Influence of insulin on estrogen-induced responses in the r3230ac mammary carcinoma.

The R3230AC mammary adenocarcinoma was not dependent on insulin; tumor growth was equal to or greater in diabetic rats than in intact animals. However, tumor growth was reduced when daily doses of insulin were administered. Treatment with estrogen inhibited growth of the R3230AC carcinoma, either in diabetic rats or in intact animals simultaneously treated with insulin. The effects of insulin plus estrogen treatment appeared to be additive in causing inhibition of tumor growth. Tumors from diabetic rats showed few metabolic alterations as reflected by little or no changes in the activities of selected glycolytic enzymes, pyruvate kinase, phosphofructokinase, and hexokinase, nor any striking changes in the activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase, representing the pentose phosphate pathway. A modest reduction in the ratio of utilization of (1-14C)glucose: (6-14C)glucose was seen in vitro by tumors from diabetic rats. It was concluded that insulin, along with estrogen and prolactin, should be considered as a hormonal factor that influences growth of this automonous, hormone-responsive adenocarcinoma.


Effect of water-soluble adjuvants on in vitro lymphocyte immunization.

Water-soluble adjuvants prepared from Mycobacteriim smegmatis and human mixed mycobacteria strains C, DT, and PN were found to increase lymphocyte response in one-way mixed-lymphocyte culture and in vitro immunization to cultured human tumor cells. Phytohemagglutinin-induced lymphocyte blastogenesis, however, was depressed by water-soluable adjuvants.


Chlorozotocin, 2-(3-(2-chloroethyl)-3-nitrosoureido)-D-glucopyranose, an antitumor agent with modified bone marrow toxicity.

Chlorozotocin, 2-(3-(2-chloroethyl)-3-nitrosoureido)-D-glucopyranose, is a newly synthesized, water-soluble nitrosourea antitumor agent that is active against L1210 leukemia in mice. A 701% and a 401% increase in life-span were attained with a dose that was lethal to 10% of the animals (15 to 20 mg/kg, i.p.) in mice treated on Day 2 or Day 6 of L1210 tumor growth, respectivley. Sixity % of Day 2-treated mice and 30% of Day 6-treated mice survived for 90 days. At the maximally effective dose against L1210, chlorozotocin produced no significant depression in normal bone marrow DNA synthesis nor in peripheral neutrophil count, in contrast to a sustained greater than 90% inhibition in L1210 ascites cell DNA synthesis. If the antitumor activity and reduced bone marrow toxicity of chlorozotocin are confirmed in man the use of this compound would facilitate treatment of patients with neoplastic disease who have preexisting abnormal bone marrow function or would allow for the more effective use of a nitrosourea agent in combination with anticancer agents possessing more potent myelosuppressive properties.


Effect of the thyroid state on the enzymatic characteristics of cardiac myosin. A difference in behavior of rat and rabbit cardiac myosin.

The effect of thyroid state on the activity of myosin adenosinetriphosphatase (ATPase) was examined in the rat and the rabbit. Cardiac myosin from thyroxine-treated rabbits showed enzymatic properties characterized by high Ca2plus-activated ATPase activity, low activation energy, lower rate of inactivation at alkaline pH, and no activation by N-ethylmaleimide compared with the same properties in the normal rabbit; thyroidectomy did not affect the enzymatic properties of rabbit cardiac myosin. These findings suggest a difference in the myosin molecule at or near the active site, involving some sulfhydryl groups, between hyperthyroid and euthyroid rabbits. However, rat cardiac myosin showed a pattern of activity in the euthyroid state similar to that of the hyperthyroid rabbit and changed to the euthyroid type after thyroidectomy. These changes were specific for cardiac myosin, since no change was observed in skeletal myosin. It is unlikely that there are major differences in the myosin molecule associated with the two types of activity, since similar proportion and amino acid composition of the subunits of cardiac myosin were observed in the different thyroid states. Thus, we concluded that the administration of thyroxine to the rabbit stimulates the synthesis of new cardiac myosin with altered enzymatic properties and that synthesis of this type of cardiac myosin is maintained by the normal level of thyroid hormone in the rat.


