[Temperature-dependent changes in the profile of the sarcoplasmic reticulum membrane hydrophobic zones].

The dependence of the state of the hydrophobic zone of rabbit sarcoplasmic reticulum (SR) membranes on temperature of the membrane fragment suspension before rapid freezing was studied by the freeze fracturing technique. It was shown that within the temperature range of--15-- +37 degrees C the amount of intramembrane particles and their distribution in the membrane plane and between their convex and concave surfaces do not practically depend on the temperature of the SR membrane suspension. This is indicative of the lack of correlation between the physical state of the phospholipid matrix (gel -- liquid crystal) before freezing and the nature of the profile of the membrane hydrophobic zone revealed after fracturing. The disturbances in the protein -- lipid interactions in the membrane under the effects of mersalyl or aqueous solutions of diethyl ester followed by complete inactivation of Ca2+-dependent ATPase lead to a decrease in the amount of intramembrane particles, which is especially well-pronounced at 37 degrees and -15 degrees C.


Bio-materials science and technology.

Materials in current use resulting from clinical acceptance are reviewed. Requirements for a bio-material are considered and problem areas still awaiting solution are identified. These include fatigue, wear, corrosion and adverse tissue effects. The question of relating the structure of materials to their in-vivo properties and the application of this to development of bio-materials is next considered. The properties of the tissues and the way in which newer materials are better adapted to the dynamic properties of these is discussed and future developments are considered in the light of this.


Phosphofructokinase in human blood cells.

The subunit composition of phosphofructokinase from normal and malignant blood cells has been investigated by means of immunologic, electrophoretic, and chromatographic methods. Immunoprecipitation tests were performed with three specific antisera recognizing each of the basic subunits of human phosphofructokinase: muscle, M-type; liver, L-type; and fibroblast, F-type. Mature polymorphonuclear cells contain mainly L-subunits, while lymphocytes and platelets contain hybrids formed of L and F subunits; these hybrids can be electrophoretically separated. Red cell phosphofructokinase is composed of L and M subunits, as judged by its reactivity with anti-L and anti-M-type antisera. The various M-L hybrids composing red cell phosphofructokinase could be only separated by chromatography on DEAE-Cellulose. Lymphocytes from patients with chronic lymphocytic leukemia and lymphoblasts from patients with acute lymphoblastic leukemia contain phosphofructokinase forms similar to those from normal lymphocytes, while the immature granulocytic cells (leukemic myeloblasts and myeloid cells of chronic myeloid leukemia) are characterized by a reinforcement of enzyme inhibition by anti-F-type antiserum. Lymphoid lines in culture (Epstein-Barr virus (EBV)-induced or malignant lymphoma-derived lines) are characterized by the indistinctive expression of all three basic subunits, similar to that found in some fetal tissues. This article represents the first description of the isozymic nature of phosphofructokinase in platelets and white blood cells and of its changes with malignancy and cell culture. This enzyme might represent a useful marker in the characterization of the leukemic cells.


A study of arterial prostheses by scanning electron microscopy.

Scanning electron micrographs were taken of ten different vascular prostheses. The micrographs showed that some prostheses were damaged and some had traces of chemicals on their surface. The application of standard vascular clamps damaged most grafts and some showed remarkable changes on resterilization.


Serotonergic facilitation of facial motoneuron excitation.

The effect of serotonin (5-HT) on motoneurons located in the facial nucleus of the rat was investigated in the present study. Microiontophoretic application of 10--200 nA pulses of 5-HT lasting from 1 to 10 min failed to excite facial motoneurons. However, small amounts of 5-HT facilitated the subthreshold and threshold excitatory effects of iontophoretically applied glutamate on these cells. Typically, the current of glutamate required to produce an activation of facial motoneurons was reduced by at least 50% in the presence of 5-HT. In addition, 5-HT markedly shifted to the left the cumulative dose-response curve of glutamate-induced excitation of motoneurons. The 5-HT releasing agent p-chloroamphetamine (PCA) facilitated the excitatory effects of glutamate on montoneurons in control animals, but not in those pretreated with the 5-HT also facilitated the subthreshold and threshold excitation of motoneurons produced by stimulation of the motor cortex and the red nucleus. The facilitating effect of 5-HT was blocked by methysergide. Norepinephrine also facilitated facial motoneuron excitation but this effect was not blocked by methysergide. It is concluded that 5-HT in the facial nucleus functions in a manner that is not analagous to direct excitation, but rather acts as a gain setter to enhance the effects of excitatory afferent inputs.


Interaction of sodium with the sarcolemmal calcium system.

Sarcolemma isolated from guinea pig heart binds calcium in an ATP-dependent manner. Sodium ions decrease the total amount of calcium bound by the membranes. ATP-dependent calcium binding is more sensitive to sodium than the non-ATP-dependent calcium binding. The ATPase active during calcium binding is affected by sodium ions to the same extent as the ATP-dependent calcium binding process. The inhibition of the calcium binding process and of ATPase activity by sodium was more pronounced when the membranes were preincubated with sodium. The effect of sodium on calcium binding is dependent on both the time of contact between sodium and the membranes and the concentration of sodium. It is suggested that the effect of sodium on the calcium binding system in the sarcolemma may be a link between the inhibition of Na+K+-ATPase (EC 3.6.1.3) by cardiac glycosides and the subsequent increase in intracellular calcium.


The biosynthesis of the free sterols and sterol esters of Neurospora crassa.

The composition of the free and esterified sterols in Neurospora crassa was examined as a function of incubation time in starvation medium containing [2-14C]mevalonic acid. The 14C incorporation was monitored in nuclear methylated and 4,14-desmethyl sterol fractions. After 7 h incubation, sterol esterification had increased from an initial 5% in the log phase culture to 48% of the total sterol pool, with a concomitant decrease in free sterols. The relationship of the free and esterified sterol components in ergosterol biosynthesis is discussed.


Cardiac output measurement by thermodilution.

The accuracy of thermodilution for measuring cardiac output was studied by comparing this method with measurements obtained by an electromagnetic flowmeter in the dog. Thermal curves were computed by a cardiac output computer and absolute flows were obtained by pump calibration of the flowmeter. Regression analysis showed an excellent correlation (P less than 0.001) between thermodilution measurements with injectates at 0 degrees C and flowmeter measurements using either cannulating probes (n = 105, r = 0.98) or periaortic probes (n = 100, r = 0.96). With the use of normal room temperature injectates, a good correlation was also found with absolute flows (n = 75, r = 0.92, P less than 0.001). Thermodilution overestimated cardiac output by 3% to 9%. In 32 pairs of successive cardiac output determinations by thermodilution, there was no significant difference between the two measurements (P greater than 0.05). In eight patients cardiac output was measured postoperatively by thermodilution with injectates at 0 degrees C and 24 degrees C administered in rapid succession. Regression analysis of 50 pairs of measurements at the two temperatures showed a strong correlation between the two techniques (r = 0.96) and the two results were not significantly different (P = 0.00001).


Guidelines to birth control counselling of the physically handicapped.

Birth control counselling of well motivated physically handicapped men and women is discussed in a series of suggested steps: (1) preappointment arrangements are made to ensure physical access to the office, and the partner or a helper may be invited to the visit; (2) the patient is encouraged to name the desired birth control method; (3) the patient's fertility is established from the history and the results of physical examination and laboratory tests; (4) methods of birth control are matched to the patient's physical and mental capabilities; (5) potential side effects of the proposed methods are considered in the light of the handicap; (6) a method is finally recommended that may be a trade-off, with ease of use balanced against efficacy, and living with side effects balanced against the risks of pregnancy; and (7) rechecks are necessary to ensure that the patient is using the method with skill and satisfaction.


A phase I study of chlorozotocin (NSC 178248).

Chlorozotocin was administered by rapid intravenous infusion to 35 patients with advanced cancer on either single-day of five-consecutive-day schedules. Total doses per course ranged from 12.5 to 200 mg/m2. On either administration schedule, dose limiting toxicities were thrombocytopenia and leukopenia at total doses of 150 mg/m2 to 200 mg/m2. Repetitive courses of drug may produce progressive impairment of renal and bone marrow function. Nausea and vomiting were infrequent and mild without definite relationship to dose. Minor reversible nondose related increases in SGOT and in serum creatinine occurred at all doses on both schedules. The plasma half-life of intact N-nitroso groups averaged 9.5 minutes after rapid intravenous administration of doses up to 40 mg/m2 and 12.5 minutes after doses of 150 or 200 mg/m2. No differences between plasma half-lives were seen between identical doses given on the first and fifth days of the five-day schedule. Objective tumor regression was noted in one patient with bronchogenic large cell carcinoma and one patient with metastatic melanoma.


Cultured human leukemic non-T/non-B lymphoblasts and their stimulating capacity in "one-way" mixed lymphocyte reaction: suggestive evidence for early T-cell or B-cell precursors.

It is now well recognized that a large proportion of cases with acute lymphoblastic leukemia are classified as non-T/non-B neoplastic disease. The origin of leukemic non-T/non-B cells is at present not known. It has been shown that fresh or cultured leukemic T lymphoblasts exert no stimulating capacity while leukemic B lymphoblasts exert a strong stimulation in "one-way" mixed lymphocyte reaction. It has also been shown that fresh leukemic cells from some patients with non-T/non-B acute lymphoblastic leukemia possess a strong stimulation while leukemic cells from other patients with this disease possess no stimulation on allogeneic lymphocytes. The present study shows that cultured leukemic lymphoblasts from 3 non-T/non-B cell lines (NALL-1, NALM-6 and NALM-16) consistently exert a strong stimulation on allogeneic lymphocytes. On the other hand, cultured leukemic lymphoblasts from 2 non-T/non-B cell lines (REH and KM-3) consistently fail to stimulate in "one-way" mixed lymphocyte reaction. Our data clearly support the speculation that leukemic non-T/non-B cells which possess the stimulating capacity may represent less differentiated leukemic B lymphoid cells (pre-B cells) and leukemic non-T/non-B cells which possess no stimulating capacity may represent less differentiated leukemic T lymphoid cells (per-T cells).


Histochemical and ultrastructural properties of myoid cells in the thymus of the frog.

Histochemical and ultrastructural properties of myoid cells in the thymus of the frog were investigated and compared with properties of skeletal muscle fibres. The histochemical reactions of phospholipids, phosphorylase, succinic dehydrogenase and adenosine triphosphatase activities in myoid cells were characterized by considerable variability. Individual myoid cells apparently possess different enzyme activities which correspond to different stages of development, maturity and degeneration of these cells. The mature mononucleated myoid cells have similar enzymatic properties to the fast muscle fibres of the frog. This finding has been extended by ultrastructural observations. Features, typical of fast muscle fibres of the frog, e.g. the presence of the M-line, straight and narrow Z-line and well developed triads were found in the majority of mature myoid cells.


Split gene for mitochondrial 24S ribosomal RNA of Neurospora crassa.

The 60 kb circular mitochondrial genome of N. crassa has previously been shown to contain a single transcription unit for 17S and 24S rRNA mapping within the largest Eco RI fragment E1 (19.6 kb). This fragment was isolated from uncloned mitochondrial DNA and further analyzed by cleavage with restriction endonucleases Hind II, Hind III, Bam HI, Pvu II and BgI I, and by electron microscopy of rRNA/DNA hybrids. The resulting map shows a 2.3 kb intervening sequence interrupting the gene for 24S rRNA. The main part (2.7 kb) of this gene is separated from the 17S rRNA gene by a 5 kb segment which contains several transfer RNA genes. This segment is much longer than the putative 1 kb spacer sequence within the 32S precursor molecule for both rRNAs, suggesting a second splicing event in that region.


Diphenhydramine protection of the failing myocardium during gram-negative endotoxemia.

Gram-negative endotoxin (Escherichia coli, 4 mg/kg) was found to produce a sustained fall in systemic arterial pressure, left ventricular pressure, and cardiac output that could be blocked by the histamine antagonist diphenhydramine. Histamine infusion was found to produce a parallel depression of systemic arterial pressure. Further, endotoxemia was found to produce a significant depression of myocardial contractility (dP/dt max) that could also be blocked by diphenhydramine. Cardiac myofibrillar adenosine triphosphatase (ATPase) activity from endotoxin-shocked hearts was found to be depressed, ATPase activity from subendocardial myofibrils being more depressed than that from subepicardial myofibrils. Myofibrillar ATPase activity was significantly protected by pretreating the animals with diphenhydramine. It is concluded that the initial hemodynamic phase of endotoxin shock is histamine-mediated and that this hemodynamic depression can be blocked with diphenhydramine. Further, it appears that endotoxin is capable of depressing myocardial contractility by depressing contractile protein function (myofibrillar ATPase activity)--the subendocardial surface more so than the subepicardial surface--and this depression of myocardial contractility can be blocked with diphenhydramine.


The influence of left ventricular late diastolic filling on the A wave of the left ventricular pressure trace.

To study the influence of left ventricular (LV) late diastolic filling on the A wave of the LV pressure, simultaneously recorded echocardiographic LV dimensions and high-fidelity LV pressure measurements were taken in 24 patients. Group 1 comprised eight patients without LV hypertrophy (LVH) and LV end-diastolic pressure (LVEDP) less than or equal to 13 mm Hg. Group 2 comprised 16 patients with LVH secondary to aortic stenosis, idiopathic hypertrophic subaortic stenosis, or hypertension and increased LVEDP. Patients in group 2 had significantly thicker left ventricles, decreased mitral E-to-F slopes, and larger A waves in the LV pressure curve. On the basis of end-diastolic chamber stiffness, we divided group 2 into two populations: 12 patients (group 2A) with end-diastolic chamber stiffness similar to that in group 1, and four patients (group 2B) with markedly elevated end-diastolic chamber stiffness. Patients in group 2A had a larger atrial contribution to LV filling than those with markedly abnormal stiffness (group 2B). Therefore, in LVH an increased A wave in the LV pressure may be related to either elevated end-diastolic chamber stiffness or augmented left atrial volume transport.


Exercise-induced ST elevation in patients without myocardial infarction.

A review of 6040 consecutive exercise tests yielded 106 patients without previous myocardial infarction (MI) who had exercise-induced ST elevation (greater than or equal to 0.5 mm in a 15-lead ECG system). In 46, ST elevation was correlated with left ventriculography and coronary angiography. Coronary artery disease (CAD) (greater than or equal to 70% narrowing) was detected in 40 of 46 patients: 12 patients had one-vessel disease, 13 had two-vessel disease, and 15 had three-vessel disease. Resting ventriculograms were normal in 36 of 40 patients. Of 21 patients with anterior (V1-V3) ST elevation, 86% had a left anterior descending (LAD) obstruction and 78% had obstruction proximal to the first diagonal branch. LAD disease occurred significantly more frequently than right and circumflex CAD. There was no anatomic correlation of three persons with lateral (leads V4--6, I or aVL) or 27 patients with inferior-posterior (leads II, III, aVF, Y or Z) exercise-induced ST elevation. Therefore, exercise-induced ST elevation is strongly correlated with CAD but not resting wall motion abnormalities. Further, anterior exercise-induced ST elevation in patients without a previous MI often predicts a significant proximal LAD obstruction.


Noninvasive screening criteria for enhanced 4-year survival after aortocoronary bypass surgery.

Two thousand one men with coronary heart disease (CHD) who were enrolled in the Exercise Testing Registry of the Seattle Heart Watch had symptom-limited maximal exercise tests at the initial clinical examination and follow-up surveillance of subsequent mortality for 4.1  +/- 1.6 years. When subdivided into three mutually exclusive subgroups, 636 patients did not have exertional myocardial ischemia, left ventricular dysfunction or cardiomegaly; 885 without cardiomegaly had only exertional ischemia; 480 had left ventricular dysfunction by either cardiomegaly and/or two noninvasive exertional criteria, with or without exertional myocardial ischemia. Three hundred thirty-one men had aortocoronary bypass surgery, while 1670 remained unopened for at least 4 years. Only 34% of the operated patients who had left ventricular dysfunction, as defined, showed a marked improvement in 4-year survival rates (p less than 0.01). Differences in the annual CHD mortality rates in relation to surgical treatment in the other two groups were not statistically significant. Restricting the analysis to a subset of patients who had invasive studies did not alter the conclusion. Accordingly, we suggest the use of noninvasive criteria to aid preliminary screening of patients for invasive studies and surgical treatment.


A parental perspective on the Honeylands Home Visiting Project for severely handicapped infants provided by three mothers of older handicapped children.

Three mothers of severely handicapped children, who had not attended Honeylands nor received any home visiting, were asked to attend and participate in the monthly group meetings for the second year of the three year project (Rayner 1978). They each then decided to visit a family with their home therapist. They comment on the responsibility undertaken by all parties to this work; parents, therapist and supportive team.


A study of erythrocyte fatty acids, adenosinetriphosphatase and acetylcholinesterase in cystic fibrosis.

1. The proportions of both saturated and polyunsaturated fatty acids were measured in the erythrocytes in Cystic Fibrosis (CF) patients along with two membrane bound enzymes ATPase and acetylcholinesterase. Linoleic acid was found to be significantly decreased and arachidonic acid increased in CF patients. The proportion of saturated fatty acids were not significantly different from the controls. Only adenosinetriphosphatase activity was found to be reduced and not acetylcholinesterase in CF patients.


Self indentified personality patterns of children with facial or orthopedic disfigurement.

This study compared personality characteristics of children with cleft lip and palate to another group of children with different observable physical impairment (orthopedic disability) and speech difficulties. It was hypothesized that different types of observable physical stigmata may result in different personality adaptations. Forty-five children from each of two groups (25 males and 20 females) were matched for sex, age, and intelligence. They were compared using the Missouri Children's Picture Series, a non-verbal personality test, on the following dimensions: Conformity, Masculinity/Femininity, Maturity, Agression, Inhibition, Activity Level Sleep Disturbance and Somatization. The results indicate that males with cleft lip and palate are significantly higher on Maturity and Inhibition while Orthopedically Disabled males are higher on Agression, Activity Level, and Somatization. Cleft lip and palate females are significantly higher on Maturity and Inhibition while Orthopedically Disabled females are higher on Masculinity. The results indicate differential personality adaptations in the two different types of observable physical impairments. Results are discussed in terms of their relationship to selected psychosocial variables.


Allergic contact dermatitis to isopropylaminodiphenylamine (IPPD).

Fifty-one patients allergic to IPPD have been reviewed and the clinical features and prognosis discussed. In 38 of the 51 patients, the dermatitis was considered as occupational, the majority being employed in the transport industry.


Cyanoacrylate dermatitis.

An outbreak of irritant dermatitis from a cyanoacrylate glue among a group of electronic assembly workers is described. It was caused by vaporization of monomer under conditions of low relative humidity. No further outbreak occurred when the humidity of the working environment was raised above 55%.


Delayed irritation: hexanediol diacrylate and butanediol diacrylate.

Ephemeral topical contact with hexanediol diacrylate and butanediol diacrylate may cause delayed irritant dermatitis. During 4 years' observation of 20 workers utilizing these substances in the electron beam coating department of a door factory, contact sensitization did not occur. The characteristics of delayed contact irritancy are enumerated. The disease must be distinguished from allergic contact dermatitis, acute irritant dermatitis and cumulative irritant dermatitis.


Synergism of vitamins A and E with dermatologic applications.

A synergism between vitamins A and E has been demonstrated by a number of investigators, notably Stanley R. Ames, who showed that in rats on a vitamin E deficient diet, the serum vitamin A level remained low, no matter how much vitamin A was given by mouth, or even by injection, but that adding vitamin E to the diet restored the vitamin A serum level to normal. We have utilized these observations with a high degree of success where vitamin A alone had failed to control three dermatologic conditions involving a defect in keratinization, namely, keratosis follicularis (Darier's disease), pityriasis rubra pilaris, and acne vulgaris. It is possible that a number of additional dermatoses characterized by dyskeratosis or hyperkeratosis might also be benefited by this combination.


Evaluation of abrasives in acne therapy.

Various abrasive materials, such as pumice, polyethylene, and aluminum oxide are widely used as adjuncts in the therapy of acne. The apparent rationale is that abrasion should unseat comedones and deter their formation. We assessed the efficacy of various abrasives and abradant pads. Varying degrees of peeling and erythema were produced, but there was no appreciable reduction of comedones. Aggravation was noted in some cases. Generally, the resorption of papules and pustules was enhanced.


Co-existing aortic stenosis and secondary hypertrophic cardiomyopathy manifested by an hourglass left ventricle. Successful treatment with verapamil.

A patient with moderate aortic stenosis had severe hypertrophy and a typical hourglass appearance of the left ventricle. His effort-induced angina and dyspnea responded to treatment with verapamil. We suggest that the aortic stenosis resulted in secondary hypertrophic cardiomyopathy which may be treated by calcium antagonists.


Radiopharmaceutical bone scanning in pediatric neurosurgery.

Radionuclide bone scanning is an extremely sensitive, safe and widely applicable investigative aid. In most circumstances it cannot be employed to the exclusion of plain radiography as the two procedures--one dynamic and the other static--complement each other. In children, bone imaging demonstrates physiologic characteristics of bone growth and early suture closure, delineates obscure tumors and infection, recent or old trauma not always visible on orthodox radiography and may solve the diagnostic dilemma of a child with heretofore undiagnosed head, neck or back pain.


[Subendocardial jeopardy of the hypertrophied myocardium].

In moderate hypertrophy (+35%) of the canine left ventricle (LV), resting myocardial blood flow (MBF, tracer microspheres) was not significantly altered when compared with controls. The endo/epi flow ratio of the LV was, however, significantly smaller (0.82-0.9) than in controls (1.02-1.17). After coronary dilatation with dipyridamole, coronary flow reserve was smaller in hypertrophied hearts. This became particularly obvious when acute coronary constriction (70%) was induced. There was, however, no indication that after coronary constriction in early hypertrophy the subendocardium was more jeopardized than in controls.


[Role of LD-antigens in allogenic swine liver transplantation].

The different distribution of SD and LD antigens in the liver after a pig liver allograft creates a state of anti-LD immunity. This anti-LD immunity alters the immune response of the recipient and leads to a spontaneous recovery of the liver allograft rejection.


[The contribution of laparoscopy to diagnosis of malignant lymphomas (author's transl)].

Peritoneoscopy revealed in 15 patients with malignant lymphomas splenomegaly (13 patients), hepatomegaly (10 patients, 8 of them with impressive or suspicious alterations of the liver surface) and enlargement of retroperitoneal lymph nodes or localised infiltration of a jejunal loop (3 patients). Aimed biopsy of liver, spleen or lymph nodes frequently established the diagnosis definitively. The various features of malignant lymphomas observable at peritoneoscopy are described. Based on these experiences peritoneoscopy is recommended in suspected malignant lymphomas as a real diagnostic aid.


Monoaminergic control of episodic growth hormone secretion in the rat: effects of reserpine, alpha-methyl-p-tyrosine, p-chlorophenylalanine, and haloperidol.

The effects on GH secretion of reserpine, alpha-methyl-p-tyrosine (alpha-MT), p-chlorophenylalanine (PCPA), and haloperidol were studied in undisturbed, unanesthetized male rats with implanted intraaortic cannulae. The effects of the various drug treatments on motor activity and brain levels of catecholamines (CAs) and 5-hydroxytryptamine (5-HT) as well as the synthesis of the biogenic amines were also studied. Reserpine (10 mg/kg, ip) completely inhibited GH secretion for at least 15 h. Repeated injections of reserpine prolonged this inhibition. Episodic GH secretion reappeared 36 h after the last administration of reserpine, at which time the behavioral inhibition and blepharospasm induced by the drug was less pronounced than after 24 h, but brain levels of CAs and 5-HT were still markedly reduced. Administration of alpha-MT (150 mg/kg; 12, 4, and 2 h before experiments) inhibited episodic GH secretion and caused marked inhibition of motor activity and brain levels of CAs but not 5-HT. The inhibition of episodic GH secretion was more pronounced with haloperidol (0.5 mg/kg; 30 min before experiments) than with alpha-MT but was not as complete as that found 12 h after administration of reserpine. Administration of p-chlorophenylalanine (300 mg/kg; 72, 48, and 24 h before experiments) had no effect on episodic GH secretion, whereas brain levels of 5-HT and 5-HT synthesis were markedly reduced.


Enzymic profiles of bovine pancreatic ductal and acinar tissues.

The plasma membrane enzymes, alkaline phosphatase, bicarbonate-dependent adenosine triphosphatase, 5'-nucleotidase, and carbonate dehydratase, were measured in ductal and acinar preparations of bovine pancreas. Epithelial cells were scraped from the main duct and a piece of acinar tissue was dissected from the whole pancreas for homogenization. All enzymes studied demonstrated higher levels in the duct per milligram protein than in the acinus: bicarbonate-dependent adenosine triphosphatase was 2.8 times higher; 5'-nucleotidase, 4.1 times higher; carbonate dehydratase, 16.9 times higher, while alkaline phosphatase showed only a slight increase in the duct compared to acini.


Effects of phospholipase A2 and albumin on the calcium-dependent ATPase and the lipid composition of sarcoplasmic membranes.

1. The calcium-dependent ATPase activity of phospholipase-A2-digested sarcoplasmic vesicles decreases concomitantly with the contents of residual lysophospholipids and fatty acids when increasing albumin concentrations are applied. 2. Delipidated albumin preferentially removes unsaturated fatty acids and lysophosphatidylcholine. A complete removal of the phospholipids by albumin does not occur. 3. The membrane-bound lysophospholipids were analysed with respect to type of phospholipid, plasmalogen content and fatty acid chains by means of thin-layer chromatography and gas chromatography. 4. While the fatty acid composition of the lysophospholipids is independent of the degree of delipidation, the composition of the residual free fatty acids is found to change with the albumin concentration. 5. Reactivation of the Ca2+-ATPase by oleate leads to reasonable activities at room temperature as long as a minimum of about 30 lysophospholipid molec-les per ATPase is left. The course of the residual Ca2+-ATPase activity with the degree of delipidation is related to the presence of unsaturated fatty acids. 6. No specific role of either sphingomyelin or the plasmalogens has been found.


Bronchodilator activity of dimaprit in the guinea pig in vitro and in vivo.

The bronchodilator activity of the H2-recptor agonist, dimaprit, was assessed in vitro and in vivo. In vitro dimaprit relaxed guinea pig tracheal spirals and parenchymal strips that were constricted by the H1 receptor agonist, 2-PEA, or by carbachol. The H2-receptor antagonist, metiamide, inhibited this effect of dimaprit in vitro on both tissues constricted by 2-PEA but not on the carbachol constricted tracheal spiral. Intravenous infusion of dimaprit in the intact guinea pig resulted in reversal of bronchoconstriction induced by subcutaneous injection of 2-PEA. In vivo pretreatment with the H2-recptor antagonist, metiamide, resulted in a diminished sensitivity to the bronchodilating effects of intravenous dimaprit.


Some effects of an intrauterine device on glucosaminoglycans of the hamster uterus.

The effect of an intrauterine device (IUD) on non-heparin sulfomucopolysaccharide (SMP) was studied in castrated, hormone-treated, and cycling hamsters by photographic densitometry of tissue sections stained specifically for SMP with Alcian blue. Non-heparin SMP increased slightly in the myometrium of IUD-containing uteri of all castrated groups, with the increase being significant in only the peanut oil-treated group. The endometrium also showed slight increases in sulfomucin in IUD-containing uteri of peanut oil, progesterone, and estrogen plus progesterone-treated animals. These increases, however, were not statistically significant. In cycling hamsters the IUD had little effect on uterine non-heparin SMP in most cycle stages.


Early assessment of a tubal plastic (Bleier) clip.

Fifty patients have been sterilized laparoscopically using a plastic tubal (Bleier) clip having a "snap-shut" mechanism. Initial assessment indicates that the method is simple in principle but there are limitations, including the bulky dimensions of the applicator, absence of a safety-catch mechanism, and faults in the clip design. Modifications are indicated before further evaluation.


[Effect of noradrenaline on ion and water transport through frog gall bladder epithelium].

In experiments on isolated gallbladders (GB) of frogs it was established that noradrenaline in concentration of 6.10(-9)--3.10(-4) M acting on the organ from the serosalsurface causes firstly a short increase and then -- a prolonged inhibition of the absorption rate of NaCl -- isotonic fluid from the gall bladder cavity. While the concentration of the mediator increases in the inculation medium, its inhibiting effect increases too. Depression, and at high concentration in the medium, full inhibition of the process of fluid absorption is accompanied with distinct decrease of Na--, K--ATPase activity of gall bladder epithelial cells. Mediator in concentration of 3.10(-8) M caused an increase of membrane potential of the epithelial cells, while its increasing in the inculation medium to 3.10(-6) M caused a decrease of the transmembrane potential difference. Under the noradrenaline influence the increase of the osmotic permeability of the gall bladder's wall for the water flow directed from the mucosa to the serosalsurface of the organ took place, and also the decrease of the wall's permeability for the water flow in the opposite direction was seen. It was concluded that the noradrenaline inhibitory action on the process of absorption of NaCl--isotonic fluid from the gall bladder cavity was observed because of the decrease of the Na--K--ATPase activity, and also because of the change of the permeability of epithelium for the passive ion and water transport.


[Spontaneous discharges of muscle receptors of different functional types].

Characteristics of discharges as well as presence or absence of spontaneous impulse activity (SIA) were studied in 473 receptors of deafferented muscles in anesthetized cats. The SIA was absent in majority of Golgi's organs, pressor receptors, and in elementary dynamic and static receptors of muscle spindles. The SIA probability is particularly high in spindle receptors of phasic-tonic type. Absence or presence of the SIA is one of criteria for identifying the type of receptors. Among the universal receptors of dynamic and position types, the SIA probability increases along with enhancement of the static response. The soleus muscle possesses a lesser amount of units with SIA than the m. triceps. Absence or presence of the SIA seem to depend on different ways of connection between sensitive terminals and the intrafusal fibers of the spindles which have been initially stretched in a relaxed muscle.


Lymph node activation by a factor released from lymphocytes of normal mice in reaction with Mycobacterium kansasii.

Substances which have the same properties as the previously described lymph node activating factor are released from the 4-h culture of 10 X 10(6) lymph node cells from normal non-sensitized mice and 2.5--5 X 10(6) Mycobacterium kansasii cells. They increase the number of lymphocytes with nucleoli synthesizing ribonucleic acid in the popliteal lymph nodes of intact mice and give the precipitation lines with the beta- to alpha-globulin electrophoretic mobility, which are specific for the lymph node activating factor, in reaction with serum against the supernatants from mixed lymphocyte cultures. The conclusion drawn from these observations is that the release of the factor or related substances is one of the more general manifestations of the early response of lymphocytes to foreign cells. The activating and in immunoelectrophoresis specifically reacting substance is not released from lymphocytes of mice from a specific pathogen-free colony. We assume that the release of the factor is not the primary reaction of the non-sensitized lymphocytes but the secondary reaction of lymphocytes presensitized with substances which share antigenic determinants with Mycobacteria.


Gold salt-induced cholestasis.

The authors report the case of a patient with transient intrahepatic cholestasis following the administration of a soluble gold salt, sodium aurothiopropanol sulfonate. Other manifestations of intolerance to gold salts included exfoliative dermatitis and eosinophilia.


Prevention of diabetic glomerulopathy in streptozotocin diabetic rats by insulin treatment.

Glomerular basement membrane thickness (GBMT) has been measured in streptozotocin diabetic rats treated with insulin. The study included 3 groups of 8 rats each: 1) a 'well-controlled' group of diabetic rats under insulin treatment with a plasma glucose level reasonable close to normal values, 2) a 'poorly-controlled' group also under insulin treatment with constant high plasma glucose values, and 3) an age and weight matched non-diabetic control group. After 6 months of diabetes, GBMT was measured applying an intercept method on 3 glomerular cross sections from each of the 24 animals. The measurements showed that mean GBMT was 132.2. nm in the non-diabetic control rats and 131.6 nm in the 'well-controlled' diabetic rats. In the 'poorly-controlled' group the man GBMT was 140.4 nm, i.e. statistically significant increased when compared to each of the two other groups, 2p = 0.022 and 0.012 respectively. The results demonstrate that good blood glucose control in rats preserves normal GBMT.


[Atrioventricular canal associated with Fallot's tetralogy. Anatomo-clinical study of 2 cases].

The Authors are examing two cases of A-V canal associated with T. of Fallot. The most important clinical aspects of this rare cardiopathy result in the following: -- the frequent coexistence with Down dyndrome; -- the ECG and VCG aspects of counterclockwise rotation of the initial vectors of QRS in the frontal plane; -- the simultaneous observation of the typical echocardiographical aspects of both kinds of cardiopathy. The injection of dye into both ventricles allows the precise diagnosis. The post-mortem study in both cases shows the morphology of A-V canal associated with the one of T. of Fallot. From the surgical point of view it is important to take into account the abnormal morphology and extension of VSD. The importance of the part that the conal cushion plays in the morphogenesis of the malformation is discussed.


[Laparoscopic sterilization with electrocautery: complications and reliability (author's transl)].

1084 laparoscopic sterilizations were evaluated in a retrospective study at the Universitäts-Frauenklinik Zürich. The operative and early postoperative complications and the reliability of the method were analysed and compared to the results in the literature. Based on a cumulative statistical analysis 0,5% intraoperative complications required laparotomy, the main indications being haemorrhages and bowel injuries. Failed attempts were encountered in one of 150 patients, the main causes of which were adhaesions and difficulties at establishing pneumoperitoneum. The failure rate of the laparoscopic electrocoagulation of the fallopian tube after a long-term follow-up was about 0,5%, 20--25% of these were ectopic pregnancies. The transection of the fallopian tubes did not diminish the pregnancy rate, but the risk of bleeding was considerably higher with this technic. Concurrently performed therapeutic abortion or preceeeding laparotomy did not increase the operative complication rate.


[Population genetics of the population of the northern European RSFSR. III. Demographic and genetic characteristics of two rural communities of the Pinezhskii District of the Arkhangel'sk Region].

The paper deals with the distribution of genetic markers (systems ABO, Rh, Hp, PTC) and a number of phenotyping traits (folding of arms, hand clasping, tongue rolling, right- and left-handedness, the type of ear lobe, the types of dermatoglyphics patterns) in the inhabitants of 5 villages in the Pinezhsky district of the Arkhangelsky region of the RSFSR. The data presented in this work were obtained in the course of examination of over 900 persons. Among the systems analysed there was a statistically significant deviation from Hardy-Weinberg's equlibrium. It took place in two the least villages. In one case--for ABO blood groups, in another--for Hp system. There are an interesting fact of the excess of heterozygotes 2-1 and some excess of the group 0. Statistically significant differences between villages were shown for four genetic systems. Data on migrations, distribution of gene frequencies and estimated genetic and phenotype distances between villages of the same village community and between two communities suggest, that each village community can be considered as separate subdivided population. Considering the uniformity of the environmental pressure in the region examined, the heterogeneity of the population studied is apparently associated with a random genetic drift.


[Cerebral degeneration in Down's syndrome].

Clinical and neuropathological findings of a 63-year-old male and a 25-year-old female with Down's syndrome are presented. Neuropathological examination of the older patient revealed intense features of Alzheimer's disease or senile dementia, including congophilic angiopathy and extensive mineral deposits in the globus pallidus and in the white matter of the cerebellum. In the hippocampus of the younger patient, plaque-like bodies and a few neurofibrillary tangles were found. From a survey of the cases hitherto reported in the literature it appears that among patients over 50 years of age it is common to encounter pathological features typical of Alzheimer's disease or senile dementia, that plaque-like bodies may occur in the second decade, neurofibrillary tangles in the third decade and a congophilic angiopathy in the fourth decade. The congophilic angiopathy is a frequent finding. Due to their high frequency, calcium or calciumlike deposits are regarded as important histopathological substrates of Down's syndrome. The clinical symptomatology of the long-surviving patients with Down's syndrome is that of a non-characteristic brain aging process and differs from that of the typical Alzheimer's disease. Organic dementia is not regularly found. Altogether, the anatomical findings in adult patients with Down's syndrome indicate a premature aging of the brain, which becomes more significant and widespread with increasing age.


[Lymphangitis carcinomatosa of the lung in carcinoma of the prostate: frequency, radiological appearances and clinical significance (author's transl)].

Lung metastases from carcinoma of the prostate usually manifest themselves as radiologically diffuse lymphangitis carcinomatosa. Unlike the pathological findings, a radiological diagnosis is relatively uncommon. We have investigated this retrospectively in 230 patients; in 192, radiographs were available for study. In over 10% lung metastases were found, mostly in the form of lymphangitis carcinomatosa. In view of the bad prognostic significance and therapeutic implications of lymphangitis carcinomatosa, it is important to bear this in mind and to look for it radiologically.


[Computer tomographic demonstration of lymph node metastases from malignant testicular tumours. A comparison of lymphography and computer tomography (author's transl)].

Lymphography and computer tomography was performed on 64 patients with malignant testicular tumours in order to demonstrate lymph node metastases. In 60 patients it was possible to confirm the findings by surgery. In 43 patients there was agreement between the findings of the computer tomogram and the lymphogram. In 39 of these patients lymph node metastases had been demonstrated, in three there was a false negative and in one a false positive. Amongst the patients in whom there was a descrepancy between the two types of examination, the CT findings were confirmed histologically in twelve, and the lymphographic findings in nine. In 12.5% CT added significant additional information. Accuracy of lymphography was 73% and of computer tomography 80%. Specificity for each examination was 79%.


[Chondromalacia patellae--arthrographic observations on the genesis and diagnosis of cartilaginous damage (author's transl)].

Thanks to recent advances in arthrography, diagnosis of cartilaginous lesions has increasingly become a task of the radiologist. An accurate assessment of the cartilage of the femoropatellar joint can be established via double-contrast technique and so-called "défilé" projections, whereas the axial projection of the patella without contrast medium shows only secondary arthrotic changes of bone and is unsuitable for demonstrating early cartilaginous damage. The classification of dysplastic patellae into different types according to Wiberg and Baumgartl yields a statistical correlation with the frequency of chondromalacia, but does not give any conclusive evidence in individual cases. A special influence on joint mechanics and the development of chondromalacia patellae is exercised by a cartilaginous ridge of the medial patellar facette.


[Paget's disease--manifestations in the vertebral colum. Computer tomographic investigations (author's transl)].

Computer tomography has been found to be of value in the study of deformities and narrowing of the spinal canal in 52 patients with Paget's disease of vertebral bodies. To a limited extent it can also be used for evaluating the intervertebral foramina. Deformities of the spinal canal were classified into three degrees of severity. The most severe changes were found in the lower thoracic region. The presence of neurological complications is an indication for CT studies.


[Computer tomography of the sacroiliac joints (author's transl)].

Computer tomography, like conventional radiography, can demonstrate inflammatory, degenerative or reparative, traumatic and neoplastic lesions of the sacroiliac joints. In some cases computer tomography adds important information, for instance as regards soft tissue changes near the S.I. joints in the presence of neoplastic or posttraumatic lesions (tumour extension, hematoma). Computer tomography is also able to demonstrate minor disalignment of the sacro-iliac joints (so-called sacro-listhesis).


[The kinetics of contrast media in cerebral tumours (author's transl)].

The increase in density of cerebral tumours following intravenous injection of contrast media was measured by computer tomography and was evaluated quantitatively. The density increase of 158 tumours five minute after injection was between 0 and 29 CT units. There are considerable variations in density increase of various types of tumour, but the scatter is so wide as to preclude a diagnosis of tumour type. In 75 tumours repeated measurement of contrast changes were carried out for two hours following the injection. Again the variation differs with different types of tumour, but is not characteristic enough for exact clinical diagnosis. In 26 patients contrast concentrations were measured in the tumour and the blood and a pharmaco-kinetic compartmental analysis was carried out. In some tumours contrast changes can be explained by a single compartment model, whereas in others a two compartment model is necessary. Certain conclusions regarding the mechanism of contrast uptake can be reached.


[Image properties of computer tomography. III. Measurements on homogenous materials. Relationship of attenuation and scatter to various parameters (author's transl)].

The present paper investigates the variations due to various parameters on the image of homogeneous materials as obtained with the Somatom CT scanner. Sugar solutions were used with concentrations equivalent to the absorption values of soft tissues. Because of quantum noise, attentuation at various points is not uniform, but is distributed in a Gaussian manner round a mean value. Using the Evaluskop it was possible to determine the degree of scatter. It was shown that, with increasing density of the material, the scatter increased and that this can be reduced by subjecting the tomogram to a smoothing process. It was further shown how the scatter depends on various parameters, such as thickness and dose. The amount of scatter in a tomogram is important in determining the density gradation which can be a achieved.


[A comparative diagnostic study of malignant lesions of the liver by infusion angiography and percutaneous transhepatic portography (author's transl)].

The diagnostic effectiveness of percutaneous transhepatic portography (PTP) was evaluated in 21 patients with primary and metastatic liver carcinoma, who also had infusion hepatic angiography. The findings at PTP were compared with unequivocal tumor changes demonstrated at infusion hepatic angiography in all cases. PTP revealed tumors in 14 of 21 cases. The location, size and number of the tumor(s) were decisive for their detectability at PTP. Solitary lesions smaller than 2 cm in the central parts of the liver escaped detection, whereas lesions larger than 7 cm in the left lobe and 6 cm in the right lobe were demonstrated in all cases. Multiple metastases of 1--2 cm were detected in most cases. Lesions smaller than 4 cm were better shown by the sinusoidal phase at PTP, where lesions larger than 5 cm were better delineated by the portal venous phase.


[Nonsurgical production of intrahepatic portosystemic venous shunts in portal hypertension with the double lumen balloon catheter (author's transl)].

A nonsurgical production of intrahepatic shungs between the left portal and left hepatic vein was evaluated in twelve dogs with acute portal hypertension. Dilatation of the intrahepatic tract was achieved by means of a double lumen balloon catheter introduced into the portal system with the transjugular approach. The shunts proved to be effective in immediate reduction of increased portal pressure and no significant complications were encountered.


[Evaluation of hepato-biliary functional scintigraphy with 99mTc diethyle-IDA. Findings in normal livers (author's transl)].

Hepato-biliary functional scintigraphy was performed on 51 patients with normal livers after in the injection of 99mTc diethyle-IDA. The results were analysed according the morphological criteria (demonstration of the bile duct, intra-hepatic ducts, gall bladder and renal tract) and functional criteria (T max, half-time biliary excretion values, development of activity in the bile duct, in the gall bladder and in the gut). Demonstration of the bile duct and gall bladder was successful in all cases if the examination was carried out after an appropriate interval following food. 84.3% of patients showed a gall bladder excretary pattern of the tracer and 15.7% a gall bladder storage pattern. Correspondingly, bile appeared in the duodenum at 16.5 +/- 6.5 minutes (excretion) or 79.3 +/- 49.5 minutes (storage). The left hepatic duct was shown in 58.8%, the right hepatic duct in only 58.8%. Sixty minutes after the injection no activity could be determined in the bile ducts beyond the liver parenchyma. The gall bladder could be identified after 26.6 +/- 24.4 minutes, occasionally it was much later, up to 110 minutes. The liver function curve showed a Tmax level of 6.8 +/- 2.7 minutes and half value time of 15.8 +/- 6.7 minutes. At 5 minutes after injection the renal pelvis could be identified in 19.6%, but in no case was this still present beyond 15 minutes. Duodeno-gastric reflux was not demonstrated.


[Clinical result of thyroid scintigraphy and iodine estimations using a fluorescent technique (author's transl)].

The new technique of quantitative fluorescent scintigraphy was used for determining the regional distribution and concentration of stable intrathyroid iodine (127 I) in 96 patients. Average iodine concentration in normal people (20 individuals) without thyroid enlargement living in the Bavarian iodine-deficiency area was 0.38 +/- 0.07 mg/g. In 32 patients with simple goitres it was significantly lower at 0.17 +/- 0.06 mg/g. With this technique it was possible to separate two types of hyperthyroidism amongst 21 patients: those with low iodine concentration in the thyroid (0.15 +/- 0.08 mg/g) and those with high iodine concentration (0.42 +/- 0.12 mg/g) after iodine administration. The iodine concentration in decompensated autonomous adenomas in twelve patients was usually low (0.12 +/- 0.12 mg/g). On the other hand iodine concentration was high in the paranodular tissues and could be demonstrated on the fluorescent scintigram. The quality of the scintigram using this technique for concentrations below 0.1 mg/g is inadequate. In this situation good imates can be obtained by radionucleid scintgrams. The situation is reversed by previous administration of iodine.


[The radiographic appearances of the post-thrombotic syndrome and phlebographic control of the effect of treatment (author's transl)].

The phlebographic appearances of the post-thrombotic syndrome can be divided into four stages which are of importance with regard to diagnosis, treatment and prognosis. This division depends on the severity of the damage to the deep venous system. In addition it is necessary to define the superficial collateral circulation and to determine whether this is sufficient or not. Both before and after surgical treatment of the deep and superficial veins, it is necessary to define the situation by phlebography. The importance of serial phlebographic examinations during treatment, particularly with anticoagulants, is demonstrated by a series of cases.


[The significance of mastalgia in breast diagnosis (a pilot study on 706 women) (author's transl)].

Of 700 women on whom mammograms were carried out for various indications, more than half complained of mastalgia. A quarter of the women had suffered frequently from diffuse breast pain, and one third complained of mastaglia. A quarter of the women had suffered frequently from diffuse breast pain, and one third had had pain for years. One third complained of local breast pain. Changes in the mammogram amongst women with diffuse breast pain were no more common than in women without symptoms. There was no correlation between the frequency of pain and the extent of a "mastopathy". There were no changes which could be related to the pain. Similarly there was no difference in the frequency of biopsies or women kept under observation between those with breast pain and those without. This was also true for those with local breast pain, and also for those with clinically occult conditions. Breast size was of no significance for the occurrence of pain. Neither local nor diffuse breast pain is of any specific significance in breast diagnosis.


[New angiographic knowledge regarding the female breast (author's transl)].

In 67 patinets with abnormal mammograms, breast angiography was performed using a "lo-dose vaccum packed film screen system". The authors discuss the vascular finding within and outside the tumour.


[The accuracy of angiography in the evaluation of benign renal tumours (author's transl)].

The authors review the literature regarding the angiography of three benign renal tumours: adenoma, angiomyolipoma and angioma. Renal adenomas area rare. Oncocytomas can be classified with papillary adenomas; they are fairly characteristic and can be diagnosed pre-operatively. The tubular, and particularly alveolar form cannot be distinguished angiographically from a carcinoma. Angiomyolipomas (hamartomas) occur in tuberous sclerosis or may be found alone. Angiography can first of all be an aid to topographic classification. Its isolated occurrence may cause difficulties in differentiation from a carcinoma. Certain angiographic signs may enable pre-operative diagnosis: the demonstration of aneurysmal arterial changes, linear course of tumour veins and the frequency of a peri-renal haematoma. Angiolipoma is the renal tumour which is most frequently complicated by pre-renal bleeding. Capillary, plexiform or cavernous angiomas are rare. If the first two are large enough (2 cm), their homogenous hypervascularisation may permit preoperative diagnosis. The diagnosis of cavernous angiomas is more difficult.


Down's syndrome in Western Australia: cytogenetics and incidence.

235 cases of Down's syndrome were ascertained in a 10-year study of Down's syndrome in Western Australia. Although cytogenetic studies performed on 222 subjects confirmed that 95% of cases were trisomic due to nondisjunction, 4% were trisomic due to translocation, and 1% were mosaic, the ratio of inherited/sporadic translocations differed from that usually reported. Comparison of the results with those of an earlier Australian survey of Down's syndrome demonstrated a real fall in the incidence of Down's syndrome in Australia but no significant change in maternal age-specific incidences.


Phosphofructokinase (PFK) isozymes in man. I. Studies of adult human tissues.

Isozymic heterogeneity of human phosphofructokinase was investigated by means of ATP inhibition, immunoneutralization by antihuman muscle-type and antiliver-type phosphofructokinase antisera, solubility in (NH4)2SO4 solutions, and starch gel and polyacrylamide slab gel electrophoresis. The enzymes studied by these methods were purified from various normal and malignant human adult tissues by chromatography on blue Dextran Sepharose 4 B columns. From the results of these studied we suggest that three basic phosphofructokinase isozymes could exist: muscle-type, fibroblast-type, and liver-type isozymes. Muscle-type isozyme is the single form found in adult muscle, and is involved in the enzymes from heart, brain, red cell, and testis. Fibroblast-type isozyme is found mainly in the placenta, fibroblasts kidney, and some malignant tissues. Liver-type phosphofructokinase seems to be very definitely the predominant form in mature polymorphonuclear cells, platelets, and liver. Testis and red cell phosphofructokinase enzymes definitely include msucle-type aand liver-type subunits, associated in various hybrid forms.


Enterochelin (enterobactin): virulence factor for Salmonella typhimurium.

The ability of Salmonella typhimurium to synthesize enterochelin (enterobactin; ENT) affects its capacity to grow both in vivo and in vitro. An ENT mutant (96-1), blocked in the conversion of chorismate to 2,3-dihydroxybenzoate, was derived from SR-11, a strain of high mouse virulence. This mutant was unchanged in the other characteristics tested: colonial, biochemical, antigenic, and cellular. In contrast to SR-11, growth of this mutant in complement-inactivated human serum was strongly inhibited. However, addition of 5 muM ENT to the cultures relieved their inhibition. Viable counts of bacteria injected into the mouse peritoneal cavity showed that without ENT, growth of 96-1 was inhibited markedly; with ENT, the apparent growth rate of 96-1 exceeded that of SR-11. The 50% lethal dose (LD50) of 96-1 was 2 to 3 log units higher than that of SR-11. When ENT was injected, the ENT- mutant exhibited an ENT-dose-related decrease in its LD50. A single injection of 300 micrograms of ENT per mouse with the inoculum reduced the LD50 of 96-1 to that of the wild-type strain. These findings support the contention that ENT is a virulence factor for S. typhimurium.


Surface mucopolysaccharides of Treponema pallidum.

The viscous mucoid fluid that accumulates within syphilitic lesions may be due to breakdown of host tissue during infection, or may be synthesized by Treponema pallidum. Experiments were performed to investigate the acidic mucopolysaccharides that occur at the surface of T. pallidum (Nichols strain). These mucopolysaccharides were demonstrated by reaction with acidified bovine serum albumin and by agglutination with wheat germ agglutinin and soybean agglutinin. The polycations ruthenium red and toluidine blue influenced treponemal survival. Concentrations of both compounds at 200 mug/ml inhibited survival, whereas concentrations at 0.1mug/ml enhanced survival. The mucopolysaccharide concentration within the mucoid fluid that accumulates during intratesticular infection was determined by reaction with acidified bovine serum albumin; it ranged from 10,000 mug/ml to less than 8 mug/ml. The addition of this mucoid fluid to treponemal suspensions resulted in differing effects on T. pallidum survival. Some preparations were inhibitory, and others were stimulatory. Commercial preparations of hyaluronic acid and chondroitin sulfate at 400, 200, 100, and 50 mug/ml were detrimental to treponemal survival. The organisms exhibited pronounced clumping in the presence of the higher concentrations of hyaluronic acid. These clumps of treponemes were comprised of mucopolysaccharides as shown by acidified bovine serum albumin and toluidine blue reactions and by hyaluronidase degradation. Results are discussed in terms of the derivation and potential role of acidic mucopolysaccharides at the surface of T. pallidum.


Relationship of Treponema pallidum to acidic mucopolysaccharides.

Attempts were made to relate Treponema pallidum to the acidic mucopolysaccharides that occur in vivo within host ground substance and in vitro on the surface of cultured testicular cells. Infected testicular tissue was fixed and processed for transmission electron microscopy in the presence of ruthenium red. The use of this inorganic dye demonstrated the large quantity of mucopolysaccharide within testicular tissue and the intimate association of treponemes with this material. Wheat germ agglutinin and soybean agglutinin agglutinated freshly harvested trypsinized testicular cells and trypsinized cultured cells derived from normal rabbit testes (NRT). When stained with toluidine blue, both cell preparations were metachromatic. Prior treatment of cultured NRT cells with hyaluronidase slightly decreased their sensitivity to agglutination by wheat germ agglutinin and soybean agglutinin. Lectin agglutination, metachromasia, and hyaluronidase susceptibility indicated that freshly harvested testicular cells and NRT cells have surface-associated acidic mucopolysaccharides that are probably hyaluronic acid and chondroitin sulfate. A rabbit erythrocyte "sandwich" technique was devised to show that hyaluronidase removed wheat germ agglutinin receptors from the cultured NRT cells. Prior incubation of NRT cells with hyaluronidase, followed by the addition of T. pallidum, resulted in a reduction in numbers of treponemes attached to the NRT cells. The attachment of T. pallidum appears to be mediated through the acidic mucopolysaccharides on the surface of NRT cells. The findings are discussed in terms of the importance of host ground substance mucopolysaccharide to the syphilitic infective process.


Mucopolysaccharidase of Treponema pallidum.

Treponema pallidum (Nichols strain) exhibited mucopolysaccharidase activity. Acidic mucopolysaccharides were broken down more rapidly by viable treponemes than by heat-inactivated treponemes or membrane filtrates of treponemal suspensions. Ouchterlony immunodiffusion demonstrated the occurrence of antibodies to the hyaluronidase-like enzyme within syphilitic sera. After intratesticular inoculation of 2 x 10(7) to 6 x 10(7) treponemes, these anti-mucopolysaccharidase antibodies were detected between 9 and 35 days postinoculation. In addition, acidic mucopolysaccharides were present in the serum of infected animals 9 and 16 days postinoculation. Immune serum that contained antibodies to the mucopolysaccharidase restricted treponemal breakdown of acidic mucopolysaccharides. It has been previously demonstrated that immune rabbit serum contains a factor that blocks attachment of T. pallidum (Nichols strain) to cultured mammalian cells. This factor was effectively absorbed by prior incubation with bovine hyaluronidase. It is postulated that T. pallidum attaches to acidic mucopolysaccharides on the surface of cultured cells through the mucopolysaccharidase enzyme at the surface of the organisms. These findings are discussed in terms of the histopathogenesis of T. pallidum with applications to the healing immune response.


Effect of hydrocortisone, cyclophosphamide, azathioprine and methotrexate on cutaneous delayed and arthus hypersensitivity in the rat.

The effect of 4 immunosuppressive agents--hydrocortisone (HC), cyclophosphamide (CY), azathioprine (AZ) and methotrexate (MTX)--, on cutaneous delayed-type hypersensitivity (DTH) and Arthus reactions to the intradermal injection of ovalbumin (OA) in rats sensitized to OA in Freund's complete adjuvant (FCA) was studied. Multiple doses (daily for 4 days) were given either early, beginning on the day of sensitization, or late, beginning 9 days after sensitization. Single doses were given on the day of challenge with OA. All late multiple doses of drugs except HC depressed the DTH at 24 h in the following order of decreasing magnitude: MTX, CY, AZ. The DTH at 24 h was depressed by early multiple doses of MTX at all doses, by CY at all but the lowest dose, and by AZ at the intermediate dose; HC had no effect. When the drugs were given as single late doses, only CY at the lowest dose and MTX at the higher doses effectively depressed the DTH at 24 h. Increased Arthus reactions occurred after early and late multiple doses of HC and after a late single dose of CY at the highest dose. After late multiple doses the Arthus reaction was unaffected by either CY or MTX but was depressed by all doses of AZ. HC administered as 3 injections around the time of challenge markedly depressed the delayed and Arthus reactions. These results show that each of the 4 immunosuppressive drugs could depress DTH and Arthus reaction to OA, but the degree of depression varied with the time of drug administration relative to sensitization and challenge, and the dose of drug used. Histologic examination of skin test sites showed that an apparently negative reaction did not necessarily imply total absence of a cellular inflammatory response.


Experimental chronic serum sickness in rats. A model of immune complex glomerulonephritis and systemic immune complex deposition.

This article describes a method of immunization that produces chronic serum sickness in rats within a relatively short time. Fisher rats, which were immunized subcutaneously three times with bovine serum albumin (BSA) in adjuvant, responded with high titers of antibodies to BSA. 2 weeks after the third subcutaneous immunization, daily increasing amounts of BSA were injected either intraperitoneally or intravenously. When an intravenous dose of 2mg of BSA was reached, the rats were given daily intravenous injections of BSA for several weeks. This procedure, which avoided death from anaphylaxis, induced severe proliferative glomerulonephritis in all the rats and produced deposition of antigen-antibody complexes in many other organs besides the kidney. This highly reproducible model of experimental chronic serum sickness in inbred animals may have applications for the study of the mechanisms of immune complex disease.


[Development of acne following pregnancy (postgestational acne)].

A woman is reported, in whom acne appeared after pregnancy. There are similar conditions in postcontraceptive acne and in acne after pregnancy. For acne after pregnancy the term "postgestative acne" is proposed.


Integrating occupational health and safety into the health education classroom.

Given the startling number of job-related illnesses and injuries which occur every year, occupational health and safety, a hitherto neglected topic, deserves significant attention in the school health education curriculum. Youngsters need to be exposed to this field before they become indifferent or callous toward diseases and accidents in the workplace and while the opportunity still exists to weight health and safety considerations in selecting a career. In addition, when students take up regular employment, they cannot rely on industry, government, or organized labor to protect them fully from occupational illnesses and accidents; they must possess the skills and attitudes necessary to safeguard themselves. Occupational health and safety education in the schools can focus on general awareness, skill development, and job-specific information. The field can be easily and appropriately integrated with a number of current health education topics. Examples of integration are provided for eleven typical areas of a school health education curriculum.


Tyrosinemia without liver or renal damage with plantar and palmar keratosis and keratitis (hypertyrosinemia type II).

A boy of 3 2/12 years of age with Richner-Hanhart syndrome (plantar and palmar keratosis and chronic keratitis) was found to have hypertyrosinemia and to excrete the hydroxyacids derived from tyrosine. A diet poor in phenylalanine and tyrosine cured the skin and corneal lesions. Clinical and biochemical observations are reported.


Histochemical and ultrastructural characteristics of a new muscle fibre type in avian striated muscle.

The serratus metapatagialis (SMP) muscle of the pigeon has been studied histochemically and ultrastructurally. At the gross anatomical level the SMP is clearly divisible into a peripheral whitish band and a red portion comprised predominantly of 'pale' and 'red' fibres respectively. The pale fibres possess low succinate dehydrogenase, low mitochondrial content, absence of subsarcolemmal mitochondrial aggregates, low fat, moderate glycogen, high phosphorylase, low-to-moderate regular myofibrillar adenosine triphosphatase (M-ATPase), activation of M-ATPase following acid preincubation and jagged Z bands. On the basis of these characteristics, these physiologically slow muscle fibres have been termed 'Type I white or slow-twitch glycolytic'. The SMP red fibres, however, possess high aerobic as well as glycolytic capacity, high M-ATPase activity which is labile after acid preincubation and thick but straight Z bands; therefore, they are the 'Type II red or fast-twitch oxidative-glycolytic'.


Leg and splanchnic arteriovenous differences of plasma citrate in exercising man.

Arteriovenous concentration differences of plasma citrate, glucose, lactate, pyruvate, free fatty acids, acetoacetate, and 3-hydroxybutyrate were determined across the leg and the splanchnic vascular bed in six healthy subjects in postabsorptive state, during 30 min of exercise (60--70% work load) and 65 min of recovery. A release of citrate across the leg and an uptake across the splanchnic vascular bed were found. Citrate arterial-femoral venous difference at rest, -19 +/- 2 mumol/l was abolished after 5 min of exercise and rebuilt during continuous work to reach peak value, -30 +/- 3 mumol/l at 20 min recovery. During exercise increasing negative arterial-femoral venous citrate differences were inversely related to fractional glucose extraction across the leg. Arterial-hepatic venous citrate difference at rest, 10 +/- 2 mumol/l, increased twofold during recovery. The results agree with the concept that a citrate inhibition of phosphofructokinase may be of regulatory importance for muscular glycolysis and glucose uptake as well as for hepatic glycolysis and gluconeogenesis in man during exercise.


Contribution of rib cage and abdomen-diaphragm to tidal volume during CO2 rebreathing.

In man, there is wide interindividual range in the tidal volume response to CO2. To determine which (rib cage or abdomen-diaphragm) compartment had a greater influence on this range, ventilatory response to CO2 was measured, using Read's method, in eight men and two women seated in a constant-pressure body plethysmograph. Rib cage and abdominal tidal volume was simultaneously measured using magnetometers. Correcting for body size, the tidal volume response of the abdominal compartment was similar in all subjects, whereas that of the rib cage was larger in subjects with high tidal volume response to CO2; a significant correlation was found (P less than 0.01). Rib cage volume displacement lagged behind abdominal in all subjects; phase lag was greatest in the subject with the lowest ventilatory response to CO2. These results suggest that, at high levels of ventilation, a larger volume displacement of the rib cage may reflect a more effective coupling of the diaphragm pressure generator to it or alternatively a reduction in its impedance relative to the abdominal compartment.


Mobilization of sequestered metabolities into degradative reactions by nutritional stress in Neurospora.

The pools of arginine and ornithine rapidly disappear during nitrogen starvation of Neurospora crassa. Much of this disappearance can be accounted for by degradation catalyzed by preexisting catabolic enzymes. Purine degradation is also initiated by nitrogen metabolic stress. Mobilization of these compounds into degradative reactions does not appear to be a general response to nutritional stress since neither carbon starvation nor inhibition of protein synthesis elicits this response. It is suggested that nitrogen starvation may specifically alter the distribution of arginine and ornithine between vesicles and cytosol. This would be sufficient to initiate and maintain their degradation. These result suggest that compartmentation of amino acids provides a metabolic reserve to be utilized during periods of specific nutritional stress.


Levels of major proteins of Escherichia coli during growth at different temperatures.

The adaptation of Escherichia coli B/r to temperature was studied by measuring the levels of 133 proteins (comprising 70% of the cell's protein mass) during balanced growth in rich medium at seven temperatures from 13.5 to 46 degrees C. The growth rate of this strain in either rich or minimal medium varies as a simple function of temperature with an Arrhenius constant of approximately 13,500 cal (ca. 56,500 J) per mol from 23 to 37 degrees C, the so-called normal range; above and below this range the growth rate decreases sharply. Analysis of the detailed results indicates that (i) metabolic coordination within the normal (Arrhenius) range is largely achieved by modulation of enzyme activity rather than amount; (ii) the restricted growth that occurs outside this range is accompanied by marked changes in the levels of most of these proteins; (iii) a few proteins are thermometer-like in varying simply with temperature over the whole temperature range irrespective of the influence of temperature on cell growth; and (iv) the temperature response of half of the proteins can be predicted from current information on their metabolic role or from their variation in level in different media at 37 degrees C.


Mechanisms controlling the two phosphate uptake systems in Neurospora crassa.

The development of the high-affinity and low-affinity phosphate uptake systems of Neurospora crassa has been followed during germination and early growth. The ratio between the activities of the two systems became constant by the time exponential growth began, although the value of this ratio depended on the external phosphate concentration. The regulatory mechanisms controlling the systems were investigated by following the changes that resulted when exponentially growing germlings adapted to one phosphate concentration were shifted to a different concentration. The high-affinity system was derepressed under conditions of phosphate starvation, and inhibited irreversibly by feedback inhibition under conditions of over-supply. The low-affinity system was also derepressed and subject to feedback inhibition under comparable conditions, but, in contrast, inhibition of this system was reversible. A detailed description is given of the interplay between the systems during adaptation to changes in phosphate supply. Changes that occurred in the internal phosphate pool support the hypothesis that this metabolite is responsible for controlling the activities of the systems, either by triggering derepression of new uptake system synthesis or by inhibiting the existing system by feedback.


Specificity of uracil uptake in Neurospora crassa.

The specificity of uracil uptake was investigated in germinating wild-type conidia of Neurospora crassa. From comparative inhibition studies, several generalizations concerning the specificity of uracil uptake can be made. (i) The tautomeric forms of uracil analogs is an important determinant of recognition by the uptake system. (ii) Substituents at the 5 position of the pyrimidine ring may impose steric constraints on binding. (iii) The presence of a negative charge results in the loss of recognition. (iv) The double bond between the 5 and 6 carbons appears to be important for recognition. (v) Purine bases do not inhibit uracil uptake. Crude extracts of the transport-deficient mutant strain uc-5 pyr-1 were shown to have uridine 5'-monophosphate pyrophosphorylase activity comparable to that of the wild-type strain, suggesting that uracil uptake in Neurospora does not occur by a group translocation mechanism involving phosphoribosylation. Specificity studies of uridine 5'-monophosphate pyrophosphorylase indicated that phosphoribosylation was not an important determinant of the specificity of uracil uptake.


Glycogen phosphorylase from Neurospora crassa: purification of a high-specific-activity, non-phosphorylated form.

A highly active glycogen phosphorylase was purified from Neurospora crassa by polyethylene glycol fractionation at pH 6.16 combined with standard techniques (chromatography and salt fractionation). The final preparation  had a specific activity of 65 +/- 5 U/mg of protein (synthetic direction, pH 6.1, 30 degrees C) and was homogeneous by the criteria of gel electrophoresis, amino-terminal analysis, gel filtration, and double immunodiffusion in two dimensions. The enzyme had a native molecular weight of 180,000 +/- 10,000 (by calibrated gel filtration and gel electrophoresis) and a subunit molecular weight of 90,000 +/- 5,000 (by sodium dodecyl sulfate-polyacrylamide gel electrophoresis). Each subunit contained one molecule of pyridoxal phosphate. No phosphoserine or phosphothreonine was detected by amino acid analysis optimized for phosphoamino acid detection. The enzyme isolated from cells grown on high-specific-activity 32Pi (as sole source of phosphorus) contained one atom of 32P per subunit. All the radioactivity was removed by procedures that removed pyridoxal phosphate. Thus, the enzyme could not be classified as an a type (phosphorylated, active in the absence of a cofactor) or as a b type (non-phosphorylated, inactive in the absence of a cofactor). The level of phosphorylase was markedly increased in mycelium taken from older cultures in which the carbon source (glucose or sucrose) had been depleted. The polyethylene glycol fractionation scheme applied at pH 7.5 to mycelial extracts of younger cultures (taken before depletion of the sugar) resulted in co-purification of glycogen phosphorylase and glycogen synthetase.


Pleiotropic effects of ribosomal mutations for cycloheximide resistance in a double-resistant homocaryon of Neurospora crassa.

Pleiotropic effects of two ribosomal mutations for cycloheximide resistance were studied in a double-resistant homocaryon. The results obtained indicated that the combination of the two ribosomal mutations results in: (i) morphological abnormalities which suggest a severe distortion in the extension of cell walls and membranes; (ii) disturbance in the normal 60S-40S subunit ratio; (iii) decreased rate of cell mass production not necessarily associated with inbalance in the 60S-40S ratio; and (iv) cold sensitivity which does not interfere with mycelial mass production.


Troponin C-like protein in chicken gizzard muscle.

1. A troponin C-like protein was prepared from frozen chicken gizzard by preparative polyacrylamide gel electrophoresis and its apparent molecular weight was estimated to be about 15,500 daltons. 2. In urea gel electrophoresis, the mobility of the troponin C-like protein increased slightly in the presence of Ca2+, like that of skeletal muscle troponin C. On the other hand, the mobility of the the troponin C-like protein in glycerol gel electrophoresis, unlike that of skeletal muscle troponin C, was significantly decreased by Ca2+. 3. In alkaline gel electrophoresis, the troponin C-like protein formed a Ca2+-dependent complex with troponin I or troponin T from skeletal muscle. 4. The troponin C-like protein could neutralize the inhibitory effect of skeletal muscle troponin I on the Mg2+-activated ATPase of actomyosin from rabbit skeletal muscle, but could not confer Ca2+-sensitivity on the actomyosin in the presence of troponin I and troponin T from skeletal muscle.


Phosphorylation of uterine smooth muscle myosin permits actin-activation.

Myosin was purified from ovine uterine smooth muscle. The 20,000 dalton myosin light chain was phosphorylated to varying degrees by an endogenous Ca2+ dependent kinase. The kinase and endogenous phosphatases were then removed via column chromatography. In the absence of actin neither the size of the initial phosphate burst nor the steady state Mg2+-dependent ATPase activity were affected by phosphorylation. However, phosphorylation was required for actin to increase the Mg2+-dependent ATPase activity and for the myosin to superprecipitate with actin. Ca2+ did not affect the Mg2+-dependent ATPase activity in the presence or absence of action or the rate or extent of superprecipitation with actin once phosphorylation was obtained. These data indicate that: 1) phosphorylation of the 20,000 dalton myosin light chain controls the uterine smooth muscle actomyosin interaction, 2) in the absence of actin, phosphorylation does not affect either the ATPase of myosin or the size of the initial burst of phosphate and, 3) Ca2+ is important in controlling the light chain kinase but not the actomyosin interaction.


Intracellular protein degradation in Neurospora crassa.

In exponentially growing cultures of Neurospora crassa, the basal rate of protein degradation increases as the constant of the rate of growth decreases, so that in slow growing cells (mu = 0.13) the rate of protein degradation is about 25% of the rate of protein accumulation. During glucose starvation and shift-down transition of growth, the rate of protein degradation is greatly enhanced, and a moderate reduction (about 30%) of the ATP level is observed. Treatment of glucose-starved cells with 2-deoxyglucose reduces the ATP content by 70% and blocks protein degradation. The addition of cycloheximide, given at the onset of glucose starvation, prevents the enhancement of protein degradation; instead cycloheximide is without effect if added when proteolysis has already started. At a supraoptimal temperature (42 degrees C) the basal rate of protein degradation is not stimulated, contrary to the behavior observed in bacteria. Guanosine nucleotides, which appear to have a regulatory role for protein degradation in bacteria, are not found in N. crassa.


Cooperative binding of tropomyosin to muscle and Acanthamoeba actin.

Analyses of the binding of tropomyosin to muscle and Acanthamoeba actin by the use of Scatchard plots indicate that the binding exhibits strong positive cooperativity in the presence of Mg2+. The cooperative nature of the binding is not affected by the presence of 80 mm KCl, but appears to decrease somewhat in the presence of heavy meromyosin or subfragment-1. Heavy meromyosin, subfragment-1, and KCl each increase the binding affinity of actin for tropomyosin; depending on the experimental condition and the type of actin involved, the apparent binding constant, Kapp, is in the range of 1 to 4 x 10(6) M-1. Muscle actin cross-linked with glutaraldehyde failed to bind tropomyosin even when heavy meromyosin, subfragment-1, or KCl were added as inducers, although the cross-linked actin still markedly activated the heavy meromyosin ATPase.


Megacystis (prune-belly syndrome): sonographic demonstration in utero.

Oligohydramnios and megacystis were demonstrated sonographically at a gestational age of 18 weeks. This was confirmed radiographically by direct intrauterine injection of contrast medium into the enlarged fetal bladder. The fetus was aborted. Autopsy confirmed prune-belly syndrome with megacystis secondary to urethral obstruction. This case demonstrates the ability of ultrasound to diagnose a significant structural fetal abnormality early enough to allow termination of the pregnancy.


The dynein electrophoretic bands in axonemes naturally lacking the inner or the outer arm.

Two unconventional sperm models (all motile) have been studied. The first one has only the outer arm on the doublets (the gall midge, Diplolaboncus); the second one, has only a well-developed inner arm (the eel, Anguilla). Both are devoid of central tubules and radial spokes. The gall midge sperm yields a single electrophoretic band migrating similarly to the sea urchin dynein band A; a major high-molecular-weight band is obtained from eel sperm which co-migrates with the sea urchin dynein band B. The present picture is consistent with the localization of dynein in the axoneme--namely, of an A-like band in the outer arm, and of the B band in the inner arm. Moreover, the D band is present only in the eel, where gamma-links are present. ATPase activity was localized histochemically and found to be associated with both inner and outer arms, as well as with the gamma-links.


Chick brain actin and myosin. Isolation and characterization.

Brain actin extracted from an acetone powder of chick brains was purified by a cycle of polymerization-depolymerization followed by molecular sieve chromatography. The brain actin had a subunit molecular weight of 42,000 daltons as determined by co-electrophoresis with muscle actin. It underwent salt-dependent g to f transformation to form double helical actin filaments which could be "decorated" by muscle myosin subfragment 1. A critical concentration for polymerization of 1.3 microM was determined by measuring either the change in viscosity or absorbance at 232 nm. Brain actin was also capable of stimulating the ATPase activity of muscle myosin. Brain myosin was isolated from whole chick brain by a procedure involving high salt extraction, ammonium sulfate fractionation and molecular sieve chromatography. The purified myosin was composed of a 200,000-dalton heavy chain and three lower molecular weight light chains. In 0.6 M KCl the brain myosin had ATPase activity which was inhibited by Mg++, stimulated by Ca++, and maximally activated by EDTA. When dialyzed against 0.1 M KCl, the brain myosin self-assembled into short bipolar filaments. The bipolar filaments associated with each other to form long concatamers, and this association was enhanced by high concentrations of Mg++ ion. The brain myosin did not interact with chicken skeletal muscle myosin to form hybrid filaments. Furthermore, antibody recognition studies demonstrated that myosins from chicken brain, skeletal muscle, and smooth muscle were unique.


Localization of sarcoplasmic reticulum proteins in rat skeletal muscle by immunofluorescence.

Ca++-Mg++-dependent ATPase and calsequestrin, the major intrinsic and extrinsic proteins, respectively, of the sarcoplasmic reticulum, were localized in cryostat sections of adult rat skeletal muscle by immunofluorescent staining and phase-contrast microscopy. Relatively high concentrations of both the ATPase and calsequestrin were found in fast-twitch myofibers while a very low concentration of the ATPase and a moderate concentration of calsequestrin were found in slow-twitch myofibers. These findings are consistent with previous biochemical studies of the isolated sarcoplasmic reticulum of slow-twitch and fast-twitch mammalian muscles. The distribution of the ATPase in muscle fibers is distinctly different from that of calsequestrin. While calsequestrin is present only near the interface between the I- and A-band regions of the sarcomere, the ATPase is found throughout the I-band region as well as in the center of the A-band region. In comparing these results with in situ ultrastructural studies of the distribution of sarcoplasmic reticulum in fast-twitch muscle, it appears that the ATPase is rather uniformly distributed throughout the sarcoplasmic reticulum while calsequestrin is almost exclusively confined to those regions of the membrane system which correspond to terminal cisternae. Fluorescent staining with these antisera was not observed in vascular smooth muscle cells present in the cryostat sections of the mammalian skeletal muscle used in this study.


Effects of divalent cations on dynein cross bridging and ciliary microtubule sliding.

We recently demonstrated that addition of the divalent cation Mg++ to demembranated cilia causes the dynein arms to attach uniformly to the B subfibers. We have now studied the dose-dependent relationship between Mg++ or Ca++ and dynein bridging frequencies and microtubule sliding in cilia isolated from Tetrahymena. Both cations promote efficient dynein bridging. Mg++-induced bridges become saturated at 3 mM while Ca++-induced bridges become saturated at 2 mM. Double reciprocal plots of percent bridging vs. the cation concentration (0.05-10 mM) suggest that bridging occurs in simple equilibrium with the cation concentration. When microtubule sliding (spontaneous disintegration in 40 mM N-2-hydroxyethylpiperazine-N'-2-ethane sulfonic acid (HEPES), 0.1 mM ATP at pH 7.4) is assayed (A350 nm) relative to the Mg++ or Ca++ concentration, important differential effects are observed. 100% Disintegration occurs in 0.5-2 mM Mg++ and the addition of 10 mM Mg++ does not inhibit the response. The addition of 0.05-10 mM Ca++ to cilia reactivated with 0.1 mM ATP causes a substantial reduction in disintegration at low Ca++ concentrations and complete inhibition at concentrations greater than 3 mM. When Ca++ is added to cilia reactivated with 2 mM Mg++ and 0.1 mM ATP, the percent disintegration decreases progressively with the increasing Ca++ concentration. The addition of variable concentrations of Co++ to Mg++-activated cilia causes a similar but more effective inhibition of the disintegration response. These observations, when coupled with the relatively high concentrations of Ca++ or Co++ needed to inhibit disintegration, suggest that inhibition results from simple competition for the relevant cation-binding sites and thus may not be physiologically significant. The data do not yet reveal an interpretable relationship between percent disintegration, percent dynein bridging, and percent ATPase activity of both isolated dynein and whole cilia. However, they do illustrate that considerable (sliding) disintegration (60%) can occur under conditions that reveal only 10-15% attached dynein cross bridges.


Deficient 3 beta-hydroxy-5-ene steroid secretion by newborn infants.

Congenital adrenal hypoplasia is reported in two siblings. The first died at 16 months of purulent bronchopneumonia after a history of adrenal insufficiency. No gross adrenal tissue was found at autopsy and urinary steroids were not excreted in detectable amounts before death. In a subsequent uncomplicated pregnancy, extremely low estrogens were recorded in the last trimester. Analysis of steroids in the urine of the neontate by gas chromatography revealed virtual absence of 3 beta-hydroxy-5-ene steroids. These suggest hypoplasia of the fetal adrenal cortex. Metabolites of cortisol were excreted in normal amounts and responded adequately to ACTH stimulation. Neonatal hyponatremia was associated with subnormal excretion of corticosterone and aldosterone metabolites. It is proposed that in the perinatal period, the fetal zone is required for mineralocorticoid synthesis, possibly by providing essential precursor steroids, e.g. 21-hydroxypregnenolone.


Chick embryo pancreatic transplants reverse experimental diabetes of rats.

The effectiveness of xenogeneic embryonic tissue in the treatment of experimental diabetes has been investigated in rats. The splenic lobes (80) of 15- to 18-d-old chick embryos, composed almost exclusively of endocrine tissue, were implanted directly into the hepatic parenchyma of the rat recipient. The biochemical and metabolic changes in the recipients suggest that embryonic transplants of 15-d-old chick pancreases were able to significantly improve, for a prolonged period of time (18 mo), the diabetic state of nonimmunosuppressed rats. None of the recipients of 18-d-old embryos splenic lobes exhibited a long-term improvement of the diabetic state after transplantation. The complete destruction of the pancreatic B cells of the recipients was assessed by: (a) immunocytochemical investigations of the recipient's pancreas, (b) measurement of insulin in the liver and pancreas of the recipients and (c) in situ vascular perfusion of their pancreas submitted to high glucose challenge. The results suggest that pancreatic tissue of the 15-d-old embryos is immunologically immature lacking one or several lymphocyte subsets implicated in the afferent lood of "non-self" recognition.


Effects of exerimental right ventricular hypertrophy on myocardial blood flow in conscious dogs.

The effects of right ventricular hypertrophy on the overall and regional distribution of myocardial blood flow in the absence of an elevated coronary arterial driving pressure were evaluated in 18 concscious dogs subjected to a chronic pressure overload of the right ventricle induced by pulmonary artery constriction. The sustained pressure overload for duration of 4--6 wk or 4--5 mo resulted in significant increases in right ventricular mass (45 and 110%, respectively) and right ventricular fiber diameter (22 and 60%, respectively). Moreover, the presence of moderate and severe hypertrophy was associated with marked increases in transmural blood flow per gram to the right ventricle proportional to the observed increases in mass, i.e., of 36 and 109%, respectively, from a normal value of 0.67 +/- 0.04 ml/min per g, whereas left ventricular blood flow remained unaltered from a normal value of 1.00 +/- 0.06 ml/min per g. Despite the large increase in blood flow per gram to moderately and severely hypertrophied right ventricle, no significant changes in the ratio of capillary:muscle fiber number were observe. These data suggest that the development of right ventricular hypertroph is characterized by a sustained compensatory response of the coronary circulation to the augmented work load and mass, and that is not associated with a proliferative response of the vasculature supplying the enlarged ventricle.


An acid transporting enzyme in human gastric mucosa.

Isolation of a microsomal fraction from human gastric mucosa followed by density gradient centrifugation yielded a vesicular membrane preparation free of mitochondrial markers, containing a K+-activated, ouabain-insensitive ATPase with an activity of 20.7 mumol P1 released/mg protein per h. Sodium dodecyl sulfate gel electrophoresis showed that the human gastric membrane vesicles contained a major polypeptide of 110,000 daltons, which accounted for approximately or equal to 30% of the total protein stained and was phosphorylated by [gamma-32P]ATP and dephosphorylated in the presence of K+. Electron microscopy revealed the presence of vesicles with an average size of 0.13 micrometer in diameter. Addition of 0.65 microM ATP to this vesicular preparation resulted in the uptake of 17 nmol H+/mg protein which was dependent on the presence of K+. The gradient was dissipated by a combination of valinomycin and protonophore after consumption of the ATP. Incubation of fixed human fundic sections or human gastric biopsy with monospecific hog gastric membrane antibody followed by fluorescein-conjugated goat anti-rabbit gamma-globulin, showed fluorescent staining in the middle portion of the gastric glands. These data indicate that human stomach contains a H+ transport ATPase with characteristics similar to those established for lower species.


Concentrations of insulin and insulin receptors in the brain are independent of peripheral insulin levels. Studies of obese and streptozotocin-treated rodents.

In view of the potent influences of the central nervous system on glucose metabolism and on its hormonal regulators, and our recent finding of insulin and insulin receptors throughout the central nervous systsem, we have examined extreme conditions of hyperinsulinemia (obese mice) and hypoinsulinemia (streptozotocin-treated rats) with respect to changes in brain insulin and receptor content. Sprague-Dawley rats given streptozotocin (100 mg/kg body wt) developed severe diabetes and by 48 h showed no change in brain insulin. Rats given 65 mg/kg streptozotocin also had severe diabetes, but survived longer. Both at 7 d and at 30 d after streptozotocin treatment there was no significant change in brain insulin or in brain content of insulin receptors, despite the fact that peripheral hepatic receptors were elevated and pancreatic insulin was markedly depleted. The obese mice were studied at 8-10 wk when peripheral plasma insulin concentrations were 50-fold elevated and receptors on peripheral target cells were reduced to congruent with40-50% of normal; brain insulin concentrations and receptor content were indistinguishable from those of thin littermates. Thus, brain insulin, which is typically 10 times higher than plasma insulin concentrations, and brain receptor content, which is equivalent to receptor content on peripheral tissues, appears to be regulated entirely independently of hormone and receptor in the periphery. These findings are consistent with the hypothesis that insulin in the central nervous system is synthesized by the neural elements, and plays a role in the central nervous system which is unrelated to peripheral glucose metabolism.


Serotonin and the control of ventilation in awake rats.

In awake, unrestrained, intact rats, reserpine, para-chlorophenylalanine, 6-fluorotryptophan, and para-chloroamphetamine depleted whole brain serotonin and produced a substantial and sustained hyperventilation as evidenced by a 5--9 torr drop in PaCO2. Administration of 5-hydroxytryptophan to rats treated with para-chlorophenylalanine partially alleviated the hyperventilation. No change in ventilation was observed after alpha-methyltyrosine. 5,7-Dihydroxytryptamine produced contradictory results. On the basis of these pharmacological studies, we propose that some serotonin-mediated nerve transmissions might function under physiological conditions to inhibit the central nervous system output which controls normal breathing.