ATP-dependent activation of L cell glucocorticoid receptors to the steroid binding form. The specific glucocorticoid binding capacity in cytosols prepared from L929 mouse fibroblasts (L cells) is inactivated with a half-life of approximately 2 h at 25 degrees C. As previously published, this inactivation can be prevented with 10 mM molybdate and markedly slowed by addition of other phosphatase inhibitors such as glucose 1-phosphate and fluoride. We have now found that ATP (5 to 10 mM) also slows the rate of this inactivation. After extensively inactivating the receptor by preincubating cytosol at 25 degrees C for 4 and preventing further inactivation by addition of molybdate, addition of ATP results in reactivation of the steroid binding capacity. Maximal reactivation of 40 to 70% is achieved with 5 to 10 mM ATP. The activation is temperature-dependent and specific for ATP. ADP, GTP, CTP, and UTP do not cause activation and preliminary results indicate no effect of cyclic nucleotides in this system. If activation is prevented by addition of 10 mM EDTA to the cytosol, addition of 3 to 10 mM magnesium permits ATP-dependent activation of the binding capacity. The level of reactivation can be enhanced by addition of a heat-stable factor prepared from the same L cell supernatant. These results support the proposal that L cell glucocorticoid receptors can be activated to the glucocorticoid binding state by an ATP-dependent phosphorylation mechanism.


Multiple forms of human renin. Purification and characterization. Human renin was purified from a juxtaglomerular cell tumor with a high renin content, 24.2 Goldblatt units/mg of protein. The purification procedure comprised three steps: gel filtration, DEAE-cellulose chromatography, and preparative isoelectric focusing. Five forms of renin amounting to 5.3 mg of enzyme were obtained with isoelectric points of 4.95, 5.10, 5.35, 5.55, and 5.70. They were all glycoproteins. The three major fractions had very similar specific activities, 868, 860, and 809 Goldblatt units/mg of protein. These fractions produced a single band on analytical isoelectric focusing and a single arc on immunoelectrophoresis. On polyacrylamide gel electrophoresis at pH 7.8, each fraction consisted of two renin bands with the same molecular weight, but different net charges. The molecular weight determined by gel filtration and Fergusson plot analysis on polyacrylamide gel was 38,000 to 42,000. The optimum pH determined on N-acetyltetradecapeptide substrate was 6.5, and the Km was 6.8 x 10(-6) M. These parameters were identical with those for standard human kidney renin. Antibodies raised against tumor renin completely inhibited the activity of both tumor and standard renin. Under dissociating conditions (sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel electrophoresis in the presence of 6 M urea), part of the purified enzyme dissociated into two smaller fragments (Mr = 20,000 and 25,000) containing renin activity.


Studies of the high molecular weight penicillin-binding proteins of Bacillus subtilis. Seven or eight penicillin-binding proteins (PBPs) were detected in Bacillus subtilis membranes. By introducing covalent affinity chromatography employing cephalosporins as ligands, milligram amounts of three high molecular weight PBPs (PBP 1 ab, Mr = 120,000; PBP 2b, Mr = 94,000; and PBP 4, Mr = 78,000) were obtained without any contamination of the major PBP 5, the D-alanine carboxypeptidase. Small amounts of pure PBP 2b could be isolated by manipulation of the affinity chromatography conditions. Structural and physical properties of these proteins as well as the generation of one major penicilloyl peptide from each PBP by digestion with pepsin suggest that each PBP is the product of a separate gene. No enzymatic activity could be found in mixtures of these high molecular weight PBPs employing substrates used for the transpeptidase and D-alanine carboxypeptidase assays in particulate membrane fractions.


The effect of pneumatic tourniquets on the ultrastructure of skeletal muscle. Experiments have been carried out on rhesus monkeys to determine the effect of the application of a pneumatic tourniquet on the ultrastructure of the muscles of the lower limb. Tourniquets were applied for periods lasting between one and five hours. The changes in the muscle lying immediately under the cuff of the tourniquet were more marked than those observed in muscle distal to the cuff. Three hours appears to be close to the limit of the time that a muscle can resist the sustained compression of a tourniquet.


Lisuride hydrogen maleate: evidence for a long lasting dopaminergic activity in humans. In 12 acromegalics a single oral dose of 0.2 mg lisuride, an ergoline derivative, significantly reduced plasma PRL but not GH concentrations. Three-tenths milligram of the drug significantly reduced plasma levels of the two hormones. Four-tenths milligram of lisuride did not augment this inhibitory effect. Plasma PRL levels were suppressed in all patients, whereas GH levels were reduced by more than 50% of the base-line values in only seven patients who also responded to the administration of 2.5 mg bromocriptine (CB154). In the patients unresponsive to lisuride, CB154 also failed to change GH levels. The suppressive effect of lisuride started at 60 min (at 150 min for CB154) and plasma GH and PRL levels were still markedly suppressed at 300 min. Plasma GH and PRL concentrations were consistently reduced in two acromegalic patients during 2 weeks of chronic treatment with 0.3 mg lisuride four times a day. In six normal subjects, TRH-induced PRL release was significantly inhibited by pretreatment with 0.3 mg of the drug. The similarity in the effects of lisuride and CB154 suggests that the observed effects of lisuride on GH and PRL are attributable to the known dopaminergic activity of the drug. This conclusion is supported by the data showing that pimozide effectively counteracted the inhibitory action of lisuride on GH and PRL release. We suggest that lisuride may be of value in the medical treatment of acromegaly and hyperprolactinemic states.


Thyrotropin-releasing hormone is not required for thyrotropin secretion in the perinatal rat. To determine the role of thyrotropin-releasing hormone (TRH) in the regulation of thyroid-stimulating hormone (TSH) secretion in the perinatal period, a physiological approach of neutralizing circulating TRH in the fetal and early neonatal rat was employed. TRH-antiserum (TRH-AS) raised in rabbits and administered daily to low iodine-propylthiouracil (LID-PTU)-fed pregnant rats from days 12 to 19 of gestation markedly impaired the rise in serum TSH to LID-PTU when compared with normal rabbit serum-treated controls. In contrast, fetal serum TSH was unaffected by TRH-AS. The binding capacity of TRH-AS in the fetal serum (111 ng/ml) far exceeded circulating TRH in the fetus. Similarly, acute TRH-AS administration to the pregnant rat fed LID-PTU markedly decreased the serum TSH concentration in the mother, but not in the fetus, 60 min after TRH-AS administration. Chronic TRH-AS administration to neonatal rats whose nursing mothers were fed LID-PTU was in-effective in decreasing the elevated serum TSH in the neonate through day 8 of life, whereas a slight but significant decrease in serum TSH was observed on day 10. Chronic daily TRH-AS administration to neonatal rats through day 10 of life had no effect on the later development of the hypothalamic-pituitary-thyroid axis. These findings suggest that TRH does not participate in TSH regulation during the perinatal life in the rat and that thyroid hormones are probably the main regulators of TSH secretion during this period. Placental TRH is not important in regulating TSH secretion in the fetal rat. Furthermore, TRH "deprivation" during neonatal life does not prevent normal later development of the hypothalamic-pituitary-thyroid axis.


Demonstration and characterization of specific binding sites for factor VIII/von Willebrand factor on human platelets. The presence of specific Factor VIII/von Willebrand factor (FVIII/vWF) binding sites on human platelets has been demonstrated by using 125I-FVIII/vWF and washed human platelets. Binding is ristocetin-dependent and increases in proportion to the concentration of ristocetin from 0.2 to 1 mg/ml. Binding of 125I-FVIII/vWF to platelets can be competitively inhibited by unlabeled human or bovine FVIII/vWF, but not by human thrombin, fibrinogen, alpha 2-macroglobulin, equine collagen, or a lectin of Ricinus communis. Scatchard analysis of binding data indicated that the dissociation constant of FVIII/vWF receptors is 0.45--0.5 nM. There are 31,000 binding sites per platelet at 1 mg/ml of ristocetin concentration. The optimal pH range for binding is from 7.0 to 7.5. At a concentration of 2 mM, EGTA inhibits 86% of the binding; however, 20 mM of Ca++, Mg++, or EDTA have little effect. Binding sites for FVIII/vWF were found only on platelets, and no significant binding was detected with human erythrocytes or polymorphonuclear leukocytes.


High resolution real time ultrasound of the carotid bifurcation. We have been using a high resolution real time ultrasound mechanical sector scanner to visualize the carotid bifurcation. Twenty-six patients were studied before carotid arteriography for transient ischemic attacks. One bifurcation was not adequately visualized. Of the remaining 51, plaques were identified correctly in 29; absence of plaques was identified correctly in 15; small plaques were demonstrated by ultrasound in two that did not appear on the arteriogram; and four small plaques and one significant stenosis were not identified by ultrasound.


Ultrasonography of hemorrhagic splenic cysts. Cysts arising from the spleen are much less common than those arising from other organs such as kidney, liver, and ovary (1). Hemorrhagic cysts of the spleen are rare (1), but we have encountered two patients with this entitiy. The ultrasonograms in each patient demonstrated gravity-dependent layering of two fluids of distinctly different echogenicity. The fluids were contained within a spherical mass. Acoustic enhancement was exhibited behind the mass in each case. This suggested the diagnosis of hemorrhagic cyst.


Identification of fetal growth retardation by ultrasonographic estimation of total intrauterine volume. Recent literature has suggested that total intrauterine volume (TIUV) estimation is useful fir distinguishing normal from growth-retarded fetuses. One hundred seventy-nine measurements of TIUV were obtained from the ultrasonograms taken between 21 and 40 weeks of gestation in 140 patients who delivered average birthweight babies. We constructed a mean curve for TIUV with upper and lower 2.5 and 10% tolerance limits and later evaluated the TIUV's of 16 patients with growth-retarded fetuses. Nine of these fetuses had birthweights below the fifth percentile for gestational age, and in each of these pregnancies the TIUV ultimately fell below the lower 2.5% tolerance limit.


Atypical pseudocysts of the pancreas: an ultrasonographic evaluation. Ultrasonograms of most pseudocysts have a typical appearance--sharply defined, smooth wall, ovoid, located in the region of the pancreas. However, in reviewing the sonographic appearance of pseudocysts, other ultrasonographic characteristics may occasionally be encountered. Eleven patients with atypical pseudocysts are presented. The demonstration of multiple septations, multiple echoes within a sonolucent mass, and even failure to enhance posteriorly should not exclude the diagnosis of pancreatic pseudocyst in the proper clinical setting. The value of serial scans is also stressed. In this series, it was possible to suggest the diagnosis of infection, hemorrhage, and rupture of pseudocysts by demonstrating cysts with more typical appearances on prior examinations.


Ultrasonic visualization of Wirsung's duct: dream or reality? Ultrasonic visualization of normal and pathological Wirsung's ducts has become quite common, especially with the newest gray scale units. Ductal images were studied in 17 cases of quiescent chronic pancreatitis. Duct dilatation could be identified in the majority


Gray scale transrectal ultransonography of the prostate. Gray scale transrectal ultrasongraphy provides refined visualization of the texture of the prostate and other intrapelvic organs. Diagnostic accuracy of the transrectal scan has been successfully registered at 91% in benign prostatic hyperplasia, 85% in cancer, 89% in prostatitis, and 88% in total prostatic scans. Furthermore, prostatic calculi were visible in the tomograms of both normal and abnormal prostates at a higher frequency than generally considered. Other applications of ultrasonic control, such as during transurethral resection or cryosurgery of the prostate and staging of bladder tumors, are profitable using the gray scale technique.


The ultrasonic findings in intussusception of the blind loop in a jejunoileal bypass for obesity. A 34 year old woman with bowel bypass surgery and persistent abdominal pain had intussusception of the blind loop, which was visualized on an abdominal ultrasound examination. The ultransonic and radiographic findings are compared and presented. Ultrasound should prove to be an invaluable tool in evaluating abdominal pain in bowel bypass patients.


Lutembacher's syndrome: recognition by echocardiography. The typical echocardiographic features of mitral stenosis in association with an enlarged right ventricle and abnormal septal motion are generally consistent with pulmonary hypertension and functional tricuspid regurgitation. In the absence of clinical and echocardiographic features of pulmonary hypertension, the combination of mitral stenosis and "volume overload" of the right ventricle should alert the clinician to the diagnosis of Lutembacher's syndrome. This report discusses a patient with these echocardiographic findings in whom the diagnosis of Lutembacher's syndrome was confirmed by cardiac catheterization.


Ultrasonographic demonstration of a placental maternal lake. A 30 year old woman was seen at 32 weeks of gestation because of severe abdominal pain. A sonogram revealed an irregular, 5 cm-diameter cystic structure in the placenta. Examination of the placenta after cesarean section showed an extremely large maternal lake.


Evaluation of a quarter wavelength matching layer transducer in abdominal scanning. A focused ultrasonic transducer employing quarter wavelength matching technology is compared to one of conventional design. The effect of the 6 db improvement in signal-to-noise ratio is demonstrated.


Applications of real-time ultrasound in obstetrics: the linear and dynamically focused phased arrays. Real-time ultrasound is a dynamic imaging technique that allows in utero orientation to the fetus. It permits rapid and efficient examination of fetal anatomy and provides a dynamic assessment of fetal well-being. The energy dissipation can be comparable to that in conventional ultrasonic B-mode scanning. We have used both linear and dynamically focused phased arrays for fetal examinations in conjunction with conventional gray scale B-mode scanners. The sophisticated phased-array real-time systems have demonstrated higher resolution and an improved gray scale as compared with the linear arrays. Applications of real-time ultrasound in obstetrics are discussed, and appropriate clinical examples are cited that illustrate the value of the technique for study of both normal and abnormal fetal development. We believe that this technique is the most sensitive method of detecting intrauterine fetal demise. The relative advantages and disadvantages of linear and dynamically focused phased arrays in obstetric evaluation are considered.


Correlation between sectional area of the spleen by ultrasonic tomography and actual volume of the removed spleen. The sectional area of the splenotomogram scanned parallel to the ribs provides useful information for differential diagnosis and determination of prognosis in liver diseases. To establish a relationship between sectional area and actual spleen volume, 10 spleens obtained at splenectomy or autopsy were studied. A good linear correlation (r = 0.956) was present between the sectional area (S) and the actual spleen volume (V). The spleen volume could be calculated as V = 7.5S - 77.5. Therefore the value of the sectional area obtained from one ultrasonic splenotomogram has practical application as a parameter reflecting the spleen volume in vivo.


The normal pancreas: acoustic characteristics and frequency of imaging. This article reports the results of a study designed to evaluate both pancreatic echogenicity and success of visualizing recognizable pancreatic tissue. The acoustic characteristics of the normal pancreas were compared with those of the liver. Of 100 scans reviewed, 65 scans (65 percent) depicted recognizable pancreatic tissue. Two cases were discarded on the basis of hepatocellular disease, and one case was discarded because of hepatic metastases. Thirty-two cases demonstrated pancreatic echogenicity greater than that of the liver, and 30 cases demonstrated pancreatic echogenicity equivalent to that of the liver. We found no normal pancreas that displayed less echogenicity than the liver. A hypothesis is offered to explain the observed results.


Hepatic arteries and the parallel-channel sign. The sonographic parallel-channel sign is not pathognomonic of dilatation of the biliary tree. Often, the so-called parallel channel is a hepatic artery. The differentiation between a bile duct and a hepatic artery is usually possible with good sonographic technique.


Ultrasound evaluation of hydronephrosis of pregnancy. Four hundred ninety-two patients, including 449 pregnant patients, 39 nonpregnant control patients, and 4 patients with pelvic masses, had renal ultrasonography using gray scale technique. Measurements of renal pelvic diameters in the normal pregnant patients revealed an overall incidence of 63 percent renal pelvic dilatation over the nonpregnant controls. Maximum normal renal pelvic diameters were 1.1 cm on the right and 0.9 cm on the left. The maximum normal expected renal pelvic diameter (97.5 percent confidence level) in pregnancy is 2.7 cm on the right and 1.8 cm on the left in the last two trimesters of pregnancy. There was no significant difference between primiparous and multiparous patients, but pregnant patients were significantly different from controls in every trimester (p less than 0.01). Maximum dilatation occurred at 24--28 weeks of gestation. The right renal pelvis was enlarged to the greatest degree in 90 percent of normal patients. Patients with pelvic masses showed a similar pattern of right-sided hydronephrosis.


Intrauterine pseudogestational sac in ectopic pregnancy. Ultrasonic diagnosis of ectopic pregnancy has been thought to depend on exclusion of intrauterine pregnancy on the basis of absence of an intrauterine gestational sac. Two cases illustrating intrauterine echoes suggesting a gestational sac associated with ectopic pregnancy and a plausible explanation for this phenomenon are presented. Because of this and the rare possibility of coexisting intrauterine and extrauterine pregnancies, the ultrasonographer must be wary of dismissing the possibility of an ectopic pregnancy because of an intrauterine gestational sac, whether real or apparent.


Lateral decubitus position for demonstration of the aortic bifurcation. A technique for demonstrating the aortic bifurcation and proximal iliac arteries is presented. This technique is performed in the left lateral decubitus position and uses the right lobe of the liver as an acoustic window.


An analysis of pancreatic sonography in suspected pancreatic disease. To assess the value of pancreatic sonography in patients suspected of having pancreatic disease, our first 500 pancreatic examinations using gray scale imaging were reviewed in a prospective manner without clinical information. Various parameters of each examination were recorded. The pancreas was localized by its relationships to surrounding vessels and the duodenum. The ability to define the head, body, and tail of the pancreas as well as anterior--posterior size measurements were noted and recorded. A retrospective clinical pathologic follow-up was then carried out and correlated with the ultrasonic findings. Four categories of patients were identified. The features seen in pancreatic ultrasonography of the entire group, as well as those seen in the individual categories, were analyzed. This analysis indicates that pancreatic sonography can be used in patients suspected of having pancreatic disease, defining both normal and abnormal pancreas. A high index of suspicion for the type of abnormality present can be achieved.


Hepatitis Be antigen and antibody in hepatitis B surface antigen positive blood donors. In a study of 105 asymptomatic HBsAg positive blood donors, 9 (8.6%) were found to have HBeAg, 38 (36.2%) anti-HBe, and the remaining 58 (55.2%) neither marker detectable by gel diffusion. There was no correlation between HBeAg/anti-HBe status and HBsAg sub-types, Glm allotypes, the presence of anti-Gm, red cell antibodies, or rheumatoid factor. Rheumatoid factor activity could be removed from anti-HBe positive sera without removing anti-HBe activity, indicating that separate entities were involved. HBeAg was found only in donors under the age of 30 (P less than 0.005), while anti-HBe did not show an age-related trend. HBeAg was also found less commonly in donors of blood group A than in the total carrier population (P less than 0.05), indicating an apparent protection in carriers of group A. The blood group distribution for the 105 HBsAg positive donors was similar to that of the general population.


Rapid serotyping of groups A, B, and C meningococci by rocket-line immunoelectrophoresis and co-agglutination. Rocket-line immunoelectrophoresis (R-LIE) with antigen containing intermediate gel, and co-agglutination utilising protein A-containing staphylococci coated with specific antibodies, were adapted for serotyping the prototypes of group B meningococci. Both were found to have the same specificity as agar gel double diffusion (AGDD) but they were more sensitive and more rapid than AGDD. R-LIE required, like AGDD, the extraction of relatively large quantities of bacteria, while the co-agglutination method, performed as a slide agglutination tests with results within a few minutes and no need of special equipment, required only a small amount of heated whole meningococcal cells. Meningococcal strains of serogroups B, C, and A from patients with carriers were serotyped and the results with all three methods were in agreement.


Changes in the activity of lactose synthetase in the goat udder during pregnancy. The lactose synthetase activity of homogenates and particulate fractions prepared from the udders of goats killed at various stages of pregnancy were determined. Both components of the enzyme, galactosyltransferase and alpha-lactalbumin, became detectable about half way through the gestation period, at the time when rapid proliferation of mammary epithelial tissue commences. Throughout the second half of pregnancy the udder possessed a high level of lactose synthetase activity though the lactose content of the tissue did not increase. These findings are discussed in relation to the endocrine control of lactogenesis in the goat and possible mechanisms for the induction of milk production at parturition.


Compatibility of various materials with oral tissues. II: Pulp responses to composite ingredients. Eight ingredients of composite materials were evaluated individually for pulp irritation. None caused significant inflammation as evidenced by its average response. No abscess formations or lesions predominating in leukocytes occurred.


Aging in the rhesus monkey: effects on visual discrimination learning and reversal learning. The behavior of aged rhesus monkeys (18 years and older) was compared to that of young monkeys (3 to 6 years old) to evaluate their relative abilities to learn a series of visual discrimination and discrimination reversal problems. Using a subject-paced, automated experimental procedure designed to optimize stimulus control and facilitate execution of choice responses, no consistent age-related differences were observed in the ability to learn new color and pattern discrimination problems of varying difficulty. However, a severe and consistent deficity on reversal learning did occur. A detailed analysis of this deficit revealed that not only did the aged monkeys take longer to extinguish the old habit and return to chance performance, but they continued to display a deficit in establishing accurate performance at above-chance levels as well. Since no reliable age differences were observed on the original discrimination learning problems, these data suggest that aging impairs mechanisms involved with response rigidity and/or susceptibility to intertrial proactive interference, more severely than those involved with the simple formation of new associations.


A simplified procedure for measuring the class of anti-bacterial antibodies by mixed reverse passive antiglobulin haemagglutination (MRPAH). A modified procedure is described for performing the MRPAH (mixed reverse passive antiglobulin haemagglutination) reaction as a simple micro-method to measure the classes of bacterial antibodies. This 'bacterial dilution procedure' gave results closely correlated with those obtained by the 'serum (sample) dilution procedure' previously reported and with great economy of materials, labour and time. The method was used to investigate human serum antibodies to Br. abortus and S. enteritidis and serum and secretory antibodies to Strep. mutans. The good reproducibility of the MRPAH reaction was demonstrated by re-examining brucellosis sera tested one year previously. MRPAH was sufficiently sensitive to demonstrate the small amounts of IgG and IgM antibodies to Strep. mutans in human colostrum and early milk. A rise of antibody levels in the different immunoglobulin classes G, A and M was readily demonstrated in sera from individuals with salmonellosis.


Morphologic expression of the interactions of human lymphocytes and Pseudomonas aeruginosa as observed by scanning electron microscopy. When human lymphocytes and Pseudomonas aeruginosa were incubated together and then observed under the scanning electron microscope, four distinct morphologic observations were made: (1) filopods extending between lymphocytes and bacteria; (2) globular structures bulging out in many of the filopods; (3) filopods connecting lymphocytes to each other in the presence of bacteria; and (4) bacteria adhering to the lymphocytes in areas where decreased numbers of microvilli were present.


Comparative immunogenicity of vaccines prepared from capsular polysaccharides of group C Neisseria meningitidis O-acetyl-positive and O-acetyl-negative variants and Escherichia coli K92 in adult volunteers. Three structurally and antigenically similar capsular polysaccharides, two derived from group C Neisseria meningitidis (O-acetyl-positive and O-acetyl-negative variants) and one from Escherichia coli K92, which cross-reacts with polysaccharide from group C N. meningitidis, were compared for their ability to induce anticapsular and bactericidal antibodies to group C N. meningitidis in adult volunteers. All three vaccines elicited group C-specific serum antibodies. The vaccine derived from the O-acetyl-negative variant was the most immunogenic of the three vaccines. With use of radiolabeled O-acetyl-positive group C N. meningitidis polysaccharide antigen, the geometric mean titers of antibody in serum were 41.7 microgram/ml to the O-acetyl-negative variant, 22.8 microgram/ml to the O-acetyl-positive variant, and 7.1 microgram/ml to E. coli K92. Antibodies induced by all three vaccines were bactericidal for both of the group C N. meningitidis polysaccharide variants. An inverse relation between the comparative immunogenicity of the O-acetyl-negative polysaccharide and the virulence of group C N. meningitidis was found.


Studies on gonococcus infection. XVII. IgA1-cleaving protease in vaginal washings from women with gonorrhea. Vaginal washings from women attending a veneral disease clinic were examined for the presence of protease that cleaved IgA subclass 1 (IgA1). In a crude assay, vaginal washings cleaved [125I]IgA1 in 19 of 25 specimens from individuals from whom Neisseria gonorrhoeae were cultivated. Forty-six specimens from 104 women whose cultures were negative for N. gonorrhoeae also cleaved [125I]IgA1. Vaginal washings from six of six women with culture-proven gonorrhea cleaved [125I]IgA1 into low-molecular-weight components identical to those produced by partially purified IgA1-specific protease from gonococci. The hydrolysis of [125I]IgA1 by vaginal washings from women whose cultures were negative for N. gonorrhoeae yielded cleavage products that resembled those of trypsin or alpha-chymotrypsin. These findings indicate that gonococci residing in the female genital tract produce IgA1-specific protease that can be detected in the vaginal washings of infected women.


Transfer of multiple antibiotic resistance between subspecies of Bacteroides fragilis. Resistance to clindamycin, erythromycin, streptogramins, and tetracycline was shown to be transferable from a clinical isolate of Bacteroides fragilis subspecies distasonis to a sensitive strain of B. fragilis subspecies fragilis. Resistance to clindamycin, erythromycin, and streptogramins was transferable from a clinical isolate of B. fragilis subspecies fragilis to the sensitive strain of B. fragilis subspecies fragilis. Except for tetracycline, resistance to all of these antibiotics was spontaneously curable en bloc at a frequency of approximately 10(-2). These results suggest that resistance to these antibiotics is determined by a plasmid.


Experimental nasopharyngitis and pneumonia caused by Chlamydia trachomatis in infant baboons: histopathologic comparison with a case in a human infant. Three infant male baboons were inoculated with a strain of CHLAMYDIA TRACHOMATIS ISOLATED FROM A HUMAN INFANT WITH PNEUMONITIS. One baboon, inoculated by intratracheal, nasopharyngeal, and oropharyngeal seeding, had rales, radiographic evidence of pneumonia, persistent nasopharyngeal C. trachomatis infection, and a four-fold rise in titer of antibody. At sacrifice 24 days after inoculation, nasopharynx, trachea, airways, and lung yielded C. trachomatis, and epithelial inclusions were seen by light and immunofluorescent microscopy. Histopathologic changes noted were nearly identical to those in a lung biopsy specimen from a human infant and pneumonitis and nasopharyngeal C. trachomatis. The second baboon was inoculated by tracheal seeding and maintained nasopharyngeal C. trachomatis until killed 30 days later. Autopsy revealed nasopharyngitis and patchy mild pneumonitis. The third baboon was inoculated by nasopharyngeal seeding and maintained nasopharyngeal C. trachomatis for 49 days. Both of the latter baboons seroconverted. Infant baboons appear to be useful animal models for C. trachomatis nasopharyngitis and pneumonia.


Cynomolgus monkey model for experimental Q fever infection. A subhuman primate model was developed for study of the pathogenesis of infection with Coxiella burnetii. Cynomolgus monkeys (Macaca fascicularis) that were exposed to 10(5) mouse median infectious intraperitoneal doses of C. burnetii in a small-particle aerosol developed clinical signs of illness and pathologic changes characteristic of Q fever infection in humans. All monkeys had radiologic evidence of pneumonia by day 9. Antibodies to C. burnetii were detectable by the indirect fluorescent antibody test by day 7. These data indicate that the cynomolgus monkey is a suitable model for study of the pathogenesis of Q fever infection and may prove valuable in the evaluation of C. burnetii vaccines.


Influence of genetic factors on natural resistance of mice to Pseudomonas aeruginosa. In order to determine whether genetic background influences natural resistance to Pseudomonas aeruginosa, a series of 16 different strains of inbred mice were challenged intraperitoneally with P. aeruginosa. Significantly greater natural resistance to infection was found in mice of C3H background genome than in mice of A background genome. This phenomenon was documented for two different strains of P. aeruginosa but could not be demonstrated in control studies in which mice were intraperitoneally challenged with Staphylococcus aureus or Escherichia coli. The enhanced resistance of C3H mice was independent of currently defined haplotypes at the H-2 locus. The killing activity of serum against Pseudomonas was not greater in C3H mice than in A mice. The extension of these findings to disease in humans suggests that the particular susceptibility of certain populations of patients to Pseudomonas may be partially related to genetic factors.


Complement-enhanced immunity to infection with Neisseria gonorrhoeae in mice. Subcutaneous chambers were implanted in mice, injected with Neisseria gonorrhoeae, and supplemented with complement as a model for studying the immunogenicity and strain diversity of N. gonorrhoeae. Immunotypic resistance to N. gonorrhoeae in immunized mice was significantly (P less than 0.01) increased by injection of exogenous guinea pig complement into the host before challenge with gonococci. By using this model to test gonococcal isolates from various geographical areas, two highly immunogenic but immunotypically different gonococcal strains were identified. The piliated cells of these strains induced both complement-enhanced immunity and a degree of exogenous complement-independent immunity. The immunity in mice not treated with complement developed more slowly, was less effective, and waned earlier than that which was complement-dependent. Pretreatment with complement, although highly effective in preventing infection in immunized mice, was much less beneficial in terminating already established infections, even though bactericidal antibodies were present at the time of complement treatment. The mouse chamber model in which both complement-mediated and complement-independent mechanisms of protection can be evaluated may provide an additional tool for elucidating the immunology of gonococcal or other microbial infections.


Minimal antibiotic concentrations of aminoglycosides and beta-lactam antibiotics for some gram-negative bacilli and gram-positive cocci. The minimal antibiotic concentration (MAC) is the lowest concentration of an antibacterial agent that produces a decrease of 1 log in the number of organisms/ml as compared with a control culture in drug-free medium. Various gram-negative bacilli and gram-positive cocci were grown in the presence of amikacin, gentamicin, tobramycin, ampicillin, amoxicillin, oxacillin, carbenicillin, ticarcillin, and cefamandole at concentrations varying from eight times the minimal inhibitory concentration (MIC) to 1/128 of the MIC. Colony forming units (cfu) were counted, the MIC was determined, and the MIC:MAC ratio, which indicates the magnitude of the effective range, was calculated. The MIC:MAC ratio appears to be characteristic for a given species and antibiotic. There is no relation between the MICs and the MIC:MAC ratios. The highest ratios were given by Proteus mirabilis with aminoglycosides (MIC:MAC mean, 29.2 with tobramycin), and the lowest ratios were given with beta-lactam antibiotics by Pseudomonas aeruginosa and Streptococcus faecalis (MIC:MAC means, 2.1 with carbenicillin and cefamandole, respectively).


Biosynthesis of glycosylated hemoglobins in the monkey. We have investigated the in vivo biosynthesis of the minor hemoglobin components in the rhesus monkey. The elution profile of rhesus hemolysate on BioRex 70 cation exchange resin was analogous to that of human hemolysate. The rhesus Hb Alc peak was identified with the TBA test, which revealed a carbohydrate content identical to that of human Hb A1c. A rhesus monkey was injected with autologous 55Fe-bound transferrin, and the specific activity of each of the minor and major components was followed for over 70 days. As previously shown in man, rhesus Hb alc accumulated specific activity almost linearly over the erythrocyte life-span, indicative of slow and continuous conversion of Hb A0 to Hb Alc. This study revealed two new findings. (1) The specific activity of rhesus Hb Alb was always significantly less than that of Hb Alc. This result suggested that HB Alb is made by further posttranslational modification of Hb Alc. (2) The first portion of rhesus Hb A0 to be eluted on BioRex 70 contained a significant amount of carbohydrate and lower initial specific radioactivity than did the latter portion. This unexpected heterogeneity in the major hemoglobin component reflects slow, nonenzymatic glycosylation at sites other than at the N-terminus of the beta-chain.


Otolaryngological features of 'malformation syndrome with cryptophthalmos'. Anomalies of the nose, larynx and oral cavity are described in two patients with cryptophthalmos. A teratogen acting at the time of lid fold formation is probably responsible for the ocular and systemic involvement which are primarily ectodermal defects with some mesodermal involvement.


Adipose tissue development, growth, and food consumption in protein-malnourished rats. Effects of protein malnutrition on adipose tissue development were studied in weanling male Sprague-Dawley rats fed isocaloric diets ad libitum containing either 22% (controls) or 8% (protein-malnourished rats) casein, and in rats pair-fed to the protein-malnourished rats with the 22% casein diet. After 32 days on the diet, protein-malnourished rats were 37% and pair-fed 67% the weight of the controls, while torso length was 37% and 73% of controls, respectively. Food consumption relative to body weight was greatest in protein-malnourished rats. Compared to control rats, the distal epididymal adipocyte number in the protein-malnourished rats was decreased in proportion to the decrease in body size and was more closely related to the protein intake than to the total calories consumed. After 32 days on diet, mean adipocyte number per 2 distal pads was 11.7 x 10(6) in controls and 4.3 x 10(6) in protein-malnourished rats. In pair-fed rats, cell number lagged behind controls at 4 and 11 days, but was normal at 32 days (11.4 x 10(6) cells). The distal epididymal pad adipocyte size and percent lipid were similar in all groups during the first 25 days of dietary treatment. Adipocyte size was increased significantly in controls at day 32 compared to the other two groups. At each time studied through day 25 on diet, epididymal pad weight was related to the adipose cell number rather than the cell size. It is concluded that severe restriction of dietary protein during the postweaning period of growth in rats results in decreased epididymal adipocyte proliferation and/or differentiation concomitant with generalized growth retardation, whereas isocaloric feeding of a diet of normal protein content is associated with only a transient delay in adipose tissue development.


Transport of thyroxine in the serum of vitamin A-deficient rats. Thyroxine (T4) transport in the serum of rats deficient in vitamin A was studied by electrophoresis after incubation of serum samples with radioactive T4. In serum from vitamin A-deficient rats, the amount of radioactivity bound to the prealbumin zone of the electrophoretograms decreased, whereas there was an increase in the amount of radioactivity bound to the albumin zone. The serum from vitamin A-deficient rats subsequently fed a normal diet (repletion experiment) had an electrophoretic pattern similar to that of normal rats. The serum fraction which bound radioactive T4 appeared in the prealbumin rather than the albumin zone. These results suggest that vitamin A deficiency causes an early change in the transport of thyroid hormones in the plasma and a new level of serum thyroxine which may be responsible for the biochemical and physiological changes which occur in vitamin A-deficient rats.


Interrelation of the pituitary-thyroid system at birth in man. Samples of cord blood derived from 105 normal babies after uncomplicated deliveries were assayed for thyroxine (T4), tri-iodothyronine (T3), reverse tri-iodothyronine (rT3), thyroxine-binding globulin (TBG) and thyrotrophin (TSH). The values for T3, rT3 and TSH were log-normally distributed (geometric means 0.62 nmol/l, 3.28 nmol/l and 10.9 mu./l respectively) and those for T4 and TBG were normally distributed (means 126 nmol/l and 13.7 mg/l), The data were systematically analysed and no evidence was obtained to suggest that the concentration of TSH, which varied widely, was regulated by any of the thyroid hormones alone or in combination. There was a direct relation between the concentrations of T4 and T3 in the cord blood at birth but not between either of these and rT3. There is thus no evidence of a functional interdependence of the hypothalamic-pituitary-thyroid system in man at birth.


Temperature-related changes in the erythrocytic carbonic anhydrase (acetazolamide-sensitive esterase) activity of goldfish, Carassius auratus. 1. Carbonic anhydrase activity in 'membrane' and 'cytosol' fractions of goldfish erythrocytes was assayed by the p-nitrophenyl acetate procedure following thermal acclimation. 2. The thermal sensitivity of "membrane"-associated activity was apparently unaltered by acclimation. "Cytosol" activity in warm-acclimated specimens was somewhat more thermosensitive than that animals maintained at low temperature. 3. Significant increases in specific activity, and activity per unit volume of packed cells and blood were observed at higher temperatures when assays were conducted at the temperatures at which the system actually functions in the fish. By contrast, when determinations were carried out at a standard temperature (41 degrees C) corresponding to the upper incipient lethal for this species, activity was either unaffected, or declined as acclimation temperatures increased. 4. Changes in carbonic anhydrase activity following acclimation are consistent with the hypothesis that this system is implicated in the maintenance of stable plasma chloride levels, and the suggestion that alternations in red cell chloride levels with temperature are, in part at least, attributable to concomitant variations in enzyme activity.


[Evidence of type-specific microheterogeneity of thyroxine-binding globulin by isoelectric focusing (author's transl)]. A rapid method for the isolation of the thyroxine-binding globulin from only 150 ml plasma is described. The preparation of a high-activity thyroxine-sepharose is essential; this contained L-thyroxine bound exclusively by covalent linkage. Furthermore, the elution of the protein was performed under specifically hydrophobic conditions. Using isoelectric focusing on 15 individual preparations of thyroxine-binding globulin, and densitometric analysis of the polyacrylamide gels, it was possible to show three protein bands in different proportions according to the individual. Three distribution-types were found in the tested volunteers. The results of this investigation show that these types are individual-specific, whereas there are no apparent sex-specific differences.


On the mechanism of the amiloride-sodium entry site interaction in anuran skin epithelia. The steady-state transport kinetics of the interaction between external sodium and the diuretic drug, amiloride, was studied in isolated anuran skin epithelia. We also investigated the effect of calcium on the amiloride-induced inhibition of short-circuit current (Isc) in these epithelial preparations. The major conclusions of this study are: (a) amiloride is a noncompetitive inhibitor of Na entry in bullfrog and grassfrog skin, but displays mixed inhibition in R. temporaria and the toad. A hypothesis which states that the interaction sites for amiloride and Na on the putative entry protein are spatially distinct in all of these species is proposed. (b) The stoichiometry of interaction between amiloride and the Na entry mechanism is not necessarily one-to-one. (c) The external Ca requirement for the inhibitory effect of amiloride is not absolute. Amiloride, at all concentrations, is equally effective in inhibiting Isc of bullfrog skin independently from the presence or absence of external Ca.


Mutants of Bacillus subtilis affected in spore outgrowth. Six mutants of Bacillus subtilis 168 that are temperature-sensitive in spore outgrowth were isolated. The outgrowth process proceeds normally at 35 degrees C, but at the non-permissive temperature (47 degrees C) it is arrested at a specific stage characteristic for each mutant strain. The mutants are not altered in vegetative growth whether at 35 degrees C or at 47 degrees C. They were characterized for their ability to synthesize RNA, proteins and DNA during outgrowth. A mutant defective in spore germination was also isolated; less than 5% of its spores can germinate at any of the temperatures tested. The mutations were mapped by means of transduction and transformation. The isolation of a number of outgrowth mutants which map at different loci and which affect outgrowth at different times is discussed in relation to the regulation of this process.


A Bacillus subtilis mutant requiring dipicolinic acid for the development of heat-resistant spores. A Bacillus subtilis mutant is described which forms heat-resistant spores only in the presence of external dipicolinic acid (DPA). The mutation, dpa-1, is localized in a new sporulation locus, linked to pyrA. The dpa-1 strain is unable to synthesize DPA but can incorporate external DPA. The amount of DPA incorporated, the frequency of heat-resistant spores and their degree of resistance are all dependent on the concentration of external DPA. Spores of dpa- 1 strains exhibit normal resistance to most chemicals, including octanol and chloroform, but not to ethanol, pyridine, phenol and trichloroacetic acid. Complete resistance to the latter group depends on DPA. DPA incorporation is slow and apparently requires an energy supply but not protein synthesis. Direct involvement of DPA in the heat-resistance of the spores is suggested. Thin sections of DPA-less spores exhibit clearly visible cytoplasmic membranes and ribosomes. These structures are absent or less visible in the core of spores obtained with added DPA.


Decadent sporulation mutants of Bacillus subtilis. In decadent sporulation mutants, sporulating populations are heterogeneous: the cells reach successive chemical and physical resistances with progressively decreasing frequencies. Each decadent mutant can be characterized by the shape and slope of the curve describing the frequency of cells resistant to various agents ('the resistance spectrum'). In some mutants the resistance spectrum decreases progressively from xylene resistance to heat resistance; in other mutants it decreases rapidly between octanol resistance and chloroform resistance. Electron microscopy showed that in two mutants the majority of the cells are blocked at stages III and IV; the number of cells that develop further to reach successive morphological stages falls off progressively. In two other mutants most cells reach stage V. Cortexless spores are also frequent. One of the decadent mutations, SpoL1, was localized between aroD and acf. The phenotype of decadent mutants is discussed in terms of sequential gene activation.


Muscle satellite cells in malnourished and nutritionally rehabilitated children. Satellite cells were examined qualitatively and quantitatively in muscle biopsies from children when malnourished, during nutritional rehabilitation, and after clinical recovery. The proportion of satellite cell nuclei relative to myonuclei was significantly lower in malnourished subjects than in well-nourished age-matched controls (4.5 +/- 1% vs. 8.1 +/- 1.0%). The proportion of satellite cells remained low during the early period of "catch-up growth" but was significantly increased in the recovered subjects (10.5 +/- 1.0%). Satellite cells were small and their nuclei were heterochromatic in biopsies from the malnourished subjects. The cells were often partially segregated from the parent fiber by an external lamina. In recovering and recovered subjects many of the satellite cells enlarged, and the appearance of their nuclei and cytoplasmic organelles suggested a more active state. Intervention of external lamina between the satellite cell and the myofibre was uncommon in the recovered subjects.


[Hereditary motor neuron disease: the proximal, adult, sex-linked form (or Kennedy disease). Clinical and neuroendocrinologic observations]. Clinical, electrophysiological, histological and neuroendocrinological findings in a peculiar form of progressive spinal and bulbar muscular atrophy affecting 4 members in two different families are reported. The clinical hallmarks, which characterize this entity among the group of degenerative motor neuron diseases are: sex-linked recessive inheritance; onset in the third decade; slow progression; involvement of facial and bulbar muscles in addition to wasting of the proximal and, in some cases, the distal musculature; asymmetry of clinical signs; consistent and abundant fasciculations predominantly in the peri-oral muscles; intention tremor and a well-developed gynaecomastia, which is the first clinical sign. Electrophysiological and histological findings confirm the neurogenic origin of the muscular atrophy; in addition, muscle biopsy shows "myopathic-like" changes in one case and serum muscle enzyme levels are elevated in all neurologically affected patients. It is believed that the clinical entity corresponds to the rare type III proximal hereditary motor neuropathy (or "Kennedy's disease"), of which 25 published cases are reviewed. Neuroendocrinological data in two patients demonstrate an androgenic insufficiency of hypothalamo-hypophyseal origin and high levels of circulating oestrogens, which probably have induced gynaecomastia. Dynamic neuroendocrinological tests suggest that lesions of certain hypothalamic nuclei may exist, which should be looked for in the forthcoming anatomical studies.


The effect of dietary sulfur-containing amino acids on the activity of drug-metabolizing enzymes in rat-liver microsomes. Male Wistar rats were fed either a balanced diet whose protein source was a mixture of amino acids (diet 1), or a similar diet which differed only in having 48% less the quantity of the sulfur-containing amino acids methionine and cystine (diet 2). The diets were given either continuously for 1 month or for 15 days after a protein-free diet. Both diets 1 and 2 permitted good growth of rats and relatively stable microsomal protein content. Protein depletion decreased the total proteins, total phospholipids, and cytochrome P-450 content, and it strongly increased UDP-glucuronosyltransferase activity in rat-liver microsomes. Repletion with diet 1 restored those values, to the level found in control rats. However, diet 2, given continuously induced an increase in UDP-glucuronosyltransferase activity and in the cytochrome P-450 concentration. Since high UDP-glucuronosyltransferase activity was related to lessened amounts of sulfur-containing amino acids in the diet, we discuss the possible effect of methionine and cystine on the regulation of glucuronoconjugation in relation to sulfoconjugation.


Effects of quantity and unsaturation of dietary fat on serum components in normal and diabetic Macaca nigra. Dietary fat affects serum lipids independently of dietary cholesterol. Normal and diabetic monkeys (Macaca nigra) were fed cereal-based, specially formulated diets with either a low fat (LF = 2.5%) or a higher fat (13.2%) content; the latter had varying concentrations of safflower and coconut oil to attain greater polyunsaturation (SFO) or saturation (CCO) in the diets. Dietary cholesterol was less than 0.01%. Serum triglyceride concentrations were greatest when monkeys consumed the LF (higher carbohydrate) diet and lowest when they consumed the SFO diet. Concentrations were greater in diabetic than in normal monkeys fed the LF and SFO diets, but both groups had similar concentrations when fed the CCO diet. Cholesterol levels in diabetic monkeys were only slightly higher than in normals regardless of diet; in both groups, levels were lowest when the LF diet was fed and highest when the CCO diet was fed. The quantity of fat had a greater effect on serum cholesterol than did the degree of polyunsaturation. In both groups, triglyceride concentrations correlated significantly with VLDL protein, and cholesterol levels correlated with LDL protein. Thus the responses of Macaca nigra to dietary fat manipulation depend upon both the diet fat content and composition as well as the normal or diabetic metabolic state of each monkey.


Determination of intravenous non-protein energy and nitrogen requirements in growing rats. Two experiments were conducted to estimate total non-protein energy and nitrogen requirements in growing healthy male Wistar rats nourished by parenteral nutrition. In experiment 1, non-protein energy varying from 30 to 70 kcal/day/rat were administered to animals receiving a constant dose of 80 mg nitrogen, plus vitamins and minerals. In experiment 2, nitrogen dosages varying from 0 to 280 mg N/day/rat with a constant dose of 60 kcal non-protein energy were studied. The formulation of the amino acid solution used in both experiments was based upon recommended oral amino acid requirements for growing rats. Dextrose served as the source of non-protein energy. Weight gain and nitrogen balance during a 6-day experimental period were used to determine requirements. Plasma free amino acids were also analyzed to evaluate the amino acid solution. Results indicate that under total parenteral nutrition conditions 578 to 621 mg/kg body weight3/4 nitrogen and 171 to 182 kcal/kg body weight3/4 non-protein energy are required to achieve growth of approximately 3 g/day. Inconsistent responses of plasma amino acid concentrations to the amounts infused were observed. It is suggested that the determined requirements can be applied as guidelines to research using the rat as an animal model in total parenteral nutrition.


Advances in epithelial kinetics--an oral view. There is growing evidence that the basal layer of stratified squamous epithelia consists of cells of differing proliferative capacities and behaviour. These can be classified as stem cells, transient amplifying cells and post-mitotic maturing cells, the most important of which appear to be the stem cells which may be present throughout life and are responsible for all cell production under steady-state conditions. Recent stem cell concepts are reviewed for epidermis, intestinal crypt and oral mucosa and are compared with tissues such as bone marrow and testes which have for some time been thought to operate in a similar manner. These concepts are applied to several pathological conditions of oral epithelia in an attempt to explain some of the changes observed.


An oral lesion in tobacco-lime users in Maharashtra, India. The habit of chewing tobacco along with lime in the canine-premolar region of the mandibular groove is widespread (28%) in the rural population of Maharashtra, India. Among individuals with this habit, a thick yellowish-white-to-brown lesion was observed at the site of placement of the mixture. Unlike leukoplakia, this lesion could be scraped off. The prevalence of this lesion among 101,761 Maharashtrian villagers was 2.9% which is four times more common than leukoplakia (0.67%). It is surmised that this particular lesion among the tobacco-lime users is a specific entity with consistent histological features. The diagnosis should be made on the basis of history, clinical features, and consistent histological picture.


Oral lesions in renal transplant patients. Plaque-like lesions of the oral mucosa have been observed in seven immunosuppressed renal transplant patients. Whilst bearing a superficial resemblance to acute pseudomembranous candidiasis (thrush), these lesions have been shown to be associated with bacterial overgrowth and not with fungi. Treatment has depended on the use of appropriate antibiotics and antiseptics together with the adoption of measures to cause disintegration of the mucoid matrix of the lesions.


A new method of sterilization: the carbon dioxide laser. The use of the carbon dioxide (CO2) laser for sterilization of metal instruments was investigated. Scalpal blades contaminated with bacterial spores were exposed to the laser and subsequently cultured. Our results demonstrate that the CO2 laser effectively sterilizes metal instruments.


Angiolymphoid hyperplasia with eosinophilia. Angiolymphoid hyperplasia with eosinophilia is a recently recognized lesion of skin consisting of atypical vascular paroliferation and variable inflammatory cell infiltration. A case is described here of a similar lesion presenting as an intraoral swelling. In addition to showing the histological features generally associated with angiolymphoid hyperplasia with eosinophilia, the present case exhibited striking smooth muscle proliferation.


Histopathologic and bacterial evaluation of conventional and new copper amalgams. In vivo pulpal responses in monkeys and in vitro bacterial inhibition studies were completed on new copper amalgams, Sybraloy, Dispersalloy, Tytin and a conventional Spheraloy amalgam. Amalgams were placed in cavities lined with ZOE and in unlined cavities. Silicate and ZOE were used as controls. A total of 165 adult monkey teeth were evaluated at 3 days, 5 and 8 weeks. At 3 days the pulpal responses elicited by the copper amalgams appeared similar to conventional Spheraloy, all showing a slight to moderate response. At 5 weeks the majority of amalgams exhibited a slight pulpar response with a tubular reparative dentin under each restoration. The 8 week pulpal response showed a reduction of the inflammatory response characterized by a tubular reparative dentin with a uniform zone of predentin. Lined ZOE controls exhibited a slight response while silicate showed a moderate response with some persistent chronic inflammation. In vitro bacterial tests revealed that the various amalgams had little to no inhibitory effect on the three serotypes of S. mutans that are most prominent in humans.


Electron microscopic investigation of hyaline bodies in odontogenic cysts. With the light microscope, hyaline bodies of Rushton may appear lamellar or granular. In this investigation, the ultrastructures of both lamellar and granular forms were studied in formalin fixed material, and in specimens fixed in osmium tetroxide. The lamellar type was composed of alternating electron dense and electron lucent layers, the outermost layer always being electron dense. The granular type was composed of amorphous material in which fragments of red blood cells could be seen. Some hyaline bodies were partly granular and partly lamellar. The surfaces of the epithelial cells apposed to both types showed large numbers of hemidesmosomes, but no basal lamina was seen. The amorphous material in the granular hyaline bodies appeared very similar to the substance of the degenerating red blood cells, and extravasated red cells were commonly found in the adjacent connective tissue. The results suggest that the granular type is formed from degenerating red blood cells, and that the lamellar pattern may result from segregation of components within the mass rather than by an incremental form of growth. No support was found for the hypotheses that hyaline bodies are keratinous or a secretory product of the epithelial cells.


Microscopic changes in rat tongue following experimental cryosurgery. Histological changes were studied in the rat tongue for varying periods of time up to 14 days following the application of a cryoprobe to the dorsal surface of rat tongue. Within minutes of the application, focal subepithelial vesiculation and hyperemia occurred. At 3 h there was evidence of damage to capillary walls, resulting in hemorrhage. Arterioles and venules were thrombosed and there were degenerative changes in the muscle layer of their walls. At 6 h ventral epithelium showed evidence of damage. At this stage vessel walls were pavemented with neutrophilic polymorphonuclear leukocytes (PMN) and some of the latter were seen in the vessel walls. At 24 h abundant PMN, many of them necrotic, were present in the vessel walls, apparently unable to pass through them. At 48 h numerous PMN were seen adhering to degenerating muscle fibers. By 4 days necrotic changes extended through the full thickness of the tongue, but concurrently it was observed that the larger thrombosed vessels were becoming recanalized. At 5 days repair by granulation tissue was taking place and at 6 days the vasculature was virtually reconstituted. By 14 days healing was complete.


Plasma naltrexone kinetics after intravenous bolus administration in dogs and monkeys. This investigation generated data characterize a specific electron-capture GLC assay reported previously for naltrexone and applied the method to a determination of naltrexone pharmacokinetics. Extraction efficiencies are reported for the assay, and mass spectral evidence indicates that naltrexone forms a triester when derivatized for electron-capture GLC with pentafluoropropionic anhydride and a base catalyst. Plasma level-time data for intravenous naltrexone at two dose levels in monkeys yielded no evidence of dose-dependent kinetics. A two-compartment open pharmacokinetic model was fitted to plasma level-time data for naltrexone in two dogs and yielded a total body clearance of 51-55 ml/min/kg. Urine collected for 0-24 hr contained 36% of the dose as naltrexone conjugates with less than 1% as unchanged naltrexone. Plasma level-time data for intravenous naltrexone in six monkeys yielded an average terminal half-life of 7.8 hr and a total body clearance of 64 ml/min/kg. The total body clearance for naltrexone was greater than the hepatic plasma or blood flow in both dogs and monkeys. This finding, together with the extremely low renal excretion of naltrexone, suggests the existence of elimination mechanisms besides liver metabolism and renal excretion.


Rapid and accurate stability-indicating assay for nitroglycerin. A rapid high-pressure liquid chromatographic method for determining the nitroglycerin concentration in liquid dosage forms and intravenous admixture solutions is presented. A coefficient of variation of less than 1.8% was achieved over the concentration range most commonly encountered (50-500 microgram/ml). A variable wavelength detector (lambda = 218 nm) and a micro-alkyl phenyl column were employed. The mobile phase was acetonitrile-tetrahydrofuran-water (26:10:64). Total analysis time was 12 min.


Effect of N-trifluoroacetyl derivatives of amino acids and amino acid analogs on microbial antitumor screen. Eighteen trifluoroacetyl derivatives of amino acids and of amino acid analogs were prepared and tested for growth-inhibitory activity using a Lactobacillus casei system as a prescreen for antitumor activity. Of the compounds tested, the trifluoroacetyl derivatives of o-, m-, and p-fluorophenylalanine and of beta-3-thienylalanine showed modest activity; trifluoroacetyl derivatives of phenylalanine and of beta-2-thienylalanine showed marginal activity. The activity exhibited by the active trifluoroacetyl compounds was equal to that noted for most active chloroacetyl derivatives reported previously, as judged by comparison of their activity with that of chloroacetyl-m-fluorophenylalanine. No reversal of inhibition was noted when a representative of these inhibitors was challenged with a corresponding natural metabolite, both as a free amino acid and as a noninhibitory acylated compound.


Congenital absence of lateral rectus muscle. A four-year-old female presented with a 60 PD left esotropia and Axenfeld's anomaly OU. Cosmetic strabismus surgery was undertaken, at which time it was discovered that the left lateral rectus was absent. The medial rectus was recessed, without change in the esotropia. At a second procedure six months later, the superior and inferior rectus muscles were transposed to the area of the missing lateral rectus. Follow-up examination revealed an 8 PD left esotropia with full ductions.


Effects of morphine, diazepam and chlorpromazine on discrimination of electric shock. The effects of morphine, diazepam and chlorpromazine were examined on the discrimination of electric shock in squirrel monkeys. Two discrete responses measured discrimination of the presence or absence of shock at two different intensities, either at 0.35 mA or at an intensity determined to be close to each monkey's threshold (0.05 or 0.15 mA). The percentage of responses which were correct in the presence and the absence of shock were determined separately. Time to respond to the presence or the absence of shock was also determined. Morphine decreased the percentage of correct responses at both the lower (0.05--0.15 mA) and the higher (0.35 mA) shock intensities, although effects at the higher intensity were very slight. Morphine had little effect on correct responses in the absence of shock. In contrast, diazepam decreased the percentage of correct responses in the absence of shock without affecting correct responses in the presence of shock, and chlorpromazine decreased the percentage of correct responses both in the presence and absence of shock. All three drugs increased time to respond both to the presence of shock and to the absence of shock with chlorpromazine producing the largest increase. Only morphine increased time to respond in the absence of shock more than in the presence of shock.


Rhodotorulic acid--investigation of its potential as an iron-chelating drug. The use of rhodotorulic acid (RA) as an iron-chelating drug was suggested by experiments in hypertransfused rats in which urinary and fecal iron excretion were significantly enhanced in response to RA. The toxicity of the drug appears to be minimal at a parenteral dose less than 250 mg/kg. An increased excretion of zinc was the only notable side effect of the drug at the doses used. When administered i.v. to humans, RA was only 16% more effective than desferrioxamine (DF). Pharmacokinetic studies showed that RA persisted in the bloodstream of dogs 6 times longer than desferrioxamine after an intravenous injection. Accordingly RA was evaluated as a potential repository drug. While animal experiments were encouraging, human subjects experienced a painful local reaction to RA administered either i.m. or s.c. as a suspension in physiological saline. Accordingly it appears that RA is best looked at as a second line drug, unless a means can be found to obviate local inflammatory reactions.


Characteristics of histamine H1-receptors in peripheral tissues labeled with [3H]mepyramine. Specific binding of [3H]mepyramine to membranes of various peripheral tissues of different species has been demonstrated. Drug specificity indicates an association with histamine H1-receptors. Of all the tissues examined brain contains the highest numbers of binding sites, while substantial levels of specific [3H]mepyramine binding are also demonstrable in some species in heart, lung, adrenal and ileum. Negligible specific [3H]mepyramine binding is observed in the liver, stomach and uterus of several species. The lesser bronchoconstricting response of the rat than of other species to histamine is paralleled by a lower number of [3H]mepyramine binding sites in rat lung than in other species. However, similar numbers or [3H]mepyramine binding sites occur in ileal membranes of rat, guinea pig and rabbit, although contractile effects of histamine vary in these species. In the quinea-pig ileum, [3H]mepyramine binding is most concentrated in the longitudinal muscle itself where histamine exerts its predominant contractile effects. In the bovine adrenal gland, [3H]mepyramine binding is more abundant and has higher affinity for drugs in the medulla than in the cortex.


Field potentials and excitation of primate spinothalamic neurones in response to volleys in muscle afferents. 1. In anesthetized monkeys, stimulation of muscle afferents results in a sequence of cord dorsum potentials. These include a group I volley followed by several negative potentials called here the NI, NII and NIII waves. 2. Evidence based on the effects of graded stimulus strengths, measurements of latencies, and the results of anodal blockade of large muscle afferents indicate that the NI, NII and NIII waves are evoked, respectively, by group I, II and III muscle afferents. 3. The NII and NIII waves appear to be confined to the lumbosacral enlargement when evoked by hind limb muscle afferents. However, the group I volley and NI wave can be detected at least as far rostrally as L 3. 4. The NII and NIII waves were mapped in the depth of the cord. The maxima for these waves were found in the neck of the dorsal horn. The waves reversed to become positive in the ventral horn. 5. Using graded electrical stimulation of muscle nerves it was possible to demonstrate that a few spinothalamic tract neurones could be activated monosynaptically by group I volleys; other spinothalamic cells may have been activated polysynaptically by group I volleys. The lack of any substantial excitation of spinothalamic neurones by intra-arterial injections of succinylcholine suggests that these group I actions may have been due to group Ib afferents from Golgi tendon organs. 6. The most potent excitation of spinothalamic tract cells was due to the action of middle sized and small muscle afferents. Evidence was obtained for an excitatory action of group II, III and IV afferents. There was a good correlation between the effects of graded stimulation in evoking discharges in separate bursts associated with the arrival of volleys in group II and group III afferents and the generation of the NII and NIII waves. 7. Some spinothalamic neurones, including several located in lamina I, were unaffected by the muscle afferent volleys used. It is suggested that such neurones might help to signal well localized pain, whereas the cells which respond to a variety of cutaneous and muscle afferents might be involved in signalling poorly localized pain which is subject to referral.


Effects of mechanical and chemical stimulation of fine muscle afferents upon primate spinothalamic tract cells. 1. Injections of algesic chemicals were made into the arterial circulation of the triceps surae muscles in anaesthetized monkeys. 2. The responses of a sample of primary muscle afferents suggest that what is known about the activation of muscle afferents in the cat by algesic agents applies also to the monkey. One exception to this is the activation of many group I afferents by KCl in the monkey, but not in the cat. 3. Many spinothalamic tract cells were powerfully excited by the intra-arterial injection of algesic chemicals (bradykinin, 5-hydroxytryptamine (5-HT), KCl) in preparations in which the hind limb was denervated except for the nerves to the triceps surae muscles. The excitatory action of bradykinin had a slower time course than did that of 5-HT or KCl. 4. A number of the spinothalamic tract cells which failed to respond to chemical activation of muscle afferents were located in lamina I of the spinal cord. 5. Repeated injections of bradykinin produced similar responses, whereas the effects of 5-HT injections showed marked tachyphylaxis. 6. No evidence was obtained that activation of muscle spindle afferents by succinylcholine injections resulted in the excitation of spinothalamic tract neurones in the population sampled. 7. Injections of hypertonic NaCl into muscle or tendon produced a prolonged excitation of many spinothalamic tract cells. 8. It is concluded that a substantial proportion of primate spinothalamic tract cells receive a convergent input from cutaneous and muscle receptors. The muscle receptors involved appear to include primary afferents of group III and IV calibre. The possibility is suggested that such cells could play a role in the production of poorly localized pain.


The depolarizing afterpotential of crab muscle fibres. A sodium-dependent process mediated by intracellular calcium. 1. A study was made of the depolarizing afterpotential (d.a.p.) which follows the initial graded electrogenesis of crab muscle fibres. 2. Increasing the strength, duration or amplitude of the stimulating current pulses enhanced both the d.a.p. and the local contractions. 3. Arsenazo III was injected intracellularly and changes in light absorbance by the dye were used to monitor the increase in free sarcoplasmic Ca concentration during excitation-contraction (E-C) coupling. The onset of the absorbance changes occurred during the depolarizing phase of the initial electrogenesis and the maximum value coincided with the peak of the d.a.p. An exponential decay of the absorbance signal occurred during the repolarizing phase of the d.a.p. 4. Ionophoretic injection of EGTA into the sarcoplasm did not affect the initial electrogenesis but did reduce changes in dye absorbance, blocked tension development and abolished the d.a.p. 5. Caffeine (0.1--0.4 mM) markedly enhanced both the d.a.p. and the local contractions, but had no effect on the initial electrogenesis. 6. Replacement of extracellular Na ions with Li, Tris or choline abolished the d.a.p. The initial electrogenesis was enhanced in the choline-containing medium, but was not affected by Li or Tris. The rate of relaxation of the local contractions and the rate of decay of the light absorbance changes were slowed in Na-free saline. 7. Tetrodotoxin (10(-5) g/ml.) had no effect on either the membrane responses or tension development. 8. For initial graded responses of comparable peak amplitude a threefold reduction of [Ca-a1o shortened the d.a.p., but had little effect onits peak amplitude. A fivefold increase in [Ca]o reduced both the amplitude and duration of the d.a.p. 9. Changes in [Mg]o had little effect on the d.a.p., but both Mn (4--10 mM) and La (0.1 mM) blocked the initial electrogenesis and the d.a.p. 10. It is concluded that distinct ionic mechanisms give rise to the initial electrogenesis and the d.a.p. While the former is due to activation of Ca conductance, the d.a.p. is a Na-dependent phenomenon that is tetrodotoxin-insensitive, and mediated by the rise of intracellular Ca concentration during E--C coupling.


Characteristics of the internal anal sphincter and the rectum of the vervet monkey. 1. The physiology of the internal anal sphincter of the vervet monkey was investigated. 2. Strips of sphincter in vitro contracted to noradrenaline and adrenaline; adrenoceptors were mainly alpha-excitatory. Strips of rectal circular muscle relaxed to noradrenaline and contained both inhibitory alpha- and beta-adrenoceptors. 3. All strips contracted to acetylcholine. After hyoscine or atropine, high doses of acetylcholine relaxed all strips by stimulating intramural inhibitory neurones as relaxations were blocked by tetrodotoxin and hexamethonium. Nicotine and DMPP gave relaxations with similar characteristics. 4. It was concluded that relaxations to acetylcholine, nicotine and DMPP were not adrenergic as relaxations still occurred in strips from sympathetically denervated or reserpinized animals. The block of these relaxations by propranolol and guanethidine was considered to be unrelated to their actions as adrenergic blocking drugs. 5. All strips relaxed to field electrical stimulation (1--5 Hz) through stimulation of intramural inhibitory neurones as tetrodotoxin blocked these relaxations. Adrenergic blocking drugs, prior reserpinization or prior section of the hypogastric nerves did not block these responses. The relaxations were not therefore adrenergic. 6. 5-Hydroxytryptamine relaxed all strips but was not the transmitter in relaxations to acetylcholine, DMPP or nicotine, nor to field electrical stimulation, as desensitization of strips of 5-HT did not alter these responses. 7. The circular smooth muscle of the internal anal sphincter had a dense terminal adrenergic innervation which rapidly decreased orad. 8. In vivo, hypogastric nerve stimulation relaxed the rectum but contracted the sphincter. Sacral nerve root stimulation caused an after-contraction in both rectum and sphincter. In vivo, a close arterial injection of adrenaline or noradrenaline inhibited the spontaneous contraction waves of the rectum, but contracted the sphincter. Both these responses were blocked by phentolamine. 9. It was concluded that the internal anal sphincter is a discrete high pressure zone which was excitatory cholinergic and adrenergic innervations and an inhibitory non-adrenergic innervation.


Porous titanium tooth roots: clinical evaluation. 1. An inert porous vehicle can be successfully used to attach endosseous dental implants to surrounding alveolar bone. 2. Implant size and the width of keratinized gingiva surrounding the implant are critical to the success of the implant. 3. Radiography and pocket depth are useful indicators of the status of porous endosseous roots, while mobility is not.


A variation of the endosseous blade-vent implant. This study demonstrates that it is possible to use a section of tooth root to achieve a connective tissue barrier to oral epithelium and oral bacteria. It appears that the reattachment gained is very susceptible to periodontal disease and that small amounts of plaque may be more than the attached tissue can tolerate.


Uterine contractility and plasma levels of steroid hormones after intravaginal treatment of pregnant Japanese monkeys (Macaca fuscata fuscata) with 16,16-dimethyl-trans-delta2-prostaglandin E-1 methyl ester. Intravaginal treatment with a PGE-1 analogue (ONO-802) resulted in strong uterine contractions with a high frequency which lasted for more than 3 h. When 20-50 microgram ONO-802/kg were administered intravaginally 5 times every 3 h in 5 pregnant animals, vaginal bleeding started by 6 h and abortion occurred by 26 h after the initial treatment. There were no significant side effects. Plasma levels of steroid hormones, especially progesterone and 20alpha-dihydroprogesterone, fluctuated initially and then finally dropped to undetectable levels within 24 h.


Reproductive capacity of rhesus monkeys following bilateral ovarian x-irradiation. The effect of ovarian X-irradiation of the rhesus monkey upon menstrual cycle length, duration of menstrual bleeding, excretion of gonadotrophin in the urine, concentration of gonadotrophin in the pituitary gland, ovarian histology, and breeding performance was investigated. Doses below 4000 R had no significant effect upon the above criteria. By contrast, doses of 4000 to 7000 R rapidly induced amenorrhoea in most animals, but unexpectedly these animals did not excrete greater than normal amounts of gonadotrophin. The pituitary content of gonadotrophin in cyclic and non-cyclic animals was not significantly different. Some births occurred in the animals which had been X-irradiated.


Acute microwave irradiation and cataract formation in rabbits and monkeys. Rabbits and monkeys were irradiated in the near field of a cavity-backed 2450 MHz resonant slot radiator, to determine the cataractogenic threshold. Rabbits developed cataracts at incident "apparent" power densities of 180 mW/cm2 (E2/120 pi, where E=rms/electric field strength). Monkeys sustained facial burns, but no lens damage, even at incident "apparent" power densities of 500 mW/cm2. These results were substantiated by computer thermal models.


Histocompatibility (HLA) antigens in heterotopic ossification associated with neurological injury. Twenty patients with heterotopic ossification were HLA typed. The group consisted of 12 patients with severe cranio-cerebral injury and 8 with spinal cord injury. No significant differences in the frequency of any HLA antigens were found in these patients when compared to 631 healthy matched controls. None of the patients was B27 positive.


Hypercalciuresis in trauma patients on high-nitrogen enteral and parenteral diets. Calcium balances in ten enterally or parenterally hyperalimented trauma victims were compared as protein intake was manipulated from 50.5 +/- 12.8 to 128.0 +/- 17.4 gm/day during an isocaloric metabolic balance study. Calciuresis increased as protein intake increased in all subjects, resulting in an average reduction in daily calcium balance of 195 +/- 65 mg/day (p less than 0.001). There was no difference in fecal calcium in the enterally fed subgroup. Total and "corrected" total serum calcium were lowered, and indirect evidence suggests that ionized calcium was lowered as well. The mechanism of the increase in urinary calcium is not fully elucidated, although it appears to be a direct effect on the kidney rather than an indirect influence of calcium homeostasis. It is suggested that a calorie/nitrogen ratio of about 360 be maintained in enteral and parenteral alimentation of trauma victims. Thus nitrogen balance can be maintained by the increased nonprotein calorie availability, and possible complications of increased calcium mobilization and excretion can be avoided.


The lateral ankle sprain: an experimental study. An experimental study in 39 ankles of the mechanisms of lateral ankle sprains was carried out using a simple qualitative apparatus. The mechanisms studied were: 1) supination-inversion, which was divided into ankle in plantar flexion and ankle in neutral position, since the orientation and tension of the ankle capsule and ligaments are related to the ankle position; 2) supination-internal rotation; and 3) supination-plantar flexion. Fresh amputation specimens were used. It was concluded that complete rupture of the anterior fibulotalar ligament is always the first lesion to occur in the lateral ankle sprain except when a supination force is applied to the ankle in neutral position when an incomplete tear of the fibulocalcaneal ligament may precede the total rupture of the anterior fibulotalar ligament. A partial rupture of the anterior deep fibers of the deltoid ligament can occur in extreme degrees of internal rotation or plantar flexion. A four-part grading system is suggested.


Giant urethral diverticulum after free full thickness skin graft urethroplasty. A case of a giant urethral diverticulum, developing as a complication of a free skin graft urethroplasty 2 years previously, is reported. The incidence of diverticulum formation in reported series of free skin graft urethroplasty is small. The degree of dilatation present in this case has not been reported in the recent literature and its management is discussed.


Plasma cell dyscrasia. Analysis of 423 patients. Present clinical and laboratory diagnostic criteria permit a more accurate diagnosis and closer follow-up of patients with plasma cell dyscrasias. A ten-year follow-up of a group of 423 patients showed that the indications for and the adjustment of treatment are more precise when these criteria are summarized into profiles based on each diagnostic category. M components may be an indication of the presence of another sometimes nonreticular malignant neoplasm. The improvement of the specificity and sensitivity of immunologic methods sheds additional light on mechanisms controlling the synthesis of homogeneous antibodies such as prevalence of IgM-K in mixed cryoglobulinemia and lambda-light chains in IgD myeloma, excretion of lambda-Bence Jones proteins in amyloidosis, and greater IgG-subclass restriction in multiple myeloma as compared with benign monoclonal gammopathy. The activation of additional clones (biclonal gammopathies) was found in 3% of our patients.


Congenital hypothyroidism control programs. A cost-benefit analysis. Comprehensive screening programs to control congenital hypothyroidism (CH), a preventable form of mental retardation, are being considered by some public health agencies. The proposed programs would test neonates' blood for thyroxine and, if warranted, provide follow-up testing and therapy. The estimated cost of detecting a single case of CH is $9,300, which includes specimen collection, laboratory analysis, and retesting of border-line cases. The present value of the treatment costs of CH adds $2,500 per case, a total cost of $11,800 per case detected and child treated. The economic benefits (averted costs of institutionalization and special education and increased productivity of the affected person) are estimated to have a present value of $105,000 per case, yielding a cost-benefit ratio of 1:8.9.


Hypokalemic rhabdomyolysis and acute renal failure. Occurrence following total parenteral nutrition. A patient experienced severe hypokalemia in the setting of prolonged nasogastric suction and total parenteral nutrition. Severe rhabdomyolysis and acute renal failure ensued. Review of the literature failed to disclose a similar case of hypokalemic rhabdomyolysis and acute renal failure, although the syndrome has been associated with other causes of hypokalemia, and its pathophysiology has been investigated in experimental models. The morbidity associated with extensive myonecrosis and severe, acute renal failure in this patient indicates that hypokalemia and other electrolyte abnormalities should be aggressively corrected in similar clinical settings.


Liver function values in adults receiving total parenteral nutrition. A retrospective review was made of results of conventional liver function tests in adult patients who received fat-free total parenteral nutrition (TPN) for two weeks or longer and who did not have other obvious causes for liver function abnormalities. A "meaningful" increase (greater than or equal 50% increase above baseline pre-TPN value) in SGOT levels was noted in 68% of patients, in alkaline phosphatase levels in 54%, and in serum bilirubin levels in 21% of patients. The median peak values for SGOT, alkaline phosphatase, and bilirubin were 3-, 1.9-, and 0.25-fold above the upper limit of normal, respectively. The median time interval of peak increase for each of the three tests was between 9 and 12 days after TPN was started. Liver biopsy specimens from four patients, taken when liver function values were abnormal, showed pronounced steatosis in three patients and mild periportal cholestasis in the fourth patient. The cause(s) of the elevated liver values is unknown, but possibilities include cellular damage, such as steatosis, and an "overshoot" of enzymes when starved patients are refed.


[Fundamental studies and clinical evaluation of PC-904 in urinary tract infection (author's transl)]. Measurement of MICs of PC-904, CBPC and GM against 135 strains of Pseudomonas aeruginosa isolated from patients with urinary tract infections was performed. Susceptibility to PC-904 of Pseudomonas aeruginosa was found to be 3 approximately 7 times more sensitive than that to CBPC and as same as that to GM with inoculum size of 10(8)/ml and 10(6)/ml. Serum level of PC-904 reached a peak of 38.5 microgram/ml 15 minutes after 0.5 g intravenous administration. Urinary recovery rate unit 6 hours after the administration was 12.5%. Overall clinical efficacy of 6 cases of acute simple cystitis and 3 cases of chronic complicated cystitis was judged to be 83.3% and 33.3% respectively by a criterion proposed by the UTI Committee in Japan.


Comparative vasodilator effects of nitroprusside, phentolamine, and nitroglycerin on hemodynamics, regional myocardial function and epicardial electrogram in dogs with acute myocardial ischemia. The effects of nitroprusside (NP), phentolamine (PH), and nitroglycerin (NTG) were studied on systemic hemodynamics, regional contraction and epicardial ST segment in the border and non-ischemic zones of the left ventricle of anesthetized open chest dogs. The anterior descending coronary artery (LAD) was completely occluded. NP (5 microgram/Kg/min) or PH (100 microgram/Kg/min) was drip-infused, or a bolus injection of NTG (20 microgram/Kg) was administered intravenously. The 3 vasodilator agents produced somewhat similar reductions in systemic arterial pressure. However, NP caused a greater reduction in total peripheral resistance (TPR) than in left ventricular end-diastolic pressure (LVEDP), and caused a decline, in the ischemic marginal zone, in both ST segment eievation and paradoxical systolic lengthening. PH decreased TRP without reducing LVEDP and elevated the ST segment. NTG markedly reduced LVEDP and TPR slightly. NTG improved the elevated ST segment and paradoxical systolic expansion of the segmental myocardium in the border zone. Cardiac output rose with NP and PH, whereas injected NTG caused a reduction in cardiac output. These findings suggest that NP favourably affects the ischemic myocardium mainly by reducing the afterload and that the NTG-induced improvement of myocardial ischemia can be attributed mainly to preload reduction, while PH enhances cardiac function with slight or no improvement of myocardial ischemia in the border zone.


IgE antibody production to exoenzymes and common antigen (OEP) of Pseudomonas aeruginosa in mice. IgE antibody production to exoenzymes and common antigen (OEP) of P. aeruginosa was studied in mice that were injected with the antigens incorporated into water-in-oil-in-water (w/o/w) emulsion or Al(OH)3 gel. OEP and protease toxoid (PT) elicited IgE antibody response but elastase toxoid (ET) did not. Capacity of the OEP to produce IgE antibody was reduced remarkably by it's protease treatment, which suggested that the capacity lies in the protein portion of OEP. The w/o/w emulsion was less effective than Al(OH)3 gel in adjuvanticity to elicit IgE antibody response, but the emulsion enhanced the IgM and/or IgG antibody response to PT and maintained a constant level for a long period. These findings may suggest that IgE antibody response to some components of P. aeruginosa could be induced in man. High serum level of IgE was observed in some cases of cystic fibrosis caused by P. aeruginosa infection, although the IgE antibody activity has not yet been determined.


Passive hemagglutination reaction using formalinized sheep erythrocytes treated with tannic acid and coated with exotoxin of Pseudomonas aeruginosa. Passive hemagglutination (PHA) tests using fixed sheep erythrocytes coated with exotoxin of Pseudomonas aeruginosa were devised for estimating antibodies of the exotoxin. No serological cross-reactivity among exotoxin OEP, protease and elastase of P. aeruginosa was foud by the PHA tests. The exotoxin PHA reaction was more sensitive than the neutralizing reaction of skin necrotizing activity of exotoxin by guinea pigs. Thirteen out of 40 sera of patients with P. aeruginosa infections showed PHA titers from 40 to 1,280, while those of 20 healthy human sera were under 40.


L-forms of Pseudomonas aeruginosa. 3. The serological cross-reactions among stable L-forms of Pseudomonas aeruginosa, L-form of Streptococcus pyogenes and mycoplasmas. The serological cross-reactions among stable L-forms of Pseudomonas aeruginosa, or of Streptococcus pyogenes and mycoplasmas were investigated in passive hemagglutination (PHA) and agar gel diffusion tests. (1) PHA active fraction which reacts most strongly with homologous serum was obtained from the sodium dodecyl sulfate soluble fraction of L-form membrane after disruption by Braun cell homogenizer. (2) Antiserum prepared against L-forms in rabbits showed high-level stimulation of PHA antibodies, while it showed little stimulation of agglutinating antibodies. (3) In PHA and agar gel diffusion tests, antiserum to L-form of P. aeruginosa strain IFO-3,455 reacted with L-form of strain N-10, which is serologically different in serotype from strain IFO-3,455. Furthermore, the two L-forms of P. aeruginosa cross-reacted with a L-form of S. pyogenes. 4) L-forms of P. aeruginosa and S. pyogenes did not react with five strains of mycoplasmas in PHA and agar gel diffusion tests.


Partial characterization of a fetal lung antigen associated with human bronchogenic carcinoma. A human lung tumor-associated fetal antigen (LTFA) has been partially isolated and characterized. The antigen that differs in several immunochemical parameters from previously described lung cancer antigens was shared by fetal lung and liver tissue. The neoantigen migrated in immunoelectrophoresis as an alpha2-beta globulin, had an average molecular size of 7S, and was soluble in 50% saturated ammonium sulfate. Whereas LTFA was insensitive to both DNase and RNase treatment, its antigenicity was completely abolished by pronase. The biologic significance of this antigen and its possible clinical use were discussed.


Estrogenic properties of 3,9-dihydroxy-7,12-dimethylbenz[a]anthracene in rats. Previously, the 3,9-dihydroxy derivative of benz[a]-anthracene was shown to be weakly estrogenic. The availability of the related diol of the mammary carcinogen dimethylbenz[a]-anthracene, i.e., 3,9-dihydroxy-7,12-dimethylbenz[a]anthracene (3,9-diOHDMBA), prompted a similar study of its estrogenic properties. The competitive binding studies of 3,9-diOHDMBA with 17beta-estradiol in the uterine cytosol of immature SD rats gave a Ka of 1.7 x 10(8) M-1. 17beta-Estradiol (10(-9) M) binding to the 8S binding protein was inhibited by 3,9-diOHDMBA at concentrations similar to those of nafoxidine HCl (1 x 10(-5) M). Bioassay demonstrated that the diol possesses 1/4,464 the activity of 17beta-estradiol.


[Variants of hemodynamic changes in acute period of myocardial infarct and the importance of their detection for treatment]. Sixty-three patients suffering from acute myocardial infarction were examined within the first 24 hours of the disease (27 within the first 6 hours) by means of catheterization of the right parts of the heart with a Swan-Ganz balloon catheter and thermodilution. Comparison between the cardiac output and the pressure of left ventricular filling allowed the following hemodynamic variants of myocardial infarction to be distinguished: normo-, hypokinetic, with increased pressure of left ventricular filling and normal cardiac output, hypovolemic, and hyperdynamic. The results of the tests with acute rheopolyglucin load (9 patients) showed that some of the patients with normal values of hemodynamics had latent cardiac insufficiency. Hemodynamic study and recognition of the variant of hemodynamic changes in the acute period of myocardial infarction made it possible to determine properly the indications for the use of vasodilators, active inotropic agents, and infusion therapy.


Influence of exchange volume and dialysate flow rate on solute clearance in peritoneal dialysis. To find the ideal dialysate flow rate and exchange volume for use in long-term peritoneal dialysis, 10 patients were studied over a period of 1.5 yr. Exchange volumes of 1 or 2 liters and dialysate flow rates of 1, 2, 3, 4, and 6 liters/hr were tested. Dextrose concentration remained constant at 1.5 g/100 ml. Peritoneal clearances for BUN, creatinine, and uric acid were calculated at 2, 5, 10, 15, and 20 hr during dialysis making a total of 120 clearances for each patient. All patients used a reverse osmosis automatic machine. The clearance of all three solutes tended to be higher with exchange volumes of 2 liters than they did with 1 liter; this trend was significant for BUN (P less than 0.025) and uric acid (P less than 0.025) but not for creatinine. There was a significant rise in clearance with increasing flow rates per hour for all solutes as shown in the following table. (Formula: see text), Since patients could not tolerate a flow rate of 6 liters/hr, we conclude that flow rate of 4 liters/hr with a 2-liter exchange will give maximum efficiency.


[Oculomotor signs in cerebellar disease shown in ataxia telangiectasia (Louis Bar) (author's transl)]. Disturbances of the eye movements are described in 2 brothers with ataxia telangiectasia (Louis Bar): pathological smooth pursuit and command movements of the eyes (hypometry) with a preseved doll's phenomenon, increased reaction times of voluntary saccades, failure of gaze holding, gaze nystagmus, altered optokinetic nystagmus, and distinct convergence defect. These oculomotor defects are the result of cerebellar lesions. The E.N.G.-findings in pathologically changed pursuit movements are in accordance with those disturbances of eye movements shown by Westheimer and Blair in cerebellectomized monkeys.


[Ocular findings in reno-facial dysplasia (Potter-syndrome) (author's transl)]. The clinical and pathological details of a case of reno-facial dysplasia are presented and described. Hyperplasia and lamination of Bowman's membrane, corneal endothelial dystrophy with degenerative changes in the posterior stroma, hypoplasia of the retinal ganglion cell and nerve fibre layers, and severe changes in the retinal and iris blood vessels are believed to be pathognomonic ocular features of this syndrome, in addition to cataract and signs of immaturity. These findings are compared with the few descriptions of the syndrome previously published. The corneal damage is postulated to result indirectly from oligohydramnios which causes chronic compression of the globes and thus endothelial damage due to contact with the spherical cataracts. The pathological changes in the retinal and iris vessels are either genetically determined or the result of chronic hypoxia.