Control of cardiac sarcolemmal adenylate cyclase and sodium, potassium-activated adenosinetriphosphatase activities.

A plasma membrane preparation purified from guinea pig ventricles without the use of high concentrations of detergents or structure-disrupting salts was used to compare the mechanisms of controlling sodium, potassium-activated adenosinetriphosphatase (Na, K-ATPase) and adenylate cyclase activities. The basal ATPase activity of 4-6 mu moles P1/hour mg-1 protein, measured in 120 mM NaC1 or KC1, was approximately doubled in 100 mM NaC1 plus 20 mM KC1. This increment, the Na, K-ATPase, was abolished by 10-5M ouabain, the K1 for ouabain being approximately 3 X 10-7M. 1-Epinephrine had no effect on Na, K-ATPase, but NaF was inhibitory. Adenylate cyclase, which had a basal activity of approximately 50% by NaC1 or KC1 alone at concentrations up to 0.2M. There was no additional stimulation of adenylate cyclase activity when na+ K+ included together. Both 1-epinephrine and NaF cause significant stimulation of adenylate cyclase, but neither basal nor activated cyclic AMP PRODUCTION WAS INFLUENCED BY OUABAIN. Half-maximal stimulation was seen at approximately 5 X 10-6M 1-epinephrine. Both the catecholamine and NaF increased the V-max ofcardiac plasma membrane adenylate cyclase without significantly influencing Km. Increasing Ca2+ in the range between 10-7 and 10-3M inhibited basal, 1-epinephrine-stimulated, and NaF-stimulated activities. Basal rates of cyclic AMP production were more sensitive to Ca2+ than was 1-epinephrine stimulation was increased from approximately 60% in 0.5 mM EGTA to approximately 150% in 10-7M Ca2+ and 400% in 10-5M Ca2+. The inhibitory effect of Ca2+ on adenylate cyclase activity may represent a negative feed back mechanism by which elevation of intracellular Ca2+ concentration lowers cellular levels of cyclic AMP and thus reduces Ca2+ influx into the myocardium.


Echocardiographic recognition of the mitral valve-posterior aortic wall relationship.

Aortic-mitral valve discontinuity has previously been described in double outlet right ventricle, endocardial cushion defect, single ventricle, tetralogy of Fallot, and prolapse of the mitral valve.  We are reporting two additional examples of aortic-mitral valve discontinuity including 15 cases of gross left ventricular dilation and a case of acute pneumococcal bacterial endocarditis with a large subannular erosion.  While nonspecific, aortic-mitral valve discontinuity is a clinically important sign that should be sought with slow-M-mode scanning and strip chart recording.


Precursors of sudden coronary death.  Factors related to the incidence of sudden death.

Precursors of sudden death were sought in men--1838 civil servants in Albany, New York, and 2282 residents of Framingham, Massachusetts--under continuous surveillance for 16 years. In men 45-74 years old there were 234 deaths attributed to coronary heart disease (CHD) of which 109 occurred within one hour of onset of symptoms. More than half of all deaths due to CHD occurred outside the hospital and about 80 per cent of these were sudden. Most were unheralded by prior symptoms of CHD. Persons at high risk of death from CHD, including sudden death, can be identified long before the terminal unexpected catastrophe. The same precursive stigmata exist in persons subject ot coronary attacks whether or not immediately fatal. The risk of sudden death in these two populations was positively correlated with high blood pressure, the electrocardiographic pattern of left ventricular enlargement, obesity, and heavy cigarette usage. Sudden death is a common and possibly incidental expression of lethal coronary heart disease. The potential candidate for sudden death cannot be confidently distinguished from the individual who succumbs more slowly of myocardial infarction. The inescapable conclusion is that the prevention of sudden death requires the prevention of coronary attacks.


Echocardiographic determination of left ventricular stress-velocity relations.

The time course of left ventricular (LV) circumferential stress and fiber shortening velocity (Vcf) were determined at 20 msec intervals in 30 patients from simultaneous recordings of LV pressure (micromanometer) and LV dimensions (echography). In 12 patients with normal LV function, endocardial and midwall maximal (max) Vcf, Vcf at peak stress, and endocardial mean Vcf were significantly greater than in eight patients with myocardial disease. Peak stress was less in the normal subjects (mean equal 241 gl/cm2, range 180 to 310 g/cm2) than in those with myocardial diseases (mean equals 371 g/cm2, range 280 to 513 g/cm2). Vcf was reduced in five out of seven patients with chronic LV volume overload, while peak stress ranged from normal in three to increased in four. Max Vcf, mean Vcf, and peak stress were normal in three patients with chronic LV pressure overload; Vcf at peak stress was normal in two. Good correlation was observed between angiographic determinations of mean Vcf and endocardial max Vcf, Vcf at peak stress and mean Vcf. Induced changes in preload in five patients (dextran infusion at constant heart rate) produced a 12.2 per cent increase in peak stress (P small than 0.05), and insignificant changes in max Vcf (3.7 per cent increase, P = NS), in Vcf at peak stress (5 per cent decrease, P smaller than 0.05), in mean Vcf (0.7 per cent increase, P = NS). Increasing afterload with angiotensin in seven patients (peak stress increased by 45 per cent, P smaller than 0.01) reduced max Vcf, Vcf at peak stress and mean Vcf by 33 per cent, 39 per cent respectively. Lowering afterload in one patient (amyl nitrite) produced an increase in Vcf. Improvement in Vcf was observed in all instances during positive inotropic stimulation (isoproterenol in three normals, digoxin in four with myocardial disease). Thre response of endocardial and midwall Vcf to loading and contractility were similar. In man Vcf is an index of myocardial contractility which is affected minimally by changes in preload but responds inversely to changes in afterload. Its sensitivity to acute afterload changes may, at times, limit its clinical applicability.


Changes in erythrocyte membrane ouabain-sensitive adenosine triphosphatase after renal transplantation.

1. Intracellular electrolytes, and erythrocyte membrane adenosine triphosphatase (ATPase) activity, was studied in twenty patients after renal transplantation. 2. The mean ouabain-sensitive ATPase activity in the erythrocyte membranes of the transplant patients was 122 nmol of inorganic phosphorus (Pi) h-1 mg of tissue-1 (SEM 14), compared with 62 nmol of Pi h-1 mg of tissue-1 (SEM 8) in a group of paired, healthy controls. 3. The increase in ouabain-sensitive ATPase was most marked in the 4 months after transplantation. However, a significant increase in ouabain-sensitive ATPase persisted for more than 8 months after transplantation. 4. This increase in ouabain-sensitive ATPase was associated with a decrease in intracellular sodium in the erythrocytes of the transplant patients.


Ostium primum defect in the adult: postoperative follow-up studies.

Twelve adult patients with ostium primum atrial septal defects (incomplete endocardial cushion defect) who underwent surgical repair of their lesions were evaluated in the late postoperative period. All had closure of the low-lying atrial septal defect, with suturing of the mitral valve cleft in 11 patients. Although the patients benefited symptomatically from the surgery, all had residual cardiac murmurs. Postoperative cardiac catheterization and left ventriculography in eight revealed successful closure of the atrial septla defect, but three demonstrated residual mitral insufficiency. In spite of the successful surgical repair in these patients, bacterial indocarditis prophylaxis should be continued in view of the residual murmurs and valvular abnormalities.


Evidence of subclinical heart muscle dysfunction in acromegaly.

A group of ten acromegalic patients, who had no history of heart failure, was studied to determine whether subtle carciac impairment may also be common. None had clinical evidence of coronary artery disease or severe hypertension. Systolic time intervals were recorded in each patient and compared with normal values predicted for sex and heart rate by our own controls and published data. The results indicate that measurable abnormalities in left ventricular performance are common in this sampling. Known duration and activity of disease (growth hormone levels at time of study) did not correlate with the time intervals. The results are consistent with cardiomyopathic effect of excessive growth hormone.


Isolation and biological characterization of fragments of human growth hormone produced by digestion with plasmin.

The biologically active component of plasmin digested human growth hormone consisted of residues 1-134 attached to residues 141-191 by the disulfide bond between residues 53 and 165. This large fragment of the hormone retained the in vivo capacity to stimulate weight gain and cartilage metabolism in hypophysectomized rats and exhibited the diabetogenic property of the native hormone in partially pancreatectomized, dexamethasone-treated rats. This fragment also retained the in vitro ability to stimulate protein synthesis and amino acid and sugar transport into isolated diaphragm muscle of hypophysectomized rats, Furthermore, a smaller peptide (residues 1-134) derived from the large fragment by reduction and carbamidomethylation of the disulfide bond retained high activity in in vitro systems and the in vivo capacity to stimulate cartilage metabolism provided the peptide was injected intravenously. Thus the present studies demonstrate that many of the in vivo and in vitro metabolic effects of human growth hormone on tissues of hypophysectomized rats can be elicited with a peptide comprising the aminoterminal 134 amino acid residues of native human growth hormone.


Age-dependent changes in the sensitivity of the rat to a diabetogenic agent (streptozotocin).

Changes of plasma glucose levels have been investigated in rats of 50, 70, 90, 110 and 150 g BW after the intravenous injection of 0, 40, 60, 80 or 100 mg/kg BW of streptozotocin. The effect of streptozotocin was dependent on the dose used and on the size of the animals. With all animal sizes studied, a transient acute hyperglycemic response to streptozotocin was observed at doses lower than those required to produce persistent hyperglycemia. Smaller animals required higher doses of streptozotocin in order to produce changes comparable to those observed in larger animals.


Enzymatic oxidation and reduction of C19-delta5-3beta-hydroxysteroids by hepatic microsomes. IV. Induction of DHA hydroxylases and aminopyrine N-demethylase in immature male rats by androgens.

The capacities of various C19 steroids for prematurely inducing the normal metabolic patterns of rat liver in adulthood (70 days old) have been studied with hepatic microsomes of 42-day-old males castrated on day 24, 30, 32, or 34 of life. Dehydroepiandrosterone 16alpha-hydroxylase activity was significantly reduced (P less than 0.05) by castration during this 10-day interval but the 7alpha- and 7beta-hydroxylases, the N-demethylation of aminopyrine, and cytochrome P-450 concentration were unaffected. Daily administration of testosterone stimulated the DHA 16-alpha- and 17beta-hydroxylases, aminopyrine N-demethylation, and increased the P-450 content, but suppressed the 7alpha-hydroxylase. These effects only appeared with more than 1 week of the continuous treatment. Testosterone was the most active of the androgens studied; dihydrotestosterone (DHT) increased the DHA 16alpha-hydroxylase to a lesser extent, but this steroid and etiocholanolone stimulated DHA 7alpha-hydroxylation; androsterone was totally ineffective. These data suggest that testosterone rather than DHT from pubertal testes plays a significant role in control of hepatic oxidative enzyme activities during puberty.


Effect of trimethylcolchicinic acid on the synthesis and excretion of proteoglycans in tissue culture.

The action of trimethylcolchicinic acid on the synthesis and excretion of proteoglycans has been studied on the L cell strain. The incorporation of precursors has been measured, and proteoglycans produced in the culture medium have been extracted and their concentration determined. The mucopolysaccharide components have been studied by electrophoresis. Control cultures produce hyaluronic acid, dermatan sulfate and very low concentrations of chondroitin 4-sulphate or 6-sulphate. Cultures treated with trimethycolchicinic acid (4 mu g/ml) produce hyaluronic acid, very high concentrations of chondroitin 4-sulphate or 6-sulphate and only traces of dermatan sulphate. So, trimethylcolchicinic acid does not modify the synthesis of hyaluronic acid: it considerably increases the production of chondroitin 4-sulphate or 6-sulphate and inhibits the production of dermatan sulphate. Protein fraction of the proteoglycans is proportionally increased in treated cultures, but there is no marked difference between amino acid concentrations of proteoglycans extracted from control and treated cultures. A slight fall in the cystine concentrations was the only change in the amino acid content of proteoglycans extracted from treated cultures. A hypothesis to explain these results is discussed.


Age-related changes, including synergy and suppression, in the mixed lymphocyte reaction in long-lived mice.

The mixed lymphocyte culture reaction represents the in vitro counterpart of the recognition phase of the graft-versus-host reaction, and of allograft rejection. The mixed lymphocyte culture reactivities of lymph node and spleen cells from all strains show a striking decline with advanced age. Furthermore, studies of "synergy" between subpopulations of T cells in the mixed lymphocyte culture reaction suggest that the cells of the recirculating lymphoid pool (T2 cells) in particular display a functional decline. Finally, spleen cells from old mice of appropriate strains inhibit or suppress the mixed lymphocyte culture reactivity of lymph node or spleen cells from young mice.


Enzymatic studies on the skeletal myosin A and actomyosin of aging rats.

Myosin A and actomyosin were isolated from the skeletal muscle of old and young rats. The velocity of the Ca2+ activated myosin A ATPase was increased in the case of the older animals. On the other hand the velocity of the Mg-2plus activated actomyosin ATPase was decreased in the skeletal muscle of the aging rats. At 5 X 10-5M EGTA concentration the inhibition of the Mg-2plus activated myosin B ATPase of the 1-month-old rats was two- to threefold smaller than that of the older animals. It was shown that the myosin A component of the actomyosin was responsible for the decreased troponin inhibition in the case of the 1-month-old rats. Between the ages of 1 month and 29 months the number of free myosin A SH groups decreases by 50%. The lipid peroxidation in the muscle of the 1-month-old animals.


Studies of the rate of regression of the glomerular lesions in diabetic rats treated with pancreatic islet transplantation.

Diabetes was induced in Lewis rats with streptozotocin. Six to eight months later glomeruli showed mesangial thickening: IgG, IgM and C3 were seen in large quantities in the mesangium by immunofluorescent microscopy. Ten animals then had successful pancreatic transplantation resulting in normal glucose and insulin levels within one to three weeks. Biopsies obtained within the first two weeks following transplantation demonstrated a significant reduction in mesangial thickening and in mesangial staining for IgG, IgM and C3. Three to four weeks after transplantation C3 staining was no longer detected. A gradual reduction in mesangial IgG and IgM localization continued so that by nine weeks following islet transplantation only minimal staining for immunoglobulins was present. Although mesangial thickening was reduced, this abnormality could still be detected in most animals six to nine weeks after transplantation. Three rats showed improvement in glomerular morphology within two weeks despite persistent hyperglycemia. These rats had normal insulin levels at this time. Islet transplantation in inbred diabetic rats effectively returns glucose and insulin levels to normal and results in rapid regression of the light microscopic and immunopathologic glomerular lesions. These studies support the concept of reversible mesangial dysfunction in diabetic rats.


Experimental hyperosmolar diabetic syndrome. Ketogenic response to medium-chain triglycerides.

The clinical features of the experimental hyperosmolar diabetic (EHD) rat model resemble those seen in the human syndrome--extreme hyperglycemia without ketoacidosis is common to both. The absence of ketoacidosis in the syndrome has been ascribed to both substrate (free fatty acid) deficiency and to interference with hepatic ketone body synthesis. The potential for hepatic ketone body synthesis in the experimental model has been directly assessed by challenging the EHD animals with medium-chain triglycerides (MCT) administered intragastrically. This neutral lipid, largely consisting of C8 and C10 fatty acids, leads to a dose- and thime-related increase in the plasma concentration of acetoacetate and beta-hydroxybutyrate. The EHD rats respond to MCT with an increase in plasma ketone bodies that rises to levels that are twice as high as those observed in normal rats receiving MCT and are equivalent to the levels seen in untreated ketoacidotic animals. These data indicate that hepatic medium-chain fatty acid oxidation and ketogenesis are unimparied in the EHD animal. An analysis of the factors responsible for the greater ketogenic response in the EHD rat reveals that moderate diabetes and dehydration enhance MCT-induced ketone body accumulation, while cortisol is without effect. The plasma free fatty acid concentration in EHD animals does not differ from normal rats, but is significantly lower than that seen in diabetic ketoacidosis. These data support the concept that a principal reason for the absence of ketoacidosis in the EHD syndrome is the limitation in availiability of substrate, free fatty acids, for ketone body synthesis.


A potent antimitogenic factor from group A streptococci.

A cytoplasmic component from group A streptococci produced complete suppression of human lymphocyte transformation induced by phytohaemagglutinin or the mixed lymphocyte reaction in vitro. It also suppressed antibody-forming cells in mice against sheep erythrocytes. The active substance was eluted as second and third fractions form Sephadex G-200 chromatography of the 100,000 g supernatant of sonically ruptured group A streptococci. The antimitogenic activity was not susceptible to trypsin, pronase, RNase or DNase digestion, but the activity was completely lost when it was sequentially digested, first with RNase and DNase and then with pronase. The active substance was not antigenic nor heat-labile at 56 degrees. It may be a protein component of a nucleoprotein.


Increased adenosine triphosphatase activity in platelets of asthmatic children.

Adenosine triphosphatase (ATPase) activities were compared in platelets of asthmatic and nonasthmatic children. Significantly elevated Mg2+- and Ca2+-dependent ATPase activities were found in particulate and soluble fractions of platelets from nonsteroid-treated asthmatic children compared to steroid-treated asthmatic and nonasthmatic children. The most pronounced increase (greater than twofold) occurred in the Ca2+-ATPase of the soluble fraction which contains platelet contractile protein. Intact cell surface of ecto ATPase activity was not significantly increased in platelets of asthmatic children. The findings are consistent with adrenergic imbalance in asthma involving depressed adenylate cyclase activity (beta-adrenergic) and increased ATPase activity (alpha-adrenergic) and may relate to abnormal platelet aggregation patterns.


Effect of vibration on sulfomucopolysaccharide metabolism in the eye.

The metabolism of 35S sodium sulfate was studied in the eyes of guinea pigs and rabbits subjected to vibration. The investigations included determination of radioactivity of whole eyeballs of guinea pigs and in single eyeball tunics of rabbits, i.e., retina-choroid-sclera investigated jointly as a tissue complex, and cornea and lens studied separately, besides that, autoradiographic investigations were performed. The animals were subjected to a vertical, sinusoidal vibration of 42 Hz. frequency and 1 mm. amplitude. The duration of one exposure was three hours and they were repeated daily for three to six days. Incorporation of the isotope into the eyeballs of animals subjected to vibration was decreased and this decrease was related to the length of exposure suggesting that vibration changes the metabolism of sulfomucopolysaccharides in the eye.


Reduction products of spectinomycin.

The two epimers of dihydrospectinomycin have been separated and identified structurally. Four tetrahydrospectinomycins have also been prepared.


Changes in the glutathione thiol-disulfide status of Neurospora crassa conidia during germination and aging.

Improved methods were developed for the determination of reduced glutathione (GSH), glutathione disulfide (GSSG), and protein-glutathione disulfide (PSSG) and applied to determine the glutathione status at various stages of the asexual life cycle for the band strain of Neurospora crassa. The GSH-GSSG ratio in freshly harvested dry conidia was found to be about 150 but decreased to around 6 when dryconidia were aged (stored) for 10 days after harvest. When conidia were germinated, this ratio increased to about 300 during the first 10 min of the 6-h germination process. In mycelia, during log-phase growth, the ratio was about 10-3. Changes in the ratio occurred primarily through changes in the GSSG content, which ranges from about 0.023 (mycelia) to 2(10-day aged conidia) mumol per g (dry weight) of residue, whereas GSH levels varied by a factor of about two. The PSSG content varied from 0.02 (mycelia) to 0.6 (10-day aged conidia) mumol per g (dry weight) of residue and generally paralleled the GSSG content. The results demonstrate the potential importance of thiol-disulfide reactions as a mechanism for the control of physiological properties associated with dormancy, and the observed changes in GSSG level are found to be compatible with the view that GSSG plays a role in the regulation of protein synthesis through control of polysome formation.


Neurospora crassa temperature-sensitive mutant apparently defective in protein synthesis.

A temperature-sensitive mutant of Neurospora was isolated which appeared to be defective in the initiation of protein synthesis. The defect in mutant 34Cts was apparently due to a single gene mutation, and was recessive in heterokaryons. Conidial germination was normal and hyphal growth was nearly so in the mutant at 20 C, but both were greatly inhibited at 35 C. After 15 min at 35 C there was a reduced rate of protein synthesis, followed by decreases in ