Experimental bacterial keratitis in neutropenic guinea pigs: polymorphonuclear leukocytes in corneal host defense. Quantitative techniques were used to determine the relative concentrations of viable bacteria and polymorphonuclear leukocytes (PMNs) in the corneas of neutropenic and non-neutropenic guinea pigs with experimental bacterial keratitis induced with three strains of Pseudomonas aeruginosa. Neutropenia was produced by whole-body X-irradiation 1 week before infection. Significantly greater numbers of bacteria were present in the cornea of neutropenic animals 48 h after infection than were present in the corneas of non-neutropenic animals. The same was true 24 and 48 h after infecting animals with Staphylococcus aureus. Examination of histological sections showed that fewer PMNs were present in the corneas of infected neutropenic animals than in the corneas of infected non-neutropenic animals. Radiolabeling of PMNs confirmed a significant reduction in PMN concentration in the corneas of infected neutropenic animals. Tears and the corneal epithelium appear to be the most important elements protecting the cornea against local invasion by bacteria. However, once bacterial keratitis is established, PMNs play a role in limiting bacterial multiplication.


In vivo conjugal transfer of R plasmids in Neisseria gonorrhoeae. In vivo R plasmid transfer between two Neisseria gonorrhoeae strains was detected in the absence of antibiotic pressure.


Nephelometric activity as a criterion of adequate antisera for use in immunofluorescence. We have characterized monospecific sheep antisera to human IgG, IgA and IgM using Ouchterlony double diffusion, immunoelectrophoresis, quantitative precipitation and nephelometric activity. The antisera were conjugated at high and low F/P ratios, absorbed and subsequently evaluated in both direct and indirect immunofluorescence. Antisera which exhibited excellent reactivity in double diffusion, IEP and quantitative precipitation but gave a poor nephelometric response (Ab dilution greater than 1/25 gave no measurable response in the Technicon Fluoronephelometer) showed a marked decreased effectiveness in both direct and indirect fluorescence. Antisera which exhibited a strong nephelometric response were invariably excellent in double diffusion, IEP and quantitative precipitation and gave strong positive fluorescence at reasonable dilutions in both direct and indirect fluorescence. We suggest nephelometry prior to conjugation is the method of choice in screening antisera usable in immunofluorescence.


Large agarose beads for extracorporeal detoxification systems. Preparation and enzymatic properties of agarose-bound UDP-glucuronyltransferase. UDP-glucuronlytransferase, E.C. 2.4.1.17, has been solubilised from the microsomal fraction of liver homogenate from phenobarbital pretreated rabbits by lipase or detergent treatments. A 110-fold purification of the enzyme with respect to the crude homogenate was achieved by precipitation and column separations. The cholate-detergent solubilised enzyme was far more stable than that prepared by the lipase method. The partially purified UDP-glucuronyltransferase has been covalently bound to cyanogen bromide-activated agarose in the form of large haemocompatible beads to the extent of 0.22 mg protein per mg agarose dryweight, equivalent to about 25 mg of swollen gel. The acceptors for glucuronidation employed were the non-physiological phenolic compounds p-nitrophenol and 1-naphthol, and an exogenous and endogenous substance of physiological importance, namely paracetamol and phenol respectively. The immobilised enzyme exhibited at least 80% of the original activity of the solubilised enzyme, and the catalytic function was preserved for a much longer period of time in the carrier-bound form. The system described in this publication could well be applied in an extracorporeal liver assist device for the replacement of glucuronidation function.


Diflunisal, a new analgesic, in the treatment of postoperative pain following removal of impacted mandibular third molars. Diflunisal, 5-(2', 4'-difluorophenyl) -salicylic acid, has been shown in animal and human studies to possess pronounced analgesic and anti-inflammatory effects. The objective of the present investigation wa to compare the analgesic effect and safety of three doses of 500 mg diflunisal, given orally over 36 h, with placebo in the treatment of pain following surgical removal of impacted mandibular third molars. A total of 60 patients, 30 patients in each treatment group, participated in this double-blind, completely randomized study. The treatment groups were compared for demographic data, disease-related variables and pretreatment severity of pain. According to both the investigator's and the patient's overall evaluation of treatment efficacy on postoperative pain, diflunisal was significantly better than placebo (P less than 0.0001). Clinical adverse reactions were reported by seven patients (25%) in the diflunisal group compared to three patients (11%) in the control group. In two instances the adverse reactions were rated by the investigator to have been "unacceptable". The overall conclusion of this study is that diflunisal, compared to placebo, is a highly effective and well-tolerated analgesic in the treatment of postoperative pain following surgical removal of impacted mandibular third molars.


Facial asymmetries following unilateral condylar replacement. An experimental study in monkeys using metatarsal transplants. The aim of the present study was to evaluate qualitatively and quantitatively the effect of metatarsal transplantation on the mandibular condylar region. Two series of experiments were performed in four groups of Rhesus monkeys, a fifth group served as a nonoperated control group. The surgical procedures involved either the condyle and part of the ramus or the condyle only. Following the postoperative observation period the skulls of the animals were examined macroscopically, measured anthropologically and measured indirectly on vertical cephalograms. A new method developed by the authors for description of facial asymmetries was used. In all of the operated animals well-functioning joint structures were revealed, though all experimental groups showed the classical deformation features. Continued growth of the transplant was observed in only one case. The facial asymmetries were described as angular deviations from the true symmetry axis. No significant difference between the transplant and the corresponding nontransplant groups was detected for the two kinds of resection performed. However a difference in the degree of asymmetry between the ramus resection group and the condylectomy group was seen. It is concluded that a metatarsal transplant does not prevent the development of facial asymmetry following plain condylectomy or resection of the posterior third of the ramus of the mandible including the condyle.


Unilateral enlargement of the masseter muscle. Benign hypertrophy of the masseter muscle is a relatively uncommon condition which may occur unilaterally or bilaterally. The etiology of the ailment is unclear in the majority of cases, and the histopathological features are usually those of normal muscle. A case of unilateral masseter muscle enlargement is described in a 19-year-old Arab male. The histopathological findings were compatible with a mild myopathic disorder. The characteristics, differential diagnosis, etiology, treatment and histopathological features of masserteric hypertrophy are discussed.


Penetration of disposable needles.

Penetration of disposable needles. Six types of disposable injection needles were tested clinically for the intensity of pain caused, and their penetration capacity measured. The force nedded differed greatly with different needle types (120-250 mN). The design of the needle point was observed to have the greatest effect on the pentration capacity and the intensity of pain. To penetrate the tissue well, the needle point should have secondary bevels at the tip of the bevelled surface. The majority of the needles fulfilled this requirement.


Herpes zoster of the maxillary branch of the trigeminus nerve. Virological and serological studies. A 70-year-old male had erythematous and vesiculous lesions in the area of the right maxillary branch of the trigeminus nerve and was clinically diagnosed as having herpes zoster; virological and serological investigations of this case were carried out. Consequently, an electron microscopic observation revealed a great number of virus particles of herpes type in the vesiculous lesion and in baby hamster kidney BHK21/WI-21 cells, cultured after inoculating the fluid from the vesicle formed on the patient's upper lip or from serum harvested during the viremia. When BHK21/WI-21 cells infected with this virus were tested for antigenicity by an indirect immunofluorescent staining technique, they showed a positive staining to antivaricella-zoster virus. When serum of this patient was assayed fof the antibody level against varicella-zoster virus by the complement fixation test at various time intervals during the therapeutic period, this antibody titer on recovery period showed a threefold increase in comparison to that at onset. From these findings, this infectious disease was precisely diagnosed as herpes zoster.


Lingual sulcoplasty with a modified preparation technique. Different techniques to improve the denture supporting area in the mandible by means of lingual sulcoplastry are discussed. A method for lingual sulcoplastry is presented and compared with other methods. This method is considered superior to transplantation and flap techniques as it causes less pain and discomfort and allows an early finish of the denture work. Yet the result of the operations with this technique seems to be compatible.


Sagittal split technique I. Immediate postoperative conditions. A radiographic follow-up study. The postoperative appearance of 28 patients was studied following sagittal split osteotomy. A radiological evaluation of the direction and location of the split, secondary unwanted fractures and the area of overlap and contact relationship between the fragments was carried out. In 70% of the cases examined the line of cleavage broke through on the medial surface of the ramus. Unwanted fractures occurred in five of the 56 operated rami, however, these did not influence the postoperative healing to a great extent. The area of overlap between the fragments varied from 3-10 cm2. In some cases diastases of up to 8 mm were noted. The true area of contact as such was significantly less than the area of overlap.


Sagittal split technique. II. Radiographic findings during the fixation period. A radiographic follow-up study. The radiological appearance of 28 patients following sagittal split osteotomy was studied during the fixation period. Larger areas of overlap and smaller diastasis between the fragments were more frequently associated with short periods of fixation (7 weeks or less). This difference was not statistically significant. In 84% of the operated sides varying degrees of decalcification could be seen within the bone structures. Using tomographic images callus formation between fragments could be registered in 75% of the cases before or at the termination of the fixation; these cases were all stable after removal of fixation. With the exception of two cases the remaining 25% were clinically stable, however, although callus formation could not be demonstrated radiographically.


Sagittal split technique. III. Postoperative rest conditions. A radiographic follow-up study. The radiological appearance of 26 patients was studied 11--53 months postoperatively following sagittal split osteotomy. In 75% of the cases examined an increase in the mandibular angle could be noted compared to pretreatment values. This differences was statistically significant. In 70% of the cases the angle increased by 1--10 degrees. In 25% there was no change or reduction in the angle. The antero-posterior width of the rami was found to decrease; when this was combined with an increase in the mandibular angle, extensive morphological changes were found. These postoperative conditions must be regarded as unsatisfactory and a modification of the technique of sagittal split osteotomy should be considered as for example advocated by EPKER4.


Cryosurgery in stomato-oncology. A report of experiences gained over three years. An account is given of the application and results of cryosurgery in stomato-oncology based on experiences gained over a 3-year period. Altogether 277 patients were treated for oral neoplasia and hemangiomas. It is stressed that cryosurgery is especially applicable for treating benign and malignant lesions of the anterior third of the oral cavity where healing is good, complications few, and inspection fairly easy. To date the short observation periods offers no adequate basis for making a direct comparison of this method with other more conventional techniques in complex tumor therapy.


Diagnosis of an obstructed calyceal diverticulum by ultrasonography. A case is reported in which diagnosis of a calyceal diverticulum, at the time of observation of cystic appearance, was made by ultrasonography, without requiring special roentgen diagnostic procedures of limited safety.


