputed, the administrative feasibility of such and undertaking has been widely questioned, particularly in light of the inadequacy of India's medical infrastructure in the rural areas. Critics further have raised questions concerning the social  and ethical implications of compulsory sterilization and of measures which penalize the poor through means which may have adverse effects on their health and welfare. Finally, opponents of the new sterilization measures have suggested that they divert attention from the need for more basic changes in the nation's economic and social structure. While the need for bringing down India's continued high birth rate is widely recognized, alternative population measures-e.g. increased abortion facilities and an enforcement of the raised age at marriage-have been advocated in lieu of the compulsory sterilization measures currently being proposed.


Social class, political powere, and the state and their implications in medicine. This three-part article presents an analysis of the distribution of power and of the nature of the state in Western industrialized societies, and details their implications in medicine. Part I presents a critique of contemporary theories of the Western system of power; discusses the countervailing pluralist and power elite theories, as well as those of bureaucratic and professional control; and concludes with an examination of the Marxist theories of economic determinism, structural determinism, and corporate statism. Part II presents a Marxist theory of the role, nature, and characteristics of state intervention. Part III focuses on the mode of that intervention and the reasons for its growth, with an added analysis of the attributes of state intervention in the health sector and of the dialectical relationship between its growth and the current fiscal crisis of the state. In all three parts, the focus is on Western European countries and on North America, with many examples and categories drawn from the area of medicine.


Health indexes sensitive to medical care variation. Data from the fifteen Hospital Regions of England and Wales were used to determine the utility of health outcome indexes, derived from existing health statistics, for monitoring the quality and effectiveness of health services. Outcome measures reflect not only the impact of the system of care but also the sociodemographic characteristics of the population. An attempt therefore was made to identify those outcome measures most sensitive to variations in medical care and least affected by sociodemographic differences. In general, most indexes examined in this paper appear to be more sensitive to variations in the sociodemographic characteristics of the population. However, thosoutcome measures related to provision of care in hospital appear to relatively more sensitive to variation in medical care than those which are community based. This suggests that, at least for monitoring the effectiveness of medical care in the community, it may be necessary to move away from the more "traditional" health indexes toward measures that take into consideration the different patterns of care and the social and behavioral aspects of health.


Incontinentia pigmenti achromians (Ito's hypomelanosis). A 2-year-old Mexican girl had hypochromic lesions characteristic of incontinentia pigmenti achromians on the right half of the body. Extra cutaneous alterations were: dacryostenosis, bilateral genu valgus,ataxic gait, language retardation, hydrocephaly and abnormal electroencephalogram. Electron microscopy showed numerous Langerhans cells in the epidermis.


Some observations on the carbohydrate composition of purified transferrin. Five subfractions were isolated on DEAE-cellulose from samples of a commercially available human transferrin preparation and their carbohydrate composition was analysed. Hexosamine, galactose and total hexose were determined in four subfractions and sialic acid in all five. The data obtained indicate that the excess number of electrophoretic bands observed in transferrin from this source is due to the loss of carbohydrates which only affects sialic acid and none of the other sugar types. The availability of the penultimate galactose residues as the terminal residues in the subfractions deficient in sialic acid was also confirmed by a biological test utilizing the rat liver. The reason for the gradual loss of sialic acid from transferrin is unknown. Freezing-thawing and lyophilization did not detectably affect the sialic acid content of purified transferrin. However, free sialic acid did appear in some preparations on storage. It is concluded that similar changes in the carbohydrate composition of other plasma glycoproteins before, during, or after purification can be expected to exert an adverse effect on their usefulness as metabolic tracers.


Thermophilic aminopeptidase. IV. Cooperative effects in ANS binding by the thermophilic aminopeptidase I from B. stearothermophilus. Aminopeptidase I is a membrane-bound metalloenzyme isolated from B. stearothermophilus which is thermostable and requires Co2+ for activity. The Co, Zn, and metal-free enzyme were titrated with ANS, and cooperative binding was noted with the active Co enzyme but not with the Zn (5% active) or apo (inactive) enzymes. There are a number of sites for ANS on each of the three enzyme forms and the agreement between the association constants of the Zn enzyme (identical and independent sites) and the non-cooperative sites of the Co enzyme suggest that these sites are intrinsically similar. However, binding to the first of these sites in the Co enzyme triggers a cooperative binding of a second molecule of ANS, and this cooperative binding is related to a concomitant decrease in enzymatic activity. The correspondence can be shown by comparison of the inhibition constant for the hydrolysis of Gly-Leu-Tyr (Ki-1=13,300 cm3/mmol) and the association constant for the cooperating site (12,500 cm3/mmol). The significance of these observations is discussed in terms of the nature of the binding sites and the possible consequences of the interactions on the regulation of aminopeptidase I activity.


Conformational studies on cyclic dipeptides. An analysis of 11 crystal structures of cyclic dipeptides so far reported in the literature is made, with main reference to the internal parameters of these molecules. Preferred conformations of the side chains of cyclic dipeptides with different alpha-amino acid residues have been studied by classical energy calculations. The possible conformations of the DKP ring are also studied. The significance of the non-bonded interaction in deciding the pathway for conformational change has also been investigated. The agreement between theoretical results and experimental observations is quite good, both with respect to the conformation of these molecules as well as the enthalpy difference as estimated from n.m.r. studies between different conformers.


Controversies and realities of therapy for varicosis. Proponents of surgical eradication of varicose veins claim a high cure rate. Proponents of the conservative methods of multiple injections of sclerosing agents claim that this money-saving ambulatory method avoids hospitalization and loss of working time, that the end results are quite satisfactory and that any recurrences can be easily dealt with by reinjections. Both methods are effective. Both have their indications. Many surgeons use sclerotherapy after surgery as complementary therapy. Radical views recommending surgery or injections exclusively are contrary to the principles of good medical care and do injustice to the patient. A simple venographic technic demonstrating the status of the greater saphenous veins is described.


Serum immunoglobulins after surgical operations. Serum concentrations of IgG, IgM and IgA were determined before and after surgery in 38 patients Eighteen patients who were anesthetized for less than 2.5 hours showed a slight decrease of serum IgG levels on the first and third postoperative days. The fall in serum levels of IgG on the first and third postoperative days was significant in 20 patients who underwent surgical operations which lasted more than 2.5 hours. Serum IgM increased on the third and seventh postoperative days. Alterations of IgA levels were minimal. The incidence of postoperative surgical infection was much higher in the group of patients which had lengthier operations. Though the number of patients was small for statistical evaluation, a correlation was observed between serum levels of IgG and IgM and the risk of developing surgical infection. Possible mechanisms underlying these changes in serum immunoglobulins are briefly discussed. We suggest that the duration of exposure to an anesthetic agent may be more important than the severity of surgical trauma in causing alterations of serum immunoglobulins.


Improving diagnostic accuracy: a comparison of interactive and Delphi consultations. Consultation among physicians on difficult diagnostic problems is commonly used to improve the accuracy of medical decisions. Such consultation is most often informal and interactive. Nevertheless, behavioral studies suggest that non-interactive techniques may be more effective problem solving methods. Of these the Delphi approach, involving pooling and feedback of anonymously contributed information, has generated particular interest. To assess the relative effectiveness of independent decision making, interactive group consultation, and Delphi techniques in a clinical setting we compared the diagnostic accuracy of 17 radiologists interpreting radiologic examinations in these settings. Interactive consultation improved performance by 69% compared to radiologists interpreting the studies individually. In addition, two Delphi strategies each produced an additional 20% mean improvement in accuracy over interactive consultation. Whereas interactive consultation improved the accuracy of the best individual readers by only 6%, a Delphi model improved their performance by 25%. Thus, Delphi was an effective, easily applied method of clinical consultation whose usefulness in other clinical setting should be evaluated.


Comparative efficacy of coronary vasodilatory methods. The relative efficacy and sequelae of several coronary vasodilator methods were compared in dogs. Maximal coronary vasodilation with least apparent side effect was achieved with infusion of adenosine triphosphate (ATP) at the rate of approximately 600 microng/minute (approximately 20 microng/kg/minute). This method increased conductance to 7 to 8 times control levels and may have fully depleted vasodilator reserve. Bolus injections of ATP or papaverine alone increased conductances three to four fold and approximated the effects of 15 seconds of occlusion of the circumflex coronary artery. Duration of effect was variable. Diatrizoate injections were somewhat less effective vasodilators and produced greater electrocardiographic and systemic effects. Bolus injections of mixtures of ATP and papaverine demonstrated additive effects, and increased conductance 5 to 6 times control levels. In further exploring the diagnostic value of vasodilatory redistribution of myocardial blood flow or appearance of collateral circulation as a sign of a hemodynamically significant stenosis, selective intracoronary infusion of ATP is a promising vasodilatory method.


Transcatheter electrocoagulation: a therapeutic angiographic technique for vessel occlusion. Previous work has shown that localized electrocoagulation of blood vessels using direct current applied by catheter placed electrodes is feasible. In vitro and in vivo experiments showed that clot size and thrombosis of vessels are directly related to the product of the amount and duration of the current. Surgically created splenic hemorrhage was well controlled in 9 of 10 animals. The vessels remained permanently occluded after electrocoagulation in 8 of 9 animals. Pathological studies of all the vessels showed intimal damage at the sites of occlusion. These experiments indicate that clot formation may be a product of both intimal damage and platelet attraction to the positive electrode. The technique has advantages over embolization since no foreign material is injected and a localized clot is produced at the tip of the guidewire. There are certain disadvantages and further refinements must be developed to establish transcatheter electrocoagulation as a useful clinical technique for vessel occlusion.


Aerobic work capacity in sedentary men and active athletes in Israel. Maximal oxygen uptake (Vo2max) was estimated in 1,200 sedentary men aged 18 to 50 years and in 400 active athletes aged 18 to 30 years participating in 10 different kinds of sport. The Vo2 in the 18- to 30-year-old sedentary group was 34.3 +/- 9.7 (SD) ml - kg-1 - min-1, and in the 31- to 40- and 41- to 50-year age groups a similar value of 28.1 +/- 9.9 ml - kg-1 - min-1 was recorded. The results in the sedentary group were lower than those recorded in active populations in other countries by 20 to 40%, possibly due to lack of physical activity. The mean Vo2max in 400 active athletes was 54.8 +/- 10.0 ml - kg-1 - min-1, which is very similar to Vo2max values recorded in active populations in other countries. The difference between the mean Vo2max of the 18- to 30-year-old sedentary group and that of the active one was found to be signifcant (P less than 0.005). The highest mean Vo2max values among the athletes were recorded in the group of long-distance runners (60.8 ml - kg-1 - min-1) and cyclists (61.9 ml - min-1), while unexpectedly low mean Vo2max values were recorded in the group of swimmers (50.1 +/- 8.1 ml - kg-1 - min-1) and football players (51.7 +/- 9.1 ml - kg-1 - min-1).


Aerobic work capacity in high school students in Israel. Maximal oxygen uptake (Vo2max) was predicted in 1,951 high school students aged 14 to 19 years--1,061 girls and 890 boys--from five different types of high school. The schools represented most of the ethnic groups. The mean Vo2max in the boys was 41.3 +/- 9.4 (SD), and in the girls, 34.7 +/- 10.1 ml - kg-1 - min-1; it was highest at the age of 16 in the boys, and at ages 14 and 15 in the girls. Significant ethnic differences in Vo2max were recorded; Vo2max was highest in students of Middle Eastern and North African origin [boys 42.7 +/- 9.3 (SD), girls 35.9 +/- 14.5], and lowest in the subjects of European and North American origin (boys 39.8 +/- 9.2, girls 33.2 +/- 9.3). Israel-born students showed average values (boys 40.7 +/- 9.6, girls 35.2 +/- 10.9). Significant differences in mean Vo2max values were observed in the general and agricultural high schools, and the lowest values in boys were oberved in the heshiva (parochial) high school, and in girls in the state religous high school. The differences in Vo2max in the various subpopulations in Israel can be attributed mainly to different patterns of physical activity and in part to ethnic origin.


Urographic excretion studies with metrizamide and "Dimer": a high dose comparison in dogs. Metrizamide, a new non-ionic, triodinated contrast agent has been considerable for intravenous urography. Theory predicts that lower osmotic diuresis with this agent should lead to higher urinary iodine concentrations than with ionic agents, at equivalent iodine doses. However, a distinct advantage with metrizamide has not been observed with doses of 175 mgI/kg or less. In this study metrizamide and sodium locarmate were given intravenously to dehydrated dogs at a dose level of 600 mgI/kg. During the studies the concentrations and outputs of major urinary solutes were compared. Comparisons of urinary iodine concentrations and outputs showed that at this dose the predicted advantage with metrizamide can be observed.


Saturation kinetics of iodipamide.

Saturation kinetics of iodipamide. To characterize the saturation kinetics of iodipamide, timed samples of blood, urine, and bile were taken from two unanesthetized dogs infused with iodipamide at increasing rates to achieve various steady state blood concentrations. Biliary excretion rate of iodipamide reached an asymptote with increasing blood concentration, indicating a biliary transport maximum (Tm) of 15.2 to 16.2 mgI/min. Urinary excretion was not a pure, first order process and urinary excretion rate was higher than the glomerular filtration rate corrected for plasma protein binding, suggesting that active tubular secretion may play a part. Extrarenal elimination followed Michaelis-Menten kinetics. Estimates of maximum rate (Vm) and Michaelis-Menten constant (Km) were obtained graphically. The estimated values of Vm were 4 to 6 times that of biliary Tm. In acute infusion experiments the iodipamide excreted in the bile and urine and that remaining in the organs analyzed accounted for only a fraction of the dose administered; no significant accumulation of iodipamide was found in the liver.


Expimental segmental replacement of esophagus by biological tissues. A method is described for segmental esophageal replacement in dogs, with one of three types of tissue substitute: pericardium, fascia lata and aortic homograft. The experiments involving the thoracic esophagus failed owing to the development of acute mediastinitis and sepsis. The most promising results were obtained in animals in which an aortic homograft was used to replace the cervical sigment of the esophagus. Eight of the 12 animals with aortic homograft survived and gained weight until killed one to six months after operation. The overall results suggest that aortic homograft may have a potential clinical application in cases in which esophageal replacement is necessary.


Dichromatic absorptiometry of vertebral bone mineral content. A dichromatic photon absorptiometric technique for the in vivo measurement of the bone mineral of the spine is discussed. A high purity, high activity 153Gd source which has photons of predominantly 44 and 100 keV was used as the transmission source. The transmission scans were performed on a modified Ohio Nuclear whole body rectillinear scanner. The precision of four measurements on three individuals and three measurements on one individual over a one month period was 2.3% (coefficient of variation). The accuracy determined by measurements of phantoms with known concentrations of dipotassium hydrogen phosphate solutions was 1.2% (standard error of estimate). This technique can be applied in most well equipped nuclear medicine departments.


Localization of the conduction delay occurring during coronary arteriography. The effect of coronary arteriography on intraventricular conduction was studied in 12 atropinized, open-chest dogs. Left bundle-branch (LB) and cavitary (V) potentials were recorded from a bipolar electrode catheter positioned against the septum below the aortic valve. Subendocardial (SEE) and subepicardial (IME) bipolar potentials were obtained from distal and proximal poles of multipolar electrode needles. Conduction times from LB to V, LB or V to SEE and SEE to IME were obtained during control and during Renografin 76 (REN) and normal saline injections into the left and right coronary arteries. Significant QRS axis changes and increased QRS duration occurred in 6 of 12 dogs simultaneously with LB-SEE and V-SEE delay. In 6 without axis changes, REN produced significant delay and increased QRS duration. Only REN to LCA produced significant changes. Coronary arteriography alters conduction through the distal left ventricular Purkinje system without affecting transmural conduction.


Salt conservation in familial dysautonomia (Riley-Day syndrome). In some patients with familial dysautonimia, plasma renin activity shows a paradoxical response to postural stimuli, i.e., levels of plasma renin activity are high when the patient is in the supine position and fall significantly during subsequent ambulation. Furthermore, there is no coordinated release of plasma renin activity and aldosterone. The aim of the present study was to determine whether these findings are accompanied by a disturbance of salt conservation. Six patients were studied in a summer camp while on normal and low-salt diets. Plasma and urinary aldosterone levels rose sharply and appropriately when four of the patients were placed on a low-sodium diet. In these subjects, urinary sodium output fell sharply although three of them failed to attain sodium equilibrium by the third day of the low-sodium regimen. Elevation of early morning plasma renin activity appeared to correlate with an inversion in the normal day-night rhythm in urinary volume.


Estimation of chemical composition and density from computed tomography carried out at a number of energies. A method is presented by whichcomputed tomography scans carried out at a number of energies may be utilized to obtain cross-sectional images of density and atomic number in addition to the conventional array of linear attenuation coefficients. This type of analysis has been carried out for various substances of biological relevance. Computer simulated reconstructions of clinical situations suggest that the method shows promise for providing additional diagnostic information and might dispense to some extent with the necessity of injecting contrast agents into the patient.


The influence of film density on the radiologic detection of lung lesions. Experiments were conducted on a series of chest radiographs to evaluate the effects of mean film density on reader performance. It was found that the false negative is not measurably affected, in agreement with earlier published data. It was also found, however, that the false positive rate increases with increasing film density. The causes and implications of these results are discussed.


Near drowning in the Dead Sea.

Near drowning in the Dead Sea. Seven cases of submersion in the Dead Sea are described. The clinical picture varied in severity and consisted of signs of pulmonary edema, chemical bronchitis, hypermagnesemia and hemoconcentration. Two of the patients died of hypotension and cardiac arrhythmia. The clinical findings were similar to those found in cases of drowning in seawather, but the presence of hypermangesemia is unique to this entity. The amount of aspirated water causing severe clinical signs seemed to be much smaller than is seen with ordinary seawater. Therapeutic guidelines, including assisted respiration, infusion of hypotonic solutions and corticosteroid therapy, are suggested.


Incidence of malignancy in Jewish women with postmenopausal bleeding. Postmenopausal bleeding is associated with a relatively high incidence of malignancy. The lowest incidence reported in the literature was observed among Jewish women in Jerusalem, more than 21 years ago (1). A similar survey of Jewish women admitted to our Department for postmenopausal bleeding during 1962-74 is presented. Fifty-five of 397 cases (13.8%) of postmenopausal bleeding were due to malignancy. There were 34 women with endometrial carcinoma, 11 with cervical carcinoma, five with ovarian carcinoma, four with uterine sarcoma and one with vaginal sarcoma. In 86% of cases, benign pathological states were found, 42.8% being associated with atrophic endometrium. An active endometrium was found in 56 patients (14%), and in two of them the endometrium was secretory. Estrogen therapy was not an important causative factor in these cases. The low incidence of malignancy seems to be due to the fact that cervical carcinoma is less common among Jewish women. Nevertheless, 20% of the malignant tumors in this series were invasive epidermoid carcinomas of the cervix. The need for a cytologic screening program in this country must therefore be reevaluated.


Retroperitoneal dissection of a pancreatic pseudocyst to the left inguinal region. We describe a patient in whom retroperitoneal dissection of an infected pseudocyst of the pancreas into the left inguinal region imitated an incarcerated hernia. The high level of diastase (32,000 units/ml) in the fluid from the inguinal region and the roentgenologically demonstrated communication between the pancreas and the left inguinal region proved that the source of the fluid was the pancreas. The appearance of a mass in the inguinal region in an alcoholic patient who has recently had pancreatitis should arouse suspicion of an origin in a dissecting pseudocyst of the pancreas.


[Significance of hair root status method]. The significance of proposition of the hair root status method is reported. The percentage composition of the hair root patterns of neighboring areas of the capillitium and the behavior of the percentage of the individual hair root shapes were examined at time zero and four weeks later. These examinations were carried out in the frontal, parietal and occipital regions of each of 10 male test persons with clinically normal hair growth and statistically evaluated by means of the multi-variate Hotelling T2 test [8]. The hair root pattern of neighboring areas is the same within the different regions of the capillitium (p less than 0.05). Thus the hair root patterns investigated in the different regions of the capillitium are representative of this respective region. The hair root patterns of males with clinically normal hair growth (for the frontal, parietal and occipital region) does not differ with time (p less than 0.05). Therefore, examination of the hair root pattern at four week intervals can be used for controlling the hair growth capacity and therapeutic effects. The significance of the hair root status method for controlling therapeutic effects may be relative small in the individual case in a person with normal hair growth, but useful when evaluated in a collective of subjects.


[Syphilis therapy--results of an inquiry]. In order to get some more information about the kind of treatment of syphilis in the F.R.G. a study among the 1578 practising dermatologists (without members of hospital staff) by means of questionaires was made. 1164 (79%) answered the inquiry. The study shows that nearly 50% of the answering dermatologists treat syphilis by several series of penicillin applications. On the other side, only one third of the respective dermatologists performs treatment by one series, giving penicillin from 15 to 21 Mega units. The study shows that the kind of therapy is rather age-dependend insofar as the older dermatologists prefer the multiple therapy series scheme, whereas the younger dermatologists are inclined to use the single series scheme. Furthermore geographical differences could be shown, e.g. most of the Bavarian dermatologists use the single series scheme. The kind of penicillin, way of application and the time intervals were rather uniform related to regions and schemes of therapy. Tetracycline and Erythromycin are used in case of penicillin allergy. In the opinion of less than 50% of dermatologists additional redications are necessary, whereby the younger ones prefere corticosteroides, the older ones potassium iodide. The benefits of uniformly performed therapy of syphilis by the single series scheme are discussed.


Congenital hypopituitarism associated with neonatal hypoglycemia and microphallus: effect of GH therapy. A case of congenital hypopituitarism with microphallus and severe neonatal hypoglycemia is described. The results of the clinical examination and of the tests of hypothalamo-pituitary function are discussed. It is reported that with GH replacement therapy a considerable growth of the penile size was obtained. The importance of evaluating the pituitary function in patients with micropenis and neonatal hypoglycemia is emphasized.


[Hemihypertrophy, nevus sebaceous, multiple bone cysts and cerebroretinal angiomatosis: a complex phakomatosis]. Report on a girl, who died at the age of 6 1/2 years having exhibited different dysplasias which are characteristic features of several phakomatoses: congenital cutaneous pigmentations, fibrolipoma of the scalp, hypertrophy of the right leg, multiple cysts of the long bones (fibrous dysplasia), and an aneurysma racemosum of the retina and mid-brain (syndrome of Bonnet-Blanc-Dechaume).


Haematological studies in a case of oculocerebrorenal syndrome. A four-year-old boy affected by oculocerebrorenal syndrome had moderate anaemia. The haematological study indicated hyperhaemolysis probably due to an extra-erythrocytic factor. It is suggested that this factor might be related to the metabolic disturbance of the disease, particularly the hyperchloraemic acidosis.


[Observations on the accent-method of Smith in the management of speech and voice disturbances. Part I (author's transl)]. One of the best known methods in northern Europe for the treatment of voice disorders is the "accent-method", which was devised by Svend Smith in Denmark. The method is based on the use of the stressed ("accentuated") syllable as a therapeutic tool to develop pronunciation and a natural attractive voice. Present theories of the physics and the physiology of voice function form the basis for the method, in addition to concepts from modern psychology and pedagogics. By using the technique, it is possible to develop a therapeutic field between patient and therapist within which voice and speech behavior can be treated as a whole. The method is described in detail in the present paper. In a forthcoming paper, the method will be discussed from the viewpoints of the physics and physiology of phonation as well as from pedagogical and psychological aspects,


[A comparison of the results of incus interposition in the Wullstein type III and type IV tympanoplasty (author's transl)]. Incus interposition for reconstruction of the sound conduction mechanism in a deep tympanic cavity can be effectively utilized in both Wullstein Type III and IV tympanoplasties. In the Type III tympanoplasty, in which the incus is interposed between malleus or tympanic membrane and stapes, the average post-operative air-bone gap approximates 16 db, while incus placement on the stapes footplate results in an air-bone gap of 23.5 db. There is no difference in change of bone conduction when all operative mehtods are compared. Improved results in reconstruction of the second conduction mechanism are best obtained by conserving or reconstructing the tympanic membrane and posterior bony external canal wall through improved audio-physiologic dynamics.


[On the pathogenesis of the Küttner tumor of the submandibular gland -- Analysis of 349 cases with chronic sialadenitis of the submandibular (author's transl)]. In view of the etiology and pathogenesis of the so-called Kütter tumor (chronic sialadenitis of the submandibular gland) gland resections of 349 patients (salivary gland register at the Institute of Pathology, University of Hamburg; period 165--1974) were analyzed pathohistologically. In 143 cases (41%) a sialolithiasis of the submandibular gland occurred simultaneously. Regarding the degree of the inflammation 4 stages were distinguished (stage 1 = focal sialadenitis; stage 2= diffuse lymphocytic sialadenitis with salivary gland fibrosis; stage 3 = chronic sclerosing sialadenitis with salivary gland sclerosis; stage 4= chronic progressive sialadenitis with salivary gland cirrhosis). Twenty-five per cent of the cases were classified in stage 1, 19% in stage 2, 38% in stage 3, and 18% in stage 4. A predominance of the male sex (70%) was observed especially in stage 4. The initial stage is characterized by a periductally lymphocytic infiltration, ectasias of the ducts, and alteration of the secret in the duct lumens (spheroliths, microliths). In stages 2--3 an increase of the inflammatory infiltration with lymph follicles, considerable alterations of the ducts (metaplasias, dysplasias, regenerates of the ducts), and a parenchymal reduction were found. This process is combined with an increase of the interstitial connective tissue and a cicatrication of the salivary gland parenchyma. In the final stage, 4, a cirrhotic gland transformation with progressive loss of the parenchyma and considerable duct destruction appeared. From the pathogenetic course of the inflammation and the comparison with other forms of sialadenitis, the conclusion is drawn that two etiologic factors are important in the Küttner tumor: an initial disturbance of secretion with an obstructive electrolyte sialadenitis and an immune reaction of the salivary duct system with the final phase of an obstructive, progressive immunosialadenitis.


A sodium sulfite-precipitation tests for assessment of colostral immunoglobulin transfer to calves. A sodium sulfite-precipitation test utilizing 3 concentrations of sodium sulfite to evaluate the immune status of neonatal calves allowed scoring of serum immunoglobulin concentrations as less than 5 mg/ml, 5 to 15 mg/ml, and greater than 15 mg/ml. Of the 54 estimations for serums that contained greater than 5 mg/ml, 96% were correct; of the 30 estimations for serums that had between 5 and 15 mg/ml, 90% were correct; and of the 42 estimations for for serums with greater than 15 mg/ml, 93% were correct. It was concluded that this test can be used under field conditions to evaluate the immune status of neonatal calves.


Relation between formant frequencies and optimal octaves in vowel perception. The purpose of this study was to investigate the relation between the traditional concept of formant frequencies and the controversial concept of optimal octaves in the perception of the vowels/i, a, u/. The vowels (produced by a male speaker of General American English) were filtered through eight bandwidths (80-160, 160-315, 315-630, 630-1,250, 1,250-2,500, 2,500-5,000, 5,000-10,000, and 10,000-20,000 Hz) and presented to two groups of subjects. One group performed similarity ratings on pairs of filtered and nonfiltered stimuli; the other identified the individual filtered and nonfiltered vowels. The optimal bandwidths derived from the data of the two groups were compared to the formant frequencies of our speaker, to those reported in the literature, and to the optimal octaves published earlier by other authors. The results showed that there were specific bandwidths which allowed for correct perception and identification of each vowel, and that these bandwidths were compatible with both the optimal octaves and the formant frequencies reported in the literature for each vowel.


Echocardiography in the horse.

Echocardiography in the horse. Echocardiograms were obtained from 25 standing, clinically normal horses, using an ultrasonic recording device. The echobeam penetrated the right thoracic wall in the area of the 4th to 5th intercostal space, with a frequency of 2.5 mHz. Measurements of left ventricular wall thickness generated a mean value of 3.2 +/- 0.18 (SEM)cm, whereas the left ventricular chamber diameter in diastole was 9.3 +/- 0.30 cm and in systole was 5.7 +/- 0.23 cm. The aortic root dimensions had a mean of 7.7 cm, with a SEM of 0.16. Mitral valve closing slope (E-F) was calculated to be 17.7 +/- 0.87 mm/second, and percentage of delta D, a correlate of ejection fraction, was 38.6 +/- 1.6%.


Identification of vowels with equated intensity. A preliminary study. The ability of listeners to identify 10 vowels under two conditions was investigated. In both conditions the vowels were presented at a comfortable loudness level in a constant phonetic environment with equal stress. In the first condition, the vowels were presented with their natural intensity differences, and in the second condition they were presented with their intensities equated. The role of relative intensity differences for the identification of vowel sounds at various loudness levels is discussed, and the likelihood that intensity differences play a more important role in identifying those vowel sounds having similar characteristics (i.e., formant frequencies ranges) is considered.


Effect of age and sex on the prevalence of intestinal parasitism in dogs. The effects of age, sex, and neutering on the prevalence of canine intestinal parasitism were evaluated by fecal examination of 1,468 pet dogs admitted to the University of Missouri Veterinary Teaching Hospital during 1975. Evidence of hookworm infection was encountered in 35.8% of the dogs examined, whipworms in 18.5%, ascarids in 17.9%, tapeworms in 5.2%, and coccidia in 4.5%. Evidence of intestinal parasitism was not detected in 653 (44.4%) dogs. Whipworm infections were detected less often in young dogs than in older ones, whereas ascarid and coccidial infections were more prevalent in pups that in mature dogs. In dogs more than 6 months old, hookworm infections were the most common parasitism. Tapeworm infections were diagnosed sporadically in all age groups. For most of these parasites, castrated males and spayed females had decreased prevalence of infection, compared with their respective intact counterparts. There were significant (P less than 0.05) differences in the prevalence of both ascarid and hookworm infections between intact and spayed female dogs. Also, there were significant (P less than 0.001) differences between age categories for all parasites observed. Overall, parasitism tended to decrease with age.


Brainstem wave V latencies to tone pip stimuli. The present study was undertaken to examine the feasibility of using tone pip stimuli rather than conventional clicks in brainstem evoked response (BER) audiometry. Trains of 2000-Hz tone pips, 4000-HZ tone pips or clicks were presented at seven intensity levels to six normal young adults. Results demonstrated that BERs can be readily elicited by tone pips. This latter finding may be attributable to the differences in stimulus rise times. Tone pips appear to introduce greater frequency specificity to BER audiometry without a marked loss in the ability to elicit the response.


Word discrimination in the presence of competing speech with children. This study was conducted to examine the auditory masking effects of classes of linguistic strings varying in syntactic and semantic constraints upon word discrimination abilities of children. Twelve fourth grade (age 9), normal hearing, native speakers of English served as subjects. Three half-lists of the Central Institute for the Deaf W-22 word lists were presented consecutively with one of three competing linguistic messages. Discrimination scores served as measures. A treatment-by-subject analysis of variance and t-tests for independent samples were used in the analysis of the data. No significant differences in word discrimination as a function of linguistic masker were found. Comparisons between the data obtained with the children of the present study and that of adult subjects of a similar investigation (Percept. Mot. Skills 41, 578-593, 1975) indicated no significant difference in mean discrimination scores under the grammatical and semantically anomalous conditions; however, significance was found for the ungrammatical masker. Selective listening and language processing were used in the discussion of the findings


Transport of urea at low concentrations in Chlamydomonas reinhardi. Urea transport into the unicellular green alga Chlamydomonas reinhardi was investigated to further our understanding of controls operating on urea catabolism in this organism. Transport into cells grown with acetate and deprived of ammonia is a saturable process, mediated by at least two systems operating maximally at different external urea concentrations. The lower concentration system, with an apparent Km for urea of 5.1 micron, was the object of detailed study. Transport of urea from a saturating concentration (57 micron) into ammonia- and acetate-grown cells freshly suspended in ammonia-limited medium was not detected. Upon further culturing in the absence of ammonia, derepression occurred with transport ability, first appearing at about 1 h , reaching a maximum at about 2 h, and maintaining this maximum at least 5 h. In contrast to this, CO2-grown cells became derepressed more slowly, and maximum transport ability was not maintained. Addition of ammonia or methylamine (5 mM) during nitrogen deprivation prevented further increases in transport ability and caused loss of previously acquired transport ability. Cycloheximide (10 microng/ml) had a similar effect. Energy uncouplers or dark, anaerobic conditions depressed transport. By these criteria, transport from low urea concentrations is mediated by a process that requires protein synthesis and activation by cellular energy, and the process has a rapid rate of turnover and of deactivation by ammonia.


Cell surface topography of Candida and Leucosporidium yeasts as revealed by scanning electron microscopy. The cell surface topography of the following yeast strains was examined by scanning electron microscopy: Candida slooffii, C. lipolytica, Leucosporidium frigidum, and L. nivalis. Multipolar and lateral budding were observed in the Candida yeasts in contrast to bipolar budding in the Leucosporidium species. The cell surface topography and the morphology of the bud and birth scars in these yeasts differed markedly. Apart from the bud and birth scars, the cells of C. slooffii showed a relatively smooth topography. The bud scars were seen as a circular ridge of wall material surrounding a markedly convex scar plug. Birth scars were raised, rounded structures, which appeared to distend upon cell growth. In contrast, bud scars of C. lipolytica were platelike, lacked a distinct annulus of wall material, and were much less protuberent than those of C. slooffii. Birth scars were a more permanent feature of these cells. The topography of Leucosporidium yeasts was characterized by the presence of numerous protrusions on the cell surface. In some cases, the entire cell surface was covered by these protrusions. There appeared to be some correlations between the age of the cell and the extent of surface protrusions and degree of surface convolution...


Third system for neutral amino acid transport in a marine pseudomonad. Uptake of leucine by the marine pseudomonad B-16 is an energy-dependent, concentrative process. Respiratory inhibitors, uncouplers, and sulfhydryl reagents block transport. The uptake of leucine is Na+ dependent, although the relationship between the rate of leucine uptake and Na+ concentration depends, to some extent, on the ionic strength of the suspending assay medium and the manner in which cells are washed prior to assay. Leucine transport can be separated into at least two systems: a low-affinity system with an apparent Km of 1.3 X 10(-5) M, and a high-affinity system with an apparent Km of 1.9 X 10(-7) M. The high-affinity system shows a specificity unusual for bacterial systems in that both aromatic and aliphatic amino acids inhibit leucine transport, provided that they have hydrophobic side chains of a length greater than that of two carbon atoms. The system exhibits strict stereospecificity for the L form. Phenylalanine inhibition was investigated in more detail. The Ki for inhibition of leucine transport by phenylalanine is about 1.4 X 10(-7) M. Phenylalanine itself is transported by an energy-dependent process whose specificity is the same as the high-affinity leucine transport system, as is expected if both amino acids share the same transport system. Studies with protoplasts indicate that a periplasmic binding protein is not an essential part of this transport system. Fein and MacLeod (J. Bacteriol. 124:1177-1190, 1975) reported two neutral amino acid transport systems in strain B-16: the DAG system, serving glycine, D-alanine, D-serine, and alpha-aminoisobutyric acid; and the LIV system, serving L-leucine, L-isoleucine, L-valine, and L-alanine. The high-affinity system reported here is a third neutral amino acid transport system in this marine pseudomonad. We propose the name "LIV-II" system.


New R plasmid-mediated restriction-modification system of deoxyribonucleic acid conferred by group E R plasmids. A new R plasmid-mediated restriction-modification system of deoxyribonucleic acid was identified. This system is specific for group E plasmids which have been detected in unidentified marine Vibrio fish pathogens.


Phospholipid and fatty acid composition of methanol-utilizing bacteria. Differences in phospholipid and fatty acid composition were found among bacteria using the serine or the ribulose monophosphate pathway for the assimilation of C1 compounds. These differences might be used as an additional criterion for the classification of methanol-utilizing bacteria.


Occurrence and nature of chromatic adaptation in cyanobacteria. Forty-four axenic strains of cyanobacteria that synthesize phycoerythrin were screened to ascertain the effect of light quality on pigment synthesis. Cellular pigment compositions were determined after photoautotrophic growth with low light fluxes (7.0 X 10(2) ergs/cm2 per s) of green, red, and white light, and in the case of facultative heterotrophs, after dark growth at the expense of sugars. Twelve strains did not adapt chromatically: the cells contained fixed proportions of phycoerythrin, phycocyanin, and allophycocyanin under the growth conditions used. In the remaining strains, the cellular ratio of phycoerythrin to phycocyanin was much higher after growth in green than in red light. Quantitative data on the cellular pigment contents, supplemented by measurements of the differential rates of pigment synthesis on representative strains, show that chromatic adaptation may involve a light-induced modulation either of phycoerythrin synthesis alone (7 strains) or of both phycoerythrin and phycocyanin synthesis (25 strains). Facultative hetrotrophs able to adapt chromatically have a phycobiliprotein composition after dark growth which closely resembles that after growth in red light. Light quality does not affect the differential rate of chlorophyll synthesis. The physiological and taxonomic implications of these findings are discussed.


Heterogeneity and refined structtures of 3-O-methyl-D-mannose polysaccharides from Mycobacterium smegmatis. The 3-O-methyl-D-mannose-containing polysaccharide (MMP) from Mycobacterium smegmatis, first described by Gray and Ballou (Gray, G. R., and Ballou, C. E. (1971) J. Biol. Chem. 246, 6835-6842) is now shown to be a mixture of at least four isomers separable by gel filtration owing to differences in size and degree of methylation. The major component is 3-O-methylmannose but all contain small amounts of mannose. The molecular weights range from 2040 to 2490 and all are nonreducing. After Smith degradation, all yield a single large and one or more small fragments that give 3-O-methylmannose as the sole product of complete acid hydrolysis. The large Smith-degraded MMP components (SD-MMP) are similar to intact MMP and vary from 1830 to 2130 daltons, consistent with the loss of a single mannose; whereas the smaller fragments are the size of tri- to hexasaccharides and result from fragmentation of incompletely methylated chains. Controlled acid hydrolysis of [methyl-3H]MMP releases 6% of the methyl groups as [3H]methanol at a rate characteristic for the hydrolysis of methyl alpha-D-mannopyranoside. Proton magnetic resonance spectra of MMP and SD-MMP show a major methyl ether proton peak and a second small peak at higher field equivalent to about one methyl group per molecule. The results are consistent with the presence of an alpha-methyl aglycon at the reducing end of the chains. Methylation analysis of MMP isomers purified by high pressure liquid chromatography confirms that they are linear and unbranched. Methylation of [methyl-3H]MMP yields unlabeled tetra-O-methylmannose, showing that the chains are terminated by mannose. However, digestion of [methyl-3H]MMP with alpha-mannosidase releases mannose and exposes [methyl-3H]3-O-methylmannose. Smith degradation of [methyl-3H]MMP III yields a penta-to hexasaccharide product that can be resolved by high pressure liquid chromatography into two components. The distribution of radioactivity between these two fragments suggests that the chain was cleaved near the middle and that there must be an unmethylated mannose at that position. We conclude that the 3-O-methylmannose polysaccharides are linear unbranched chains of 11 to 14 sugar units, each terminated by a single mannose at the nonreducing end and by a methyl aglycon at the reducing end. Each isomer shows microheterogeneity, with 1 or 2 unmethylated mannose units near the middle of some but not all of the chains.


An alternating site sequence for oxidative phosphorylation suggested by measurement of substrate binding patterns and exchange reaction inhibitions. Catalysis by beef heart submitochondrial particles of the medium Pi in equilibrium HOH, Pi in equilibrium ATP, and the ATP in equilibrium HOH exchanges is strongly inhibited while the ATPase and intermediate Pi in equilibrium HOH exchange are accelerated when medium ADP is removed by pyruvate kinase action. Arsenate readily blocks completely the Pi in equilibrium ATP and medium Pi in equilibrium HOH exchange reactions, but not the ATP in equilibrium HOH exchange reaction. The residual ATP in equilibrium HOH exchange in presence of arsenate is inhibited by 2,4-dinitrophenol. These results and other data are explained by an alternating site model for oxidative phosphorylation. In this model during net oxidative  phosphorylation ATP is formed at one site but is transitorily tightly bound and not released until ADP and Pi bind at a second site and the membrane ATPase complex is energized. Under conditions of net ATP hydrolysis, ATP binding at one site is accompanied by hydrolysis of the transitorily tightly bound ATP as a second site. Attractive features are only one site of input for conformational energization of the membrane ATPase, a single conformational transition that accounts for both the promotion of ADP and Pi binding in a competent mode and the release of tightly bound ATP, and a symmetry of catalytic sites. The Pi in equilibrium ATP exchange is not inhibited by increase in MgADP and MgATP at constant ratios, and the energy-linked ADP in equilibrium ATP exchange is not inhibited by increased concentrations of MgATP and Pi at a constant ratio. Such exchange patterns indicate a random binding and release of ADP and Pi.


Binding of 25-hydroxycholecalciferol in tissues. Evidence is presented that the 5.8 S 25-hydroxycholecalciferol-binding protein found in the cytosols of all nucleated rat tissues is formed from two macromolecular substances: a heat-stable 4.1 S 25-hydroxycholecalciferol-binding protein which behaves identically with the serum 25-hydroxycholecalciferol-binding protein, and a cytosolic heat-labile protein which appears to sediment around 4 S and does not show binding properties for 25-hydroxycholecalciferol. The 5.8 S complex is formed in vitro by incubating cytosols with appropriate amounts of serum. The complex is dissociated by heating, leaving the serum 25-hydroxycholecalciferol-binding protein. Complex formation also occurred with serum 25-hydroxycholecalciferol-binding proteins from other species. The widespread occurrence of the 4 S cytosolic component raises the possibility that the high affinity binding proteins for 25-hydroxycholecalciferol observed in nucleated tissues are largely the result of plasma contamination.


Chemical synthesis of phosphorylated retinoids. Their mannosyl acceptor activity in rat liver membranes. Phosphorylated retinoids were synthesized by a modification of the procedure that Popják et al. (Popják, G., Cornforth, J. W., Cornforth, R. H., Ryhage, R., and Goodman, D. S. (1962) J. Biol. Chem. 237, 56-61) used to synthesize farnesylpyrophosphate. The all-trans-beta-retinyl phosphate; all-trans-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraene-1-yl phosphate; perhydromonoeneretinyl phosphate; all-trans-beta-retinoyl phosphate; 13-cis-beta-retinoyl phosphate derivatives were tested as acceptors of [14C]mannose from GDP-[14C]mannose in a reaction catalyzed by rat liver membranes. The phosphate esters all functioned as acceptors of mannose to give a product chromatographically indistinguishable from endogenous mannosylretinyl phosphate. The mixed anhydrides, however, did not function as mannosyl acceptors. Neither class of compounds had any effect on the biosynthesis of dolichylmannosyl phosphate. Rat liver membranes did not catalyze the transfer of [14C]galactose from UDP-[14C]galactose to retinyl phosphate even at a concentration of retinyl phosphate (0.73 mM) which stimulated formation o mannosylretinyl phosphate by more than 50-fold...


Solanum glaucophyllum as source of 1,25-dihydroxyvitamin D3. Vitamin D-deficient rats given an aqueous extract of the South American plant Solanum glaucophyllum accumulate 1,25-dihydroxyvitamin D3 in their blood and intestines at the time they show enhanced intestinal calcium absorption. The identity of the 1,25-dihydroxyvitamin D3 was established by co-chromatography with 1,25-dihydroxy[23,24-3H]vitamin D3 on Sephadex LH-20 columns, microparticulate silica gel columns, a reversed-phase column developed under high pressure, and by a specific 1,25-dihydroxyvitamin D3 binding assay. The chromatographic systems used are fully capable of resolving all of the known metabolites of vitamin D3. Serum of the S. glaucophyllum-treated rats showed 300 pg/ml of 1,25-dihydroxyvitamin D3 and no detectable 1,25-dihydroxyvitamin D2. Similarly, intestine of such rats had 230 pg/g of 1,25-dihydroxyvitamin D3. Control animals which received the vehicle instead of S. glaucophyllum had only 20 pg/ml of 1,25-dihydroxyvitamin D3 in their serum and 4.4 pg/g of 1,25-dihydroxyvitamin D2 in their intestine. These results demonstrate that S. glaucophyllum extracts must be a source of 1,25-dihydroxyvitamin D3; thus a significant basis for the calcinogenic properties of S. glaucophyllum must be the presence of a conjugated form of 1,25-dihydroxyvitamin D3, which is rendered available by digestion.