Local application of THIO-TEPA in the prevention of recurrent papillary carcinoma of the bladder. Prophylactic total THIO-TEPA treatment was employed in 44 cases over a period of five years, following radical surgery (including reoperations) for recurrent vesical papillomatosis or carcinoma, and numerous subsequent transurethral coagulations or resections owing to multiple recurrences. Three patients have been now free from recurrences for five years, 13 patients for four years, 11 patients for three years and 9 patients for two years. Eight patients proved unresponsive, the recurrence rate having remained unaffected. No toxic effects requiring any special measures were encountered.


Chronic pyelonephritis. Electron microscopic study. III. The ureter. The ultrastructure of the ureter in the nonhuman primate is described. In experimentally produced chronic pyelonephritis, the ureter shows extensive ultrastructural changes throughout the wall. The epithelium has cellular damage progressing from the basal cells to the superficial cells. There is an invasion of leukocytes into the intercellular spaces at all levels. The connective tissue layer seems thickened with an increase in active fibroblasts, leukocytes, collagen, and elastic fibers. There are various stages of damage in the smooth muscle layer and an abnormal increase of connective tissues between bundles and smooth muscle cells. The interdigitating nexuses seem stretched and altered. The changes are similar to those seen in ureteral obstruction and are assumed to be reparative.


Normalized thyroxine as a screening test for hypothyroidism in full-term and preterm newborn babies. Thyroid function was assessed in full-term and preterm newborn babies by serum thyroxine (T4), normalized thyroxine (T4N) and thyroid-stimulating hormone (TSH) assays. At age 24 h, there was a significant difference in T4 and TSH values between the full-term and preterm groups; no such difference was found in the T4N values. By 21 days of age, the TSH values were still significantly higher in full-term babies compared with preterm ones, but the T4 values were similar. The T4, T4N and TSH values at 24 h in preterm newborns with respiratory distress syndrome were similar to those in normal preterm babies, and the changes in these values with age had no consistent pattern. In preterm babies with low 24-h T4 and T4N values, these two parameters increased with age, reaching normal adult values by 21 days. We concluded that T4N could serve as a useful thyroid function test in the newborn.


Restoration of CSF [HCO3-] after its experimental lowering in normocapnic conditions. It is accepted that in hypercapnia the rise in cerebrospinal fluid bicarbonate concentration (CSF [HCO3-]) occurs because of local HCO3--generating mechanisms, dependent on carbonic anhydrase, as well as on diffusion of HCO3- from plasma. To investigate further the regulation of CSF [HCO3-], CSF HCO3- formation was studied under conditions of pure isocapnic CSF "metabolic" acidosis. In anesthetized normocapnic dogs CSF [HCO3-] was lowered to approximately 15 mmol/l by perfusing the brain ventricles with a low HCO3- solution for 45 min. In dogs with normal plasma [HCO3-], CSF [HCO3-] rose by approximately 7 mmol/l in 2 h after the end of the perfusion. Lowering plasma [HCO3-] to 10 mmol/l by infusing HCl, limited the CSF [HCO3-] rise to 2 mmol/l, indicating the importance of plasma HCO3- for the restoration of CSF [HCO3-]. The small and persistent rise of CSF [HCO3-] at low plasma [HCO3-] occurred against a concentration gradient with blood. Intraventricular injection of acetazolamide had no further effect on this small rise. It is concluded that under the conditions of our experiments the CSF [HCO3-] rise is significantly dependent on plasma [HCO3-] and the caronic anhydrase-dependent HCO3- generation in the CNS is less important.


Effect of betamethasone on pressure-volume relationship of fetal rhesus monkey lung. We have investigated the acceleration of fetal lung maturity following glucocorticoid administration. Air-filling of saline-filling pressure-volume curves were obtained on fetal rhesus monkey lungs after treatment with betamethasone. With air filling there was a marked increase in the total lung capacity (ml air/g at 40 cmH2O) in the treated animals. By normalizing the curves and plotting volume as a percent maximal volume, we examined the shape of deflation curves, a common functional measure of surfactant activity. We found little difference in the shapes between control and steroid-treated animals. With saline filling there was also a similar increase in the lung capacity. As surface tension has a negligible effect on saline pressure-volume curves, we conclude that the primary functional effect of glucocorticoids on the fetal lung may not be an alteration of surface forces. Rather the glucocorticoids seem to accelerate maturity more by increasing lung compliance through structural changes that allow the lung to contain more air for equivalent transpulmonary pressures or pressure changes. This may occur either by increasing the distensibility of already inflatable alveoli or by recruiting new units.


Isolation of mutants deregulated in phosphate control of candicidin biosynthesis. Mutants have been isolated in which phosphate does not inhibit the biosynthesis of candicidin. At high phosphate concentrations, candicidin production by phosphate-deregulated mutants is still inhibited, but to a lesser extent than in the wild type. Some of these mutants are higher candicidin producers than the wild type, not only in phosphate-supplemented medium but also in non-supplemented production medium. The high candicidin production by these mutants is due to (1) a high specific rate of candicidin biosynthesis and (2) an extended production phase. None of the phosphate-deregulated mutants in which uptake of [32P]phosphate was measured was a phosphate-permeability mutant.


Aggregation of sponge cells. Function of a lectin in its homologous biological system. For the first time, the biological role of a lectin in the process of reaggregation of single cells from the same species (marine sponge: Geodia cydonium Jam.) is described. The galactose-specific lectin does not promote aggregation, but prevents the antiaggregation receptor from disaggregating cell clumps. Competition experiments showed that the lectin inactivates the antiaggregation receptor by binding to it, most likely via its terminal galactose residues. The lectin converts reversibly aggregation-deficient cells (carrying functional cell membrane-bound antiaggregation receptor molecules) to aggregation-susceptible cells.


Purification and properties of Bacillus subtilis inositol dehydrogenase. Inositol 2-dehydrogenase (EC 1.1.1.18) activity appears during growth of Bacillus subtilis (strain 60015) in nutrient sporulation medium. Its synthesis is induced by myo-inositol and repressed by D-glucose. The enzyme has an apparent molecular weight of 155,000 to 160,000 as determined by sucrose density gradient centrifugation, and it is comprised of four subunits, each having a molecular weight of 39,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The isoelectric point of the enzyme is 4.4 as determined by column isoelectric focusing. The enzyme shows the highest Vmax and lowest Km with myo-inositol as substrate but does not react with scyllo-inositol; it also reacts with the alpha anomer (but not the beta anomer) of D-glucose and with D-xylose. Apparently, the enzyme can remove only the single equatorial hydrogen of the cyclitol or pyranose ring. In contrast to the glucose dehydrogenase of spores, which reacts with D-glucose or 2-deoxy-D-glucose and with NAD or NADP, inositol dehydrogenase requires NAD and does not react with 2-deoxy-D-glucose.


Purification and properties of phosphorylated isocitrate dehydrogenase of Escherichia coli. Phosphorylated NADP+-isocitrate dehydrogenase (EC 1.1.1.42) has been purified to electrophoretic homogeneity from in vivo 32P-labeled Escherichia coli. The cells used as the source of phosphorylated enzyme were harvested 1 h after the addition of 5 mCi of [32P]orthophosphoric acid and 25 mM sodium acetate to cultures grown to early stationary phase on a low phosphate medium with limiting glucose. Double immunodiffusion and autoradiography demonstrated immunological identity between the 32P-labeled NADP+-isocitrate dehydrogenase and the enzyme isolated from glucose-grown E. coli. The phosphoenzyme had an apparent subunit molecular weight of 51,000 as determined by denaturing acrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, and the radioactivity co-electrophoresed with NADP+-isocitrate dehydrogenase activity when purified enzyme was subjected to nondenaturing gel electrophoresis. [32P]Phosphoserine was identified following partial acid hydrolysis of the purified phosphoenzyme.


Ribosomal protein alterations in thiostrepton- and Micrococcin-resistant mutants of Bacillus subtilis. Ribosomal proteins of parental thiostrepton- and micrococcin-sensitive Bacillus subtilis cysA14 and thiostrepton-and micrococcin-resistant mutants were compared. Several electrophoretic and immunochemical techniques showed unambiguously that BS-L11 was not present on 50 S ribosomal subunits from the six thiostrepton-resistant mutants. Protein BS-L11 reappeared in all six revertants from thiostrepton resistance to thiostrepton sensitivity. No definitive protein alteration could be ascribed to the mutation from micrococcin sensitivity to resistance. It was also demonstrated that B. subtilis protein BS-L11 is homologous to Escherichia coli ribosomal protein L11. The finding that ribosomes from thiostrepton-resistant mutants do not contain protein L11 suggests that L11 not only is involved in binding of thiostrepton, but also, when mutationally altered, confers resistance to this antibiotic. Although the ribosomes of these strains do not contain protein L11, all thiostrepton-resistant mutants showed the same viability as the parental strain. Thus protein L11 cannot be obligatory for the structure and function of the ribosome.


Effect of endo-beta-galactosidase on intact human erythrocytes. Endo-beta-galactosidase, a glycosidase that hydrolyzes Gal beta 1-4 GlcNAc linkages in glycoconjugates, has been used to probe the plasma membrane of human erythrocytes. Coomassie blue staining of stroma components separated by sodium dodecyl sulfate-acrylamide gel electrophoresis indicates that treatment of red cells with endo-beta-galactosidase converts Protein 3, the anion transporter of the erythrocyte, to a more compact staining band. No other components detected by Coomassie staining are affected. Following labeling of red cells with galactose oxidase + NaB3H4, 45 to 50% of the [3H]galactose residues can be released by endo-beta-galactosidase. In contrast, only 5% of the label incorporated by treatment with periodate + NaB3H4, can be removed. [3H]Galactose residues are released from three components: Protein 3, Band 4.5, and the megaloglycolipids. The susceptibility of these components to endo-beta-galactosidase, together with the high content of Gal and GlcNAc present in Protein 3 and the megaloglycolipids, suggests that the erythrocyte membrane contains several components with N-acetyllactosamine repeating units, a structure commonly found in connective tissue glycoconjugates.


Purification and partial characterization of rat liver bilirubin glucuronoside glucuronosyltransferase. Bilirubin glucuronoside glucuronosyltransferase (EC 2.4.1.95) converts bilirubin monoglucuronide to bilirubin diglucuronide and is concentrated in plasma membrane-enriched fractions of rat liver homogenates. The enzyme was purified 2,000-fold to homogeneity from rat liver. The pI of the enzyme is 7.9 +/- 0.2. The enzyme has a molecular weight of 160,000 and is an oligomer of 28,000 dalton subunits. Km for purified enzyme was 35 microM and Vmax was 2.2 mumol of bilirubin diglucuronide formed/min/mg of protein. Freshly biosynthesized bilirubin monoglucuronide was injected intravenously into homozygous Gunn rats which had bile duct cannulation. Gunn rats lack UDP-glucuronate glucuronyltransferase activity (EC 2.4.1.17), have normal bilirubin glucuronoside glucuronosyltransferase activity, cannot form bilirubin monoglucuronide in vitro or in vivo, and do not excrete bilirubin glucuronides after intravenous injection of unconjugated bilirubin. Within 1 h, approximately 75% of the injected conjugated bilirubin was recovered in bile, of which 20% consisted of bilirubin diglucuronide. These results indicate that bilirubin glucuronide glucuronosyltransferase catalyzes conversion of bilirubin monoglucuronide to diglucuronide in vivo.


DNA-directed in vitro synthesis of beta-galactosidase. Purification and characterization of stimulatory factors in an ascites extract. Previous studies have described a partially defined system for the DNA-directed in vitro synthesis of beta-galactosidase (Kung, H.F., Redfield, B., Treadwell, B.V., Eskin, B., Spears, C., and Weissbach, H. (1977) J. Biol. Chem. 252, 6889-6894). An Ehrlich ascites extract was shown in these in vitro studies to acylate Escherichia coli tRNA with 13 amino acids, and the ascites extract was used in place of the corresponding 13 E. coli aminoacyl-tRNA synthetases. The present studies indicate that the ascites extract is supplying an additional protein factor, besides the aminoacyl-tRNA synthetases, that stimulates the DNA-directed synthesis of beta-galactosidase. The protein factor has been highly purified and may be functioning by protecting mRNA against degradation. In addition, NAD or T4 DNA ligase stimulates the synthesis of beta-galactosidase in the partially defined system.


Membrane-bound and soluble extracellular alpha-amylase from Bacillus subtilis. Extracellular alpha-amylase was purified to homogeneity from a Marburg strain of Bacillus subtilis. The enzyme is a single polypeptide chain of molecular weight approximately 67,000. Its NH2-terminal amino acid sequence is Leu-Thr-Ala-Pro-Ser-Ile-Lys. A membrane-derived alpha-amylase was solubilizing from membrane vesicles by treatment with Triton X-100 and was highly purified by chromatography on an anti-alpha-amylase-protein A-Sepharose column. Membrane-derived alpha-amylase was indistinguishable from the soluble extracellular enzyme by sodium dodecyl sulfate-gel electrophoresis and radioimmunoassay. The membrane-derived enzyme contains phospholipid. Approximately 30 to 80% of the phospholipid was extracted from the purified enzyme by chloroform:methanol. The extracted phospholipid was predominately phosphatidylethanolamine. Treatment with phospholipase D released phosphatidic acid. Membrane-bound alpha-amylase was latent in membrane vesicles. Release of membrane-bound alpha-amylase from vesicles by an endogenous enzyme was maximal at pH 8.5, was inhibited by metal chelators and diisopropyl fluorophosphate and was stimulated by Ca2+ and Mg2+. The amount of membrane-bound alpha-amylase was related to the level of secretion.


[Heavy chain disease: humoral and cellular findings in six patients with mu chain disease (author's transl)]. Clinical and chemical findings in 6 patients with mu-chain disease are reported. In all of these patients a lymphoproliferative disease was observed which by its symptoms resembled CLL. This similarity was underlined by the finding of an impaired response of PBL of the patients to mitogens as PHA, PWM, and Con A. A substantial result of our studies lies in the fact that the presence of mu-chains in the serum does not correlate with a clinically defined entity. Moreover, mu-chains have been observed in a case of benign lymphadenopathy. In one case a good remission of 4 years duration could be induced by the application of cytostatic agents.


Degradation of proteins microinjected into cultured mammalian cells. Iodinated proteins were degraded after injection into HeLa cells at first-order rates with half-lives varying from three hours for the trout monhistone chromosomal protein, HMG-T, -to 60 hours for whale myoglobin. Fluoresceinated-bovine serum albumin (fl-BSA) was degraded almost twice as fast as unmodified BSA. The rate of degradation of 125I-BSA was very similar in eight cell lines of mouse, human, monkey and rat origin. Microinjected proteins were analyzed on SDS-acrylamide gels after injection, and for BSA and immunoglobin G, all remaining intracellular 125I migrated at the molecular weight of the injected proteins. By contrasting, more than 80% of the extracellular 125I chromatographed as iodotyrosine. With the exception of fl-BSA, which exhibited perinuclear accumulation in approximately one-half of the injected cells, autoradiography showed that throughout the period of study the injected proteins remained dispersed in the cytoplasm.


Lymphocytes with immunoglobulin E Fc receptors in patients with atopic disorders. Lymphocytes from normal nonallergic donors and patients with atopic disorders were analyzed for subpopulations bearing Fc receptors for immunoglobulin (Ig)E (Fc(epsilon)) and IgG (Fc(gamma)), surface IgM (sIgM) and IgD (sIgD), and for T cells forming spontaneous rosettes with sheep erythrocytes (E). The patients were divided into three groups according to serum IgE concentrations and systemic corticosteroid treatment. Group I consisted of 12 atopic patients with either normal or moderately increased IgE levels up to 4,000 U/ml. Four patients of group II and three of group III had 10,500-31,000 U/ml and severe atopic dermatitis. Patients of group III, but not I and II, were receiving corticosteroids systemically. The percentage (mean +/-SD) and total number of Fc(epsilon) (+) lymphocytes were 1.2+/-0.5%, 41+/-24/mm(3) in 12 normals; 1.6+/-0.9%, 59+/-43/mm(3) in patients of group I: 7.0+/-2.0%, 187+/-67/mm(3) in group II; and 0.3+/-0.1%, 13+/-5/mm(3) in patients of group III. The increase in group II and decrease in group III of Fc(epsilon) (+) cells were statistically significantly different from the normal persons and patients of group I. In contrast, the patients did not differ significantly from the donors in sIgM(+), sIgD(+), Fc(gamma) (+), and E(+) cell populations. As shown by depletion of sIg(+) cells in four patients with atopic disorders, the great majority of the Fc(epsilon) (+) lymphocytes were B cells. However, two patients with elevated Fc(epsilon) (+) cell numbers had small numbers of mixed E- and Fc(epsilon)-rosetting cells, presumably T cells. Two patients of group II were examined during an acute herpes simplex infection. Both showed an congruent with80% decrease of Fc(epsilon) (+) cells at that time. No apparent correlation between numbers of Fc(epsilon) (+) cells and IgE level existed in patients of group I. Injection of an IgE myeloma protein into two monkeys did not significantly change their percentages of Fc(epsilon) (+) lymphocytes. The data indicate that Fc(epsilon) (+) lymphocytes are increased in patients with markedly elevated serum IgE and severe atopic disease, suggesting that these cells may be involved in the regulation and(or) synthesis of IgE antibody formation.


Differential diagnosis of hypoechoic and anechoic masses with gray scale sonography: new observations. With the technological advances in gray scale sonography that have permitted the use of higher-frequency transducers and expansion of the acoustic dynamic range, increasing problems in differentiating solid masses and fluid-filled masses have become apparent. These difficulties can be overcome by strict adherence to proper scanning techniques, which involve transducer selection, tissue attenuation compensation, and alterations in patient position. The availability of variable-dynamic-range signal processing and the use of real-time scanning can further increase one's confidence in the correct interpretation of these masses. The primary criteria for determining that a mass is fluid-filled have been expanded to include the presence of reverberation echoes, the "lateral shades" sign, and the presence of septations. In the past, hypoechoic masses with low-level internal echoes were termed "complex". Both fluid-filled masses and solid masses may fall into this category. By use of the sonographic criteria, an attempt should be made to determine whether a mass is primarily fluid-filled or solid. Specific anatomic locations and pathologic conditions in which differential diagnosis may be difficult are illustrated; these include abdominal masses, hepatic and renal masses, and pelvic masses.


In vitro investigation of gallstone shadowing with ultrasound tomography. A phantom was constructed to simulate the in vivo situation of gallstone detection. Gallstone specimens from 37 patients were scanned. All gallstones cast acoustic shadows, regardles of the specific properties of the stones. Experimental evidence concerning factors that affect the detection of acoustic shadows from gallstones is discussed.


Ultrasonic real-time guidance for percutaneous puncture. Real-time scanning was applied to the sonically guided puncture technique. A special puncture attachment connected to the ultrasound sector scanner was developed for this purpose. A puncture needle is introduced into the scanning plane through the canal in the attachment. Excellent real-time images of both the target lesion and the needle can be clearly seen on the oscilloscope during the puncture procedure. Puncture not only for cystic structures but also for solid masses can be made easily and safely by this new technique. Successful applications of the technique have been carried out for renal cyst puncture, percutaneous antegrade pyelography, percutaneous nephrostomy, percutaneous renal biopsy, and perineal prostatic biopsy.


Echogenic fluid: a pitfall in the ultrasonographic diagnosis of cystic lesions. Although it is well known that biliary sludge can produce fine diffuse echoes within the gallbladder, it is less commonly appreciated that other cystic structures may contain echogenic fluid and therefore be mistaken sonographically for solid lesions. In this article three cases of splenic cysts and one case each of pyrometrocolpos, hydroureter, and pyonephrosis presented with diffuse fine echoes in the fluid. Three of these cases were misinterpreted as a result of this echogenic appearance. These cases serve to emphasize the need for awareness of the echogenicity of some types of fluid and the value of other signs of cystic lesions besides absence of internal echoes.


Ultrasound evaluation of American Burkitt's lymphoma. Burkitt's lymphoma is a childhood disease that characteristically produces large, bulky abdominal tumors. Although these are potentially curable, chemotherapy can produce rapid tumor lysis, with subsequent life-threatening metabolic abnormalities, especially in those patients with large tumors or those who have compromised renal function. Twenty-two patients with proven Burkitt's lymphoma were evaluated by ultrasound. Thirteen patients had abdominal masses. These masses tended to be large, solitary, and acoustically homogeneous. Although most of these tumors were found in the pelvis, upper abdominal and retroperitoneal tumors were also encountered. None of the patients had the typical paravertebral mantle of enlarged nodes seen in other types of lymphoma. In 11 patients with abnormal intravenous pyelograms, ultrasound successfully distinguished between renal lymphoma, hydronephrosis, and, by exclusion, metabolic renal disease. The absence of lymph node disease and the presence of bulky homogeneous extranodal tumor are characteristic ultrasound findings in Burkitt's lymphoma. By locating and quantifying tumor mass and distinguishing between renal lymphoma and hydronephrosis, ultrasound proved to be clinically useful in the management of this disease.


Ultrasound characteristics of abdominal abscesses involving foreign bodies (gauze). Three cases of abdominal abscesses involving gauze were studied by B-mode ultrasound. Thick irregular boundary echoes and irregular internal echoes of high amplitude were most characteristic. The ultrasound tomograms are presented, and their characteristics are discussed.


Cancer therapy with ultrasound: a historical review. The 45-year history of research in cancer therapy involving ultrasound may be divided into the four periods of initiation, enthusiasm, pessimism and revival. There have been three approaches to the subject: studies have sought to measure the effects on tumors of a) ultrasound alone; b) ultrasound in combination with radiotherapy, and c) ultrasound in combination with chemotherapy. With the first approach the results have varied. In some cases, decreased growth rates or regressions of tumors have been reported; in other cases, either no effect has been observed or growth has been increased. With the second approach, for some tumors, combined treatment has produced greater effects on tumors than has x-ray alone, whereas in other tumors the addition of ultrasound has produced no change. With the third approach, enhancement of the effects of drugs has been observed in melanoma and mouse tumor cells treated with ultrasound and several anticancer drugs. The mechanism of action in most (but not all) cases has appeared to be absorption heating. The potential of ultrasound to provide local tumor control and to enhance other therapy modes has motivated the current efforts by several groups to further study and understand it actions on malignancies.


A monoclonal macroglobulin with antinuclear activity. Serum containing a monoclonal IgM protein from a patient with Waldenstroms' macroglobulinaemia gave intense immunofluorescent staining of kidney nuclei. The Fab mu fragments of this immunoglobulin were obtained. The IgM and Fab fragments reacted in vitro with kidney nuclei using unfixed cryostat sections of rat or mouse kidney. After treatment of the patient with chemotherapy, the monoclonal IgM disappeared, and no more antinuclear activity could be detected in the serum. The results strongly suggest that this IgM protein had antinuclear activity.


Intravenous feeding in a gastroenterological unit: a prospective study of infective complications. We have assessed the bacteriological safety of a system of intravenous feeding by culturing catheters on removal, swabs taken from the catheter's skin entry sites, and samples of infusion fluid. Among 38 treatment periods using 51 catheters over 1551 patient days, septicaemia due to Staphylococcus aureus was observed in one treatment period and bacteraemias due to Staphylococcus albus and Diphtheroid species in two others. The Staph. aureus and the diphtheroids probably gained access via the skin entry site along the outside of the catheter. The origin of the Staph. albus was uncertain. Parenteral nutrition over extended periods can be a safe procedure if aseptic precautions are taken. The importance of the catheter's skin entry site as a source of contaiminating organisms is emphasised.


Prospective economic evaluation of lead poisoning prevention programs. This paper illustrates an economic methodology for the prospective evaluation of individual lead poisoning screening and prevention programs. A method is presented for prospectively estimating the prevalence and expected health consequences of lead poisoning in an urban population. The economic costs of these consequences are calculated and cost-benefit analysis is used to complete the evaluation. A case study is developed to illustrate the potential utility of the model as a framework for the prospective evaluation of programs under funding consideration.


A pathological basis for the cutaneous papules of mucopolysaccharidosis II (the Hunter syndrome). Cutaneous papules of two patients with the Hunter snydrome (mucopolysaccharidosis II) were compared with their normal appearing skin by light and electron microscopic techniques. While most fibrocytes of normal and papular skin contained metachromatic cytoplasmic material and characteristic vacuoles, only the papules had extracellular accumulation of metachromatic material and evidence of coalescence and rupture of vacuoles. Alcohol fixation provides better preservation of the mucosubstances.


Post-secretory aggregation of caseins.

Post-secretory aggregation of caseins. Particles as large as several micrometer diam. have been observed occasionally in normal milk and commonly in prepartum and postpartum colostrum. These particles can be dissociated by EDTA and their appearance closely resembles that of normal casein micelles. However, they are often too large to have been completely formed within the Golgi vesicles of mammary epithelium and hence some degree of post-secretory aggregation of caseins is thought to occur. Two possible mechanisms of post-secretory aggregation of caseins are: (1) a continuation of the normal processes of micelle assembly in the alveolus and (2) aggregation as a result of limited proteolysis of the caseins during the time the milk is in the mammary gland. Incubation of milk with fibrinolysin, however, failed to produce aggregation of normal micelles.


Implementation of a personalized clothing policy for long stay psychiatric patients: a study of communication. This study raises the following question. Should the policy maker be responsible for ensuring adequate monitoring of policy implementation? A policy lays down a course of action for achieving a particular end. Implementation of a policy implies adherence to the course of action stated in the policy. This study was concerned with the relationship between a policy of personalized clothing and the implementation of a particular scheme. Divergence from the original policy occurred because of inadequate communication between those who formulated the policy, those who implemented the policy and the staff who were responsible for day-to-day management associated with the policy. The finding of this study was that the way policy was implemented did not relate to the original objective of the policy. Policy relating to a particular area of health cannot progress scientifically unless evaluation of the implementation of formulated policy occurs. This research therefore advocates that the policy maker should be responsible for ensuring adequate monitoring of the policy when it is implemented.


Permeability of the hard tissue bridge formed after pulpotomy with calcium hydroxide: a histologic study. Analysis of these results shows that complete hard tissue bridges, aside from occurring with great frequency, produce a satisfactory protection to the pulp. In a case in which the barrier is incomplete, some future clinical problems may result as an incomplete barrier does not offer adequate protection as shown by the chronic inflammatory reaction in the remaining pulp tissue.


Relationship between airway hyperreactivity and hyperpermeability in Ascaris-sensitive monkeys. In four Ascaris-sensitive rhesus monkeys, we measured the fractional absorption of 3H-histamine (3HH) and airway response, as pulmonary resistance (R1), to standard histamine aerosols containing tracer amounts of 3HH for control runs (Run 1) and runs after Ascaris antigen challenge (Run 2). The mean rate of accumulation of radioactivity in the plasma volume as a function of delivered dose during histamine exposure (2 min) was fivefold greater for Run 2 (0.047% delivered dose/min) as compared with Run 1 (0.009% delivered dose/min). Whereas histamine inhalation led to insignificant (less than 25%) increases in R1 over control in Run 1. R1 increased by 247% over control after histamine inhalation in Run 2. Thus, both airway hyperpermeability and hyperreactivity to inhaled histamine were observed following specific antigen challenge in this animal model. These data are consistent with the hypothesis that airway mucosal hyperpermeability induced by an allergic reaction is one of the factors contributing to airway hyperreactivity by increasing flows of inhaled bronchoactive agents to effector sites in the airway wall.


Spin-off cost/benefits of expanded nutritional care. Eight years ago, in caring for persons with diabetes at Grady Memorial Hospital, Atlanta, priority was given to the use of oral hypoglycemic agents and insulin, with only minimal attention to nutrition. In 1971, an "expanded nutritional care program" was instituted, with emphasis on nutritional education and follow-up. Use of oral agents was discontinued, and, since 1972, less insulin has been used. The new dietary program, with dietitians playing a key role, includes a one-week total fast, stringent low-calorie diets, individualized dietary planning and instruction, and careful follow-up monitoring. Comparative pre-1971 and current data show: a 50 per cent reduction in lower extremity amputations, less diabetic ketoacidosis, fewer hospitalizations, weight reduction of 40 per cent with no increase in plasma glucose (in a 127-patient cohort with complete follow-up), and a savings to the hospital of more than $96,000 in the cost of medications and $3,700,000 in hospitalizations in eight years.


Erythrocyte folate levels in young and old. Erythrocyte folate levels were compared among 25 young healthy subjects (mean age, 27 years), 29 healthy subjects aged over 75 living in the community, 62 subjects (mean age, 75) admitted to a geriatric assessment ward (acute illnesses), and 32 subjects (aged over 65) in a ward for long-term physical or mental illnesses. Overall, the female/male sex ratio varied from 2:1 to 3:1. For the three elderly groups, the incidence of low erythrocyte folate levels (less than 100 mmicrogram/100 ml) were 24 percent, 16 percent, and 18 percent, respectively. For the young group, the mean value would be over 296 mmicrogram/100 ml. Dietary folate deficiency may often account for low folate blood levels in the elderly, but other factors should also be implicated, e.g., the ability to absorb folate.


Improving the quality of life for the elderly. The United States Senator from Maryland, as speaker at the Awards luncheon of the American Geriatrics Society (Washington meeting), presented his views on priorities in various health programs for the elderly, and asked for the Society's cooperation in making some of the difficult decisions that lie ahead. An important item is cost-effectiveness. These decisions will affect every discipline involved in geriatrics, and have an important bearing upon the quality of life for the elderly. A better understanding is needed of the interaction between aging and disease, and the use of preventive measures.


Thinning of capillary walls and declining numbers of endothelial mitochondria in the cerebral cortex of the aging primate, Macaca nemestrina. Samples were obtained from the frontal and occipital cortex of Macaque monkeys at 4, 10 and 20 years of age. Electron microscopic studies revealed attenuation of capillary walls and declining numbers of endothelial mitochondria per capillary profile with increasing age. The basal lamina surrounding the capillary increased in thickness between 4 and 10 years of age; however, it did not undergo further change between 10 and 20 years. These results corroborate morphological and biochemical studies indicative of declining numbers of mitochondria, and decreasing mitochondrial ATP synthesis and ATPase activity in other tissues during aging.


Histochemical detection of carbonic anhydrase with diemthylaminonaphthalene-5-sulfonamide. A new specific method for the detection of carbonic anhydrase, EC 4.2.1.1, in tissues is described. The reaction of carbonic anhydrase with dimethylaminonaphthalene-5-sulfonamide (DNSA) forms a highly fluorescent complex. The specificity of the method is proved by the quenching of this fluorescence with ethoxzolamide (6-ethoxybenzothiazole-5-sulfonamide). The difference in the wavelength makes it possible to absorb the fluorescence of the unbound dimethylaminonaphthalene-5-sulfonamide by filters. Kidney, proventriculus, and bone from chicken have been examined. Carbonic anhydrase has been detected in the cytoplasm of the columnar lining cells, proximal tubule cells, and osteoclasts.


Very low frequency and small intensity electromagnetic and magnetic fields as an oecological factor. The effect on microorganisms of electromagnetic and magnetic fields (EMF, MF), the frequency and intensity of which were similar to natural ones, was studied. They were found to influence the physiology of bacteria. Changes in the rate of proliferation of microbes, in their susceptibility to antibiotic the frequency of formation of recombinants and partial diploids during conjugation of colibacterium were observed during cultivation in these fields.


[Epidemiologic and serologic study of listeriosis in man and domestic and wild animals in Austria]. In the framework of a study aimed to ascertain the possibilities of infection transmission from mother to child the athors examined serologically gravid women for toxoplasmosis and antibodies against listeriosis, using routine methods, in Austria in 1974, 1975 and 1975. Almost all gynecologists of the region of Styria (Austrial), who systematically delivered data concerning abortions, premature births and stillbirths, were invited to take part in the study. At the same time data concerning domestic and wild animals examined for antibodies against listeriosis in Austria in 1974, 1975, 1976 and 1977, were compared.


Nutritional support in patients with malignant disease. Clinicians have long been aware of the major nutritional and metabolic abnormalities that occur in patients with cancer. Such abnormalities are varied and hence both the indications and techniques for their correction are also diverse. The aim of the present paper is to consider certain specific aspects of nutritional support in cancer and the authors end with a brief review of areas of study which may prove useful in future.


Genetics of Drosophila subobscura populations. VIII. Allozyme loci and their chromosome maps. Genetic information on 25 enzyme polymorphisms in Drosophila subobscura, the location of corresponding genes, and cytological and genetic maps of the chromosomes are presented, as well as photographic maps of the salivary gland chromosomes in the third instar larva and white-case early pupal stages. Biochemical markers were used to establish chromosomal homologies among D. subobscura, D. pseudoobscura, D. melanogaster, and D. willistoni.


Parenteral nutrition in the cancer patient. The nutritional state of patients with malignant disease must be assessed at the beginning of treatment. Nutritional supplements, given either orally or intravenously, enable patients to tolerate larger doses of chemotherapy and radiotherapy and the clinical response may be enhanced by nutritional support. Crystalline L aminoacids and glucose are the main nutrients used intravenously and fat emulsions are required in prolonged parenteral nutrition. Hypophosphataemia related to glucose administration and infection related to access to the circulation are the main complications, both of which are preventable. Total parenteral nutrition alone will not improve the results of cancer treatment significantly but its careful use in association with surgery, radiation therapy and chemotherapy can be most valuable.


Hyperthermia and radiation-induced dominant lethals and chromosome loss in female Drosophila melanogaster. The hyperthermia treatment, 38 degrees C for 1 hour significantly increased the dominant lethals induced by 1000R of X-rays in immature oocytes. The viability and chromosome loss in mature eggs were affected by either heat treatment or radiation. Hyperthermia treatment given before radiation exposure also significantly increased radiation-induced loss of the X chromosome in immature oocytes. Heat treatment did not increase radiation-induced nondisjunction of the chromosomes.


The carboxy-terminal peptides of in vitro precursor and in vivo mature kappa light chains are identical. Protein structural analysis of several precursor light chains indicates that these in vitro products include a cysteine-containing tryptic peptide that is indistinguishable from the carboxy-terminal tryptic tripeptide present in in vivo mature kappa light chains. It is concluded that although in vitro precursor light chains contain an additional amino-terminal sequence, their carboxy-terminus is the same as that found in in vivo mature light chains.


An immunologic approach for the detection of tumor cells in the peripheral blood of patients with malignant lymphoma; implications for the diagnosis of minimal disease. Lymphocytes were isolated from infiltrated lymph nodes and blood of eight patients with malignant lymphocytic lymphoma. All patients had normal numbers of circulating lymphocytes with normal morphology. None of the patients had serum paraproteins. The isolated lymphocytes from patients and controls were stained with affinity purified antibody specific for kappa- or lambda-light chains and analyzed by using a fluorescence activated cell sorter. Cells from infiltrated nodes stained for only one light chain type at high levels of fluorescence intensity. An increase in the number of brightly stained cells bearing the light chain type found in the involved node was readily detected in the peripheral blood of all but one of the patients with lymphoma. Similar changes in the ratio of kappa+- to lambda+-cells were not observed in 41 samples from nomral individuals and patients with other diseases.


Murine cell surface immunoglobulin: two forms of delta-heavy chain. The heavy chain of isolated murine cell surface IgD is present in two forms, separable by electrophoresis on SDS-polyacrylamide gradient gels. Both forms of delta-heavy chain are present on the surface of intact spleen cells and have apparent m.w. of approximately 70,000 (delta1) and 68,000 (delta2). Treatment of surface IgD with neuraminidase before isolation results in a single IgD heavy chain band on SDS gels having an apparent m.w. of 65,000, indicating that delta 1 and delta 2 differ in sialic acid content. Delta 2 is removed from the cell surface by papain more readily than delta 1, suggesting a possible functional significance for the two forms.


Ir gene defects may reflect a regulatory imbalance. I. Helper T cell activity revealed in a strain whose lack of response is controlled by suppression. A singular responsiveness to HEL was revealed in a peripheral lymphoid compartment of the genetically nonresponsive H-2b mouse. Although i.p. injection of HEL induces suppression and a lack of anti-HEL production, following footpad injection there is an early emergence in the popliteal lymph node (P-LN) of HEL-specific helper activity and plaque-forming cells. Furthermore, the early P-LN transiently expresses one of two T cell types needed for initiation of suppression. Delayed recruitment of the second required cell-type permits the induction of efficient suppression. There is only a short period during which there is concurrent representation of the two T cell subpopulations, and by mixing early and late deficient P-LN T cells, suppression could be established. The general implication of these results is that although a vigorous helper cell potential may exist in a strain nonresponsive to a multideterminant antigen, it can be obscured by a regulatory cell imbalance that results in the manifestation of a generalized Ir gene "defect."


Immunoquantitation of antibody to placental phosphatase by single radial immunodiffusion; effect of antibody avidity and immunization protocol. The radial immunodiffusion method was used to titer antisera to human placental alkaline phosphatase. When this was done with diluted enzyme and antisera, it was found that early-course antisera consistently yielded low titers. This observation was consistent with the known low avidity of such antisera.


Is the d an allelic gene of D in the Rh blood group system? A quantitative study using 99mTechnetium-pyrophosphate-labelled antibody (TcLA) method. This article reports on studies of Rh antigens, such as D, Du and d, using uranyl-labelled antibody (ULA) and TcLA (99mTc-pyrophosphate-labelled antibody) methods for the first time for this purpose. TcLA method proved to be simple in labelling and very sensitive (20--100 times more so than the indirect Coombs test) in the detection of Rh antigen-antibody binding. Results of this quantitative study demonstrate convincingly that the d is not an allelic gene of D but rather the weakest of the series D less than Du less than d. Although the evidence from this study demonstrates clearly that differences between D and d are only quantitative, the authors do not think that the Rh nomenclature should be changed but they do think that the present evidence should be used in regard to the understanding of the allelism in the Rh blood group system. The c is an allelic gene of C as the e is an allelic gene of E; specific test sera detecting every one of these antigens exist and the family studies verify these statements. However, the d is not a distinct antigen as c and e are, even if the pattern of inheritance from family studies, using the existent anti-D serum, would suggest the allelism as probability. That is why in the past the anti-Du and anti-d specific test sera never incidentally found or artificially produced.


Familial incidence of precipitating antibodies in von Willebrand's disease: a study of four cases. Precipitating antibodies directed toward human F.VIII/WF were found in the plasma of four out of 17 multitransfused patients with severe, homozygous-like VWD. The familial incidence was illustrated by the development of these antibodies in three patients from the same kindred. Such antibodies, titrated with newly developed quantitative assays of anti-VIIIR:Ag and anti-VIIIR:RCo, were directed toward only these components of F.VIII/WF. VIII:C was neutralized in a time-independent manner in plasma and was not inactivated when separated from F.VIII/WF by solid-phase PE absorption. Plasma, serum, or immunoglobulin reacted in precipitation systems (immunodiffusion, EID, CIE) with human VIIIR:Ag, with some degree of cross-reactivity toward VIIIR:Ag from other mammalian plasmas. When used in IRMA, these antibodies demonstrated the same abnormalities as heterologous antisera in variant VWD: decreased binding affinity or nonparallelism of the dose-response curves. They are polyclonal IgG with both kappa and lambda light chains. It is suggested that in some patients with severe homozygous-like VWD, the synthesis of the component of F.VIII/WF carrying VIIIR:Ag and VIIIR:RCo is suppressed whereas VIII:C production is not completely abolished.


Model of the bacterial flagellar motor: response to varying viscous load. A model of bacterial flagellar drive by cytomembrane streaming is described and applied to experiments of bacterial propulsion under varying viscous load. The theory predicts a linear dependence of the reciprocal propulsion velocity on the viscosity of the suspension medium, if the velocity of cytomembrane streaming far from the basal body of the flagella is assumed independent of the external viscosity. The theoretical predictions are in good agreement with experiments on free-swimming and on tethered bacteria. From comparison of the theory with experiments, the surface viscosity of the bacterial cytomembrane is evaluated for different bacterial species and turns out to be in the range observed experimentally on lipid monolayers.


Purification of the cytoplasmic oestrogen receptor from mammary tumours induced in rats with dimethylbenzanthracene. The oestrogen receptor from mammary tumours induced in rats by dimethylbenz(a)-anthracene has been extensively purified by affinity chromatography and isoelectric focusing. The unpurified cytoplasmic 8 S oestrogen receptor had a molecular weight of 240,000, a Stokes radius of 5.4 nm and a frictional ratio of 1.32; the Km (dissociation constant) at 4 degrees C for [3H]oestradiol-17 beta was 0.184 nmol/l. At the end of affinity chromatography the molecular weight was still 240,000 but under the conditions of isoelectric focusing it was reduced to 110,000, with a Stokes radius of 4.0 nm, a frictional ratio of 1.26 and an isoelectric point of 6.4.


Intra-uterine tissues from late-pregnant rhesus monkeys (Macaca mulatta) produce 6-oxo-prostaglandin F1 alpha in vitro. The rates of production of 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha) in vitro by intra-uterine tissues taken from late-pregnant monkeys at Caesarean section have been determined. For tissues obtained between days 140 and 149 of pregnancy (late pregnancy) the general quantitative order of rates of production (per unit weight) was decidua basalis greater than placenta greater than decidua parietalis greater than amnion greater than chorion = myometrium. When tissues were taken between days 160 and 168 of pregnancy (near term) this order was placenta greater than decidua parietalis = amnion greater than myometrium = decidua basalis greater than chorion. There was a significant reduction near term in the rate of production of 6-oxo-PGF1 alpha by decidua basalis; all other tissues exhibited similar rates of production at the two gestational periods investigated.


Prostaglandin E, thromboxane B2 and 6-oxo-prostaglandin F1 alpha in amniotic fluid and maternal plasma of rhesus monkeys (Macaca mulatta) during the latter third of gestation. The concentrations of prostaglandin E (PGE), thromboxane B2 (TXB2) and 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha) were measured by radioimmunoassay in serial samples of amniotic fluid and maternal peripheral plasma in the latter third of pregnancy in rhesus monkeys (Macaca mulatta). The samples were collected under ketamine-induced anaesthesia. The concentration of PGE was undetectable in amniotic fluid until a few days before delivery when a large increase was observed in three of the five animals. There were small increases of TXB2 and 6-oxo-PGF1 alpha in amniotic fluid before delivery. In maternal plasma the concentrations of PGE, TXB2 and 6-oxo-PGF1 alpha were generally higher and more variable than in amniotic fluid and did not increase with advancing gestation. It is suggested that increased production of primary prostaglandins occurs before, and is involved in, the onset of parturition in the rhesus monkey.


Effect of thyrotropin releasing factor on body weight of the pond snail Lymnaea stagnalis. Earlier studies had demonstrated that in Lymnaea stagnalis thyrotropin releasing factor (TRF) may be the secretory product of the so-called dark green neurosecretory cells. The dark green cells are believed to serve an osmoregulatory function. If TRF is the secretory product of the dark green cells, it should be capable of controlling the salt and water balance in L. stagnalis. In this study, the effect and fate of synthetic TRF injected in vivo into L. stagnalis was assessed. It was found that TRF caused an increase in the rate of loss of body water which normally occurs after anaesthesia. TRF also increased the loss of body water when it was administered to unanaesthetized animals. The peptide was accumulated and degraded by the tissues of the foot, mantle, and head regions, tissues which are believed to be the targets of the hormone of the dark green cells. Our results support the hypothesis that TRF may be the secretory product of the dark green cells and may be involved in osmoregulation in L. stagnalis.


Dopamine-dependent hyperactivity in the rat following manipulation of GABA mechanisms in the region of the nucleus accumbens. The effect of manipulation of GABA mechanisms in the region of the nucleus accumbens on dopamine-dependent locomotor hyperactivity in the rat has been studied. Two models of hyperactivity were used: (1) the injection of dopamine into the region of the nucleus accumbens in nialamide-pretreated animals and (2) the systemic administration of d-amphetamine. Both GABA and the GABA agonist 3-aminopropane sulphonic acid (3-APS) depressed hyperactivity in a dose-related manner. High concentrations of GABA (greater than 100 micrograms) were required to produce a significant effect and the response was short-lived possibly reflecting the efficient GABA inactivating mechanisms. 3-APS proved to be approximately 10 times more potent as compared to GABA in the dopamine-accumbens hyperactivity model. Conversely GABA receptor antagonism with low doses of either picrotoxin or bicuculline enhanced the mild locomotor response induced by a low dose of dopamine injected into the nucleus accumbens. However such results were difficult to evaluate fairly as higher doses of the GABA antagonists resulted in varying degrees of generalized seizures. Blockade of GABA uptake systems with cis-1, 3-aminocyclohexane carboxylic acid (ACHC), nipecotic acid or beta-alanine within the region of the nucleus accumbens produced dose-related depression of dopamine-dependent hyperactivity in both models. GABA uptake blockade (nipecotic acid) significantly enhanced the GABA-mediated depression of hyperactivity induced by bilateral injection of dopamine into the nucleus accumbens. The results demonstrate an inhibitory action of GABA and drugs facilitating GABA-ergic transmission on dopamine-dependent hyperactivity in the rat. Although open to criticisms of not being able to distinguish between true GABA effects and the results of non-specific neuronal depression the hyperactivity model underlines the potency of the GABA uptake blocking compounds and their possible potential for future clinical use.


Kinetics of interaction of ligands with carboxypeptidase A. Rate constants for the interaction of a number of ligands with the active site zinc ion of carboxypeptidase A have been measured at pH 7.0, 25 degrees, 1.0 M NaCl. Polydentate ligands such as EDTA, NTA or CyDta do not accelerate the rate at which the zinc ion dissociates from the protein. Bidentate or tridentate ligands on the other hand are able to attack the zinc ion directly; the rates are first order in enzyme and first order in ligand. A mechanism for the reaction is proposed, in which a ternary complex LZnCPA is formed which rapidly dissociates into ZnL and apo CPA. Comparison of results for a variety of ligands leads to the conclusion that in the ternary complex tridentate ligands bind to the zinc ion through only two donor groups. The reaction of 1.10-phenanthroline with ZnCPA has been studied from pH 6 to 9, and a mechanism proposed which accounts for the pH profile of the reaction.


Identification of dorsal root synaptic terminals on monkey ventral horn cells by electron microscopic autoradiography. The projection of dorsal root fibres to the motor nucleus of the macaque monkey spinal cord has been examined utilizing light and electron microscopic autoradiography. Light microscopy demonstrates a very sparse labelling of primary afferent fibres in the ventral horn. Silver grains overlying radioactive sources are frequently clustered into small groups, often adjacent to dendritic profiles. Under the electron microscope, myelinated axons and a few large synaptic profiles containing rounded synaptic vesicles were overlain by numerous silver grains. These labelled profiles made synaptic contact with dendrites 1-3 micron in diameter. The labelled profiles did not contact cell bodies or large proximal dendrites of ventral horn neurons. Frequently, small synaptic profiles containing flattened vesicles were presynaptic to the large labelled terminals and it is suggested that these axoaxonal synapses may mediate presynaptic inhibition of the primary afferent fibres. The relationship of the present findings to previously published physiological and anatomical studies is discussed.


A cohort study on mortality among dynamite workers. Exposure to nitroglycerine and nitroglycol in the explosives industry is suspected of having caused isolated cases of sudden death. There have also been suggestions of an increased risk of chronic cardio-cerebrovascular diseases among dynamite workers. This study examines the mortality experience of a cohort of male workers from a small Swedish dynamite industry. Cause-, sex-, age-, and calendar-year-specific national incidence rates were used to calculate the expected number of deaths in a group of individuals with exposure to the dynamite manufacturing process and in an unexposed group from the same industry. During the period 1965-77, nine deaths from cardiocerebrovascular diseases were observed, versus 4.5 expected (p less than 0.05), among men with at least one year of exposure to dynamite and 20 years of induction-latency time. The unexposed group had a mortality pattern in good agreement with the national average. Exposure occurred by inhalation as well as through the skin. Precautions are urged to diminish exposure from both these absorption routes as the findings of the study support earlier reports regarding chronic vascular effects.


The significance of alterations of pulpal respiration. A review of literature. Several methods of assessing pulpal injury due to cavity preparation and cytotoxic properties of restorative materials have been developed by previous investigators. Seldom in the literature are the mechanisms of these injuries considered beyond the histological level. This article examines pulpal injury on an ultrastructural and biochemical basis.


Basal cell extensions in human oral mucosa. Basal cell extensions have frequently been observed in a variety of odontogenic lesions as well as in the fibrous epulis (fibrous hyperplasia of the gingiva). In order to determine the frequency of these extensions in normal human oral nucosa, a study using autopsy and surgical material was conducted. The results indicated that a specific type of rete ridge morphology exists for gingiva, including the presence of thin double stranded extensions which may be related to the functional role of the gingiva or to the fact that the odontogenic apparatus is derived from surface epithelium in this region in the developing embryo, or both. Similar extensions have not been found in other oral epithelia.


Immunologic manipulation of DMBA tumorigenesis in hamster cheek pouch by DNCB contact hypersensitivity. Hamster cheek pouches were sensitized with the potent allergen DNCB either before the initiation of DMBA tumorigenesis or by direct application to already developed tumors. Among animals treated prior to tumorigenesis induction there was an apparent delay in onset of tumors and decreased rate of tumor growth. Direct application of DNCB to already established tumors seemed to temporarily arrest tumor growth; later, however, tumor growth rate resumed to approximately that in untreated control animals. It is concluded that DNCB contact hypersensitivity may exert some influence on the DMBA tumorigenesis process as manifested by delay in tumor onset or by temporarily retarding growth of established tumors. It appears that DNCB sensitization prior to tumorigenesis is generally more effective than DNCB applied after tumor development.


224 Ra and 226Ra experimentally induced dental changes in rats. Sprague-Dawley rats received intragastrically a single dose of 226Ra or 224Ra once weekly for 21 weeks. During this period the animals of both groups were thus exposed to comparable doses. After 12 weeks, a shortening of the maxillary incisors was observed, and this progressed during the course of the 55-week experiment. Radiologically, a loss of pulpal transparency and an apical irregular opacity in the maxillary incisors were demonstrable. Histologically, dysplastic changes of the maxillary incisors and multiple resorptions at the cemento-enamel junction of the molars were seen. The observed alterations were more pronounced in the 226Ra group than in the 224Ra treated group. The experimentally induced resorptions were comparable to those observed in patients who had incorporated 224Ra or 226Ra. Clinical, radiological, histological, gamma-spectrometrical, and autoradiographical findings, as well as dose-estimations, are described.


Pigment in the lining of nasopalatine duct cysts: report of two cases. In a review of 20 nasopalatine duct cysts, two cases were encountered with a pigmented epithelial lining. In the literature we have found one similar case only. The pigment in our cases was shown to be melanin. The authors suggest that the melanin-containing epithelial cells are derived from Jacobson's organs and, therefore, most likely should be considered olfactory epithelium.


Fluoride distribution in the facial surfaces of human maxillary central incisors. The fluoride distributions in the incisal, middle and cervical regions of the facial surfaces of six maxillary central incisors were determined by three successive acid etch biopsy procedures. The fluoride concentrations were adjusted to standardized depths of 0--10 micron, 10--20 micron and 20--30 micron. In the biopsy areas the enamel fluoride concentrations decreased with increasing depth. In all the teeth the fluoride content was lowest in the incisal region and highest at the cervical third.


Electromyography after lateral pterygoid myotomy in monkeys. Neuromuscular patterns of five female rhesus monkeys (Macaca mulatta) were studied to determine the effect of laternal pterygoid myotomy on the function of selected groups of masticatory muscles. Activity characteristics of the lateral pterygoid muscle were recorded as early as four days postoperatively. By the end of the second postoperative month, bilateral lateral pterygoid muscle activity was demonstrated in all animals. In all cases, it closely resembled preoperative patterns of lateral pterygoid muscle function. The activity was observed regardless of whether an inert barrier was used to prevent reattachment of the muscle. The results of this study indicate that the lateral pterygoid myotomy does not have a long-term effect of inhibiting the function of the lateral pterygoid muscle.


Presurgical infusion of Proplast: primate facial augmentation. Presurgical infusion of Proplast (Vitek, Inc., Houston) with various solutions has been advoccated to enhance rapid ingrowth of tissue and stabilization of the implant. A comparison of Proplast blocks infused with saline solution, autogenous plasma, plasma with antibiotics, and control blocks was done after subperiosteal implantation in the maxillas and mandibles of primates. At specified time intervals from two to 66 weeks, implants were removed and examined for the character and degree of infiltration of tissue as well as for local cellular response to the alloplast. Microscopic examination of the implant showed increasing stabilization of tissue and decreasing local cellular response with increasing time of implantation. Examination of these parameters showed blocks infused with plasma to be least desirable.


The keratinization potential of crevicular epithelium: an experimental study. Free grafts, consisting of nonkeratinized crevicular epithelium and supporting connective tissue, were placed into recipient beds prepared in nonkeratinized alveolar mucosa of the rhesus monkey. Four weeks later these grafts clinically resembled keratinized gingiva and this was confirmed by biopsy and histological examination. Electron microscopy indicated that the connective tissue supporting the crevicular epithelium changed to resemble that supporting keratinized gingiva in the 4-week graft. These findings were interpreted to indicate that crevicular epithelium has the potential to keratinize and that this potential is only realized when the inflammation is resolved in its supporting connective tissue.


Dependence of p-aminohippurate transport on calcium in canine renal cortical slices. 1. Experiments were conducted on renal cortical slices from sixty-one adult mongrel dogs in order to evaluate the relationship between p-aminohippurate (PAH) transport and calcium. Tissues were found to be viable for at least 180 min.2. PAH uptake and the slice/medium (S/M) concentration ratio increased in normal tissues from 3 to 90 min whether data were expressed on a tissue weight or protein content basis. PAH uptake increased with time in calcium-depleted tissues, but all values were lower than normal. At 90 min, PAH S/M in calcium-depleted tissues (4.20 +/- 0.18) was reduced 40% compared to normal tissues (6.90 +/- 0.23).3. Over the time period of 3-90 min incubation, protein concentration ranged from 89.4 to 99.4 mg/g cortex in calcium-depleted tissues. During the same time period in normal tissues, protein concentration ranged from 105 to 117.6 mg/g cortex. No change was observed in medium protein concentration of calcium-depleted tissues.4. Lineweaver-Burke analysis showed similar values for K(m) in normal and calcium-depleted tissues (0.45-0.50 mumole ml.(-1)) although V(max) fell from control values of 0.082 to 0.052 mumole g(-1) min(-1) during calcium depletion.5. After 90 min incubation, addition of EGTA (7, 14 or 21 x 10(-3)M) to media containing calcium was associated with decreased S/M and uptake rates compared to control values from the same animals. The decreases observed were similar to those seen in tissues incubated in calcium-free media.6. Increased cell volume in the presence of calcium was not associated with decreased PAH uptake. Removal of calcium in association with constant cell volume was associated with reduced PAH uptake. Replacement of calcium, but not magnesium, is associated with a return of uptake to normal rates.7. It is concluded that (a) calcium removal causes increased water uptake into cells, (b) calcium removal causes a reduced V(max), (c) calcium is required for maintenance of intracellular PAH, (d) the effect of calcium on PAH is specific and reversible, and (e) the effect of calcium is not mediated by volume changes.


Effects of permeant monovalent cations on end-plate channels. 1. The time constant of decay (tau D) and peak amplitude of miniature end-plate currents (m.e.p.c.s) were recorded in voltage-clamped toad sartorius fibres. The conductance (gamma) and average lifetime (tau N) of end-plate channels activated by ionophoretically applied acetylcholine were calculated from records of current fluctuations and null potentials recorded in the same fibres. tau D was significantly greater than tau N measured at the same end-plate. 2. Substitution for LiCl for NaCl increased tau D and tau N but decreased gamma and the peak amplitude of m.e.p.c.s. In contrast substitution of CsCl for NaCl decreased tau D and tau N but increased gamma and the peak amplitude of m.e.p.c.s. 3. In normal (Na) solution and in solutions in which Na had been replaced with Li, Cs and K, the ratios of average decay time constants of m.e.p.c.s and average channel lifetimes followed the sequence (tau(Li) greater than tau(Na) greater than tau(Cs) greater than tau(K)). 4. Substitution of Li, Cs or K for Na had little effect on the acetylcholine null potential. Average null potentials in Li, Na and Cs solutions were -6.1, -3.2 and 0.1 mV at 20 degrees C, and -7.3, -5.3 and -0.1 mV at 8 degrees C, respectively. The average null potential in K solution measured at 8 degrees C was -2.4 mV. 5. Peak conductance during an m.e.p.c. (Gp) followed the sequence (Gp(K) greater than or equal to Gp(Cs) greater than Gp(Na) greater than Gp(Li)). Single channel conductance followed a similar sequence of gamma(K) greater than or equal to gamma(Cs) greater than gamma(Na) greater than gamma(Li). 6. The voltage sensitivity of the rate of decay of m.e.p.c.s and of average channel lifetime was affected by substituting monovalent cations for Na, being greater in Li solution and less in Cs or K solutions. The total amount of charge moving across a single channel or across channels activated during an m.e.p.c. was largely unchanged in Li, Na, Cs and K solutions. 7. Single channel conductance and peak conductance during an m.e.p.c. varied with membrane potential in normal (Na) solution, decreasing with membrane hyperpolarization. This effect was more marked in Li solution but was less evident in Cs or K solutions.


The membrane current of single rod outer segments. 1. Outer segments of individual rods in the retina of the toad, Bufo marinus, were drawn into a glass pipette to record the membrane current. 2. Light flashes evoked transient outward currents. The peak response amplitude was related to flash intensity by a Michaelis equation with half-saturating intensity about 1 photon mum-2. 3. The saturating response amplitude ranged up to 27 pA and corresponded closely to complete suppression of the steady inward current present in darkness. 4. For a given cell the saturating response amplitude varied linearly with the length of outer segment within the pipette. This is consistent with a uniform density of light-sensitive channels and negligible gradient of membrane potential along the outer segment. 5. Responses to bright flashes never showed the relaxation from an initial peak seen previously in intracellular voltage recordings, suggesting that the conductance change responsible for the relaxation does not occur in the outer segment. 6. Responses to local illumination of only the recorded outer segment were very similar to those obtained with diffuse light at the same intensity, indicating that peripheral rods made little contribution to the responses. 7. The spectral sensitivity of 'red' rods was consistent with a retinal1-based pigment with lambda max = 498 +/- 2 nm. 8. The kinetics of the response were consistent with four stages of delay affecting action of the internal transmitter. Responses were faster at the basal end of the outer segment than at the distal tip. 9. Background light reduced the sensitivity to a superposed dim test flash and shortened the time course of the response, indicating that adapting light modifies the kinetics and gain of the transduction mechanism within the outer segment. 10. Responses to dim lights exhibited pronounced fluctuations which are attributed in the succeeding paper (Baylor, Lamb & Yau, 1979) to the quantal nature of light.


Responses of retinal rods to single photons. 1. A suction electrode was used to record the membrane current of single rod outer segments in pieces of toad retina. During dim illumination the membrane current showed pronounced fluctuations. 2. Amplitude histograms of responses to dim flashes of fixed intensity exhibited two discrete peaks, one at 0 pA and one near 1 pA, suggesting that the response was quantized. By setting a criterion amplitude level, flash responses could be classed as 'failures' (no response) or as 'successes' (at least one quantal event). 3. The variation of fraction of successes with flash intensity was consistent with the hypothesis that each quantal electrical event resulted from a single photoisomerization. 4. The quantal event had a mean amplitude of about 1 pA (5% of the standing dark current) and a standard deviation of 0.2 pA. Dispersion in the event amplitude prevented identification of histogram peaks corresponding to two or more photoisomerizations. 5. Individual quantal responses exhibited a smooth shape very similar to that of the average quantal response. This suggests that a single photoisomerization releases many particles of transmitter and that radial diffusion of internal transmitter is not a major source of delay in the light response. 6. The 'quantum efficiency' with which an absorbed photon generated an electrical event was measured as 0.5 +/- 0.1 (S.E. of mean, n = 4). This is slightly lower than the quantum efficiency of photoisomerization obtained previously for rhodopsin in solution. 7. At wavelengths between 420 and 700 nm the quantal event was invariant in size, although the cell's sensitivity varied over a range of 10(5). 8. The power spectrum of the fluctuations in dim steady light was predicted by assuming that a random series of quantal events occurred independently. 9. In brighter light the fluctuations were faster, and the response to an incremental flash was reduced in size and duration. The power spectrum could be predicted by assuming random superposition of events with the shape of the incremental flash response.


[Electrophysiological study of hypothalamic neurons and gonadotropin regulation in rhesus monkey (author's transl)]. The electrical activity of various hypothalamic areas was recorded in anesthetized (sodium pentobartital) (n = 3) and unanesthetized (n = 3) ovariectomized rhesus monkeys. The plasma gonadotropin levels of the animals during the recording sessions were obtained by a chronic cardiac catheter. 1. Sodium pentobarbital greatly affected the electrical activity of most hypothalamic neurons (84%). The mean spontaneous electrical unit activity of neurons in the unanesthetized animals (n = 30) was 1.5 spike/sec. This value decreased to 0.1 spike/sec in the anesthetized group (n = 30). However, a small number of hypothalamic neurons were insensitive to the anaesthetic. 2. The multiunit electrical activity recorded in the median eminence showed marked periodic increases, about 200 sec before LH was observed to rise in the plasma (10/12). This increased firing lasted about 10 min (Fig. 1A). 3. In a few cases (2/12), however, increased firing was not associated with LH release. Since, in this area, multiunit activity represents the summation of a large number of axon terminals, the release of a hypothalamic hormone other than Gn-RH is put foreward as a possible hypothesis. 4. Of 51 neurons recorded in various hypothalamic areas, 3 showed periodic increases of electrical unit activity which corresponded to a rise in plasma LH levels (Fig. 1 B). These neurons are located in the arcuate area. 5. These results are consistent with the hypothesis of a relation between the electrical activity of some hypothalamic neurons and the periodical LH discharges observed in the ovariectomized rhesus monkey.


Hypothalamic neurones in culture. I. A short review of the literature. This article probably represents the first comprehensive attempt to review the fast growing literature dealing with mammalian hypothalamic neurones in long-term cultures. The bulk of the experimental data on this topic printed before the second half of 1978 deals with endocrine neurones, their development, their bioelectric properties, their biosynthetic capabilities and with mechanisms of hormone secretion. Most initial studies had been concerned with providing evidence that hypothalamic endocrine neurones preserve some of their characteristic properties in culture. The time has come to gain new insights into their functioning with the use of in vitro techniques that allow the composition of the external environment of the cells to the markedly altered.


[Ontogenesis of hypothalamic control of adenohypophyseal secretions in the human foetus (author's transl)]. The endocrine glands of the human foetus are active early in gestation, and various foetal and placental hormonal contributions are essential for growth and sexual differentiation. 1. The anterior pituitary gland has the ability to synthesize, store and secrete hormones early in gestation. The patterns of change in plasma concentrations of hGH (Fig. 1), ACTH, LH and FSH (Fig. 2) during gestation indicate that secretion is at a maximum at mid-gestation, followed by a progressive decrease towards term. The high levels at mid-gestation can be interpreted as due simultaneously to a high secretion rate, low peripheral catabolism and absence of feedback mechanism. In contrast, the secretions of PRL (Fig. 1) and TSH are moderate at mid-gestation and only increase in the last trimester of gestation. 2. Effective control by the central nervous system (CNS) of the pituitary secretions is still immature at mid-gestation. The presence in the foetal hypothalamus of releasing factors such as LRF (Fig. 5) and TRF, and of somatostatin (Fig. 6), a growth hormone release inhibiting factor (GIF), has been established. TRF and GIF, but not LRF, are also present in the cerebral cortex. It has been postulated that, early in life, relatively autonomous and unrestrained secretion of hypothalamic hypophysiotropic releasing factors occurs, and that, later in development, there is a maturation of inhibitory or restraining influences mediated via the CNS (feedback mechanisms) that modulates the secretion of the foetal adenohypophyseal hormones (Fig. 3 and 4). 3. Observations made with anencephalic newborn confirm that a functional hypothalamus is necessary during foetal life for the secretion of each of the hormones of the anterior pituitary gland with the exception of PRL, the secretion of which is normal in anencephaly. Although somatostatin probably participates in the regulation of hGH during foetal life, it appears evident from the anencephaly data that this regulation can only be fully understood by postulating the existence of a growth hormone releasing factor (GRF).


Peripheral plasma levels of progesterone, oestradiol-17 beta, oestrone, testosterone, androstenedione and chorionic gonadotrophin during pregnancy in the marmoset monkey, Callithrix jacchus. Concentrations of LH/CG, androstenedione and testosterone rose in early pregnancy to maximum values at 6--10 weeks. Thereafter LH/CG levels declined and androstenedione and testosterone levels remained at plateau values or declined until term. Progesterone, oestradiol-17 beta and oestrone increased after ovulation and remained high throughout pregnancy. At 12 weeks, when LH/CG levels were falling, progesterone and oestradiol rose well above the luteal-phase levels which were maintained for the first 12 weeks. Progesterone declined in the 2 weeks before birth, while oestradiol and oestrone remained high. Pregnancies of an unknown stage were dated by reference to a graph of uterine diameter, measured by abdominal palpation, in animals at known times after conception. Measurement of progesterone concentrations during the conception cycle gave more accurate dating and showed that the gestation length was 144 days.


Cyclic changes in the circulating and urinary levels of ovarian steroids in the adult female owl monkey (Aotus trivirgatus). Circulating levels of oestrone and progesterone were measured by radioimmunoassays in plasma samles from 5 female owl monkeys on 60 consecutive days. Both steroids exhibited cyclic fluctuations and based on nadir to nadir intervals the ovarian cycle was estimated to be 15.92 +/- 0.26 days. Levels of oestrone and pregnanediol-3 alpha-glucuronide were also measured in daily urine samples. The fluctuations of urinary steroids reflected those observed in plasma. Ketamine sedation had no effect on the length of the cycle. Peak values of plasma progesterone and oestrone were 250.48 +/- 11.37 and 3.59 +/- 0.066 ng/ml respectively. There was no clear hormonal distinction between the follicular and luteal phase of the cycle in these owl monkeys.


Observations on progesterone production and clearance in normal pregnant and fetectomized rhesus monkeys (Macaca mulatta). The metabolic clearance rate (MCR) and production rate (PR) of progesterone were measured in rhesus monkeys both before and during intravenous infusion of progesterone at rates which approximately doubled or tripled the peripheral plasma levels. The monkeys were normally pregnant or fetectomized and were studied during the second half of pregnancy. Raising the peripheral plasma levels did not significantly after the MCR or the PR of progesterone. We conclude that peripheral progesterone levels are not the factor which controls the PR of progesterone in rhesus monkeys.


Choosing priorities.

Choosing priorities. Dr Gray leaves us with a question at the conclusion of his article--how should we choose priorities? He says that the debate so far has been mainly on what we should choose, but perhaps we should consider how to choose even more. Under the various subheadings of Criteria, Principles and Persons Dr Gray sets out the pros and cons of the arguments in the priority debates and tries to offer some more specific guidelines to offset the criticism that the government's priority discussions have been too generalised. Yet this is a difficult task when everyone's priorities are so different.


Protection by monospecific gonococcal antisera of the chicken embryo challenged with Neisseria gonorrhoeae. The protective effects of monospecific gonococcal antisera on 11-day chick embryos challenged with a known lethal dose of gonococci were assessed. The monospecific antisera were prepared by immunisation of rabbits with purified gonococcal antigens, and removal of trace amounts of unwanted antibodies was achieved by absorption with antigen covalently bound to cyanogen bromide-activated Sepharose beads. The antisera were standardised for IgG by solid-phase radioimmunoassay. Antiserum raised against whole outer membrane was protective and antiserum raised against the lipopolysaccharide (LPS) was moderately protective. Outer-membrane antiserum from which the LPS component was removed by absorption was less protective than either of these sera. Investigation of the protective mechanism of anti-LPS antibodies indicated that in addition to any antitoxic effect, these antibodies inhibited the multiplication of gonococci. Antisera raised against individual outer-membrane proteins offered no protection in this test. Out of five antisera tested, antipilus serum gave the strongest protection when piliate gonococci were used as the challenge in this model; antipilus serum did not protect against challenge with non-piliate gonococci.


Transfer of plasmid-mediated antibiotic resistance in strains of Pseudomonas aeruginosa isolated in Auckland. Of 422 clinical strains of Pseudomonas aeruginosa, 23 (5.5%) were resistant to gentamicin; 19 were also resistant to tobramycin and sisomycin, and one was resistant to tobramycin, sisomycin and amikacin. Of the gentamicin-resistant strains, 20 were also resistant to kanamycin. Sixteen strains with a high level of resistance to gentamicin (MIC greater than 160 microgram/ml) transferred all their resistance determinants to recipient strains of P. aeruginosa and four transferred some resistance determinants to P. aeruginosa but none transferred resistance to a recipient strain of E. coli K12. These results show that gentamicin resistance in strains of P. aeruginosa isolated in Auckland is mediated by R plasmids.


Sensitivity of Neisseria gonorrhoeae to partially purified R-type pyocines and a possible approach to epidemiological typing. Strains of Neisseria gonorrhoeae from a variety of sources were examined for sensitivity to 11 partially purified R-type pyocines from Pseudomonas aeruginosa. Selective inhibition of gonococci by pyocines of Kageyama groups R1 and R5 was observed. "Matched isolates", those from consorts or different body sites of individual patients, usually had very similar pyocine-sensitivity patterns and identical sensitivities to five antibiotics tested. This study included local isolates, strains from diverse geographic regions, and strains from disseminated gonococcal infections. It also proposed a relationship between pyocine-receptor sites in the lipopolysaccharide of Ps. aeruginosa and N. gonorrhoeae. Topics needing further evaluation are discussed.


Differentiation of fluorescent pseudomonads by their effect on milk agar. Eighty-six clinical isolates of fluorescent pseudomonads that did not produce pyocyanin on Diagnostic Sensitivity Test Agar or Cetrimide Agar were identified on the basis of their antibiotic sensitivity, production of pigment on King's "A" medium, growth at 42 degrees C, production of lecithinase and hydrolysis of gelatin. The identity of the strains was confirmed in tests with the ammonium salt sugars ethanol, glucose and mannitol. These tests were adequate for distinguishing between the three important fluorescent pseudomonads. The detection of casein hydrolysis on milk agar was assessed as a rapid method of distinguishing P. aeruginosa from the other species of fluorescent pseudomonads but proved unhelpful when compared with, or included in, a small set of tests. Most strains of P. aeruginosa and P. fluorescens hydrolysed casein.


Absence of ocular pathology after repeated exposure of unanesthetized monkeys to 9.3-GHz microwaves. Unfettered monkeys (Macaca mulatta) have been trained to expose the face and eyes to pulsed microwave radiation at a frequency of 9.31 GHz and an average power density of 150 mW/cm2. Performance of an operant response required the monkeys to maintain the head within the field of the radiation source. Twelve monkeys were individually irradiated during 30 to 40 sessions and then were observed for a period of one year. No deleterious effects such as cataracts have been observed.


Mandatory open reduction: its role in displaced ankle fractures. "Satisfactory reduction" is insufficient in discussing ankle fractures; only perfect anatomic reduction will suffice. Fractures extending into joint surfaces carry a higher incidence of disability than those involving the metaphysis and/or diaphysis. The end result is further adversely affected when such fractures occur in weight-bearing joints with resulting disability from persistent pain and stiffness. It is our belief that anatomic reduction of displaced ankle fractures, especially the restoration of fibular length, is almost impossible by closed reduction. Closed reduction may require frequent manipulation and plaster changes as the swelling subsides, and the fragments become displaced. This encourages ankle and subtalar stiffness. For these reasons mandatory open reduction and rigid internal fixation of these fractures are recommended. A review of 300 nonconsecutive cases of open and closed displaced ankle fractures treated by open reduction had an overall infection rate of 1% and an incidence of degenerative arthritis of 3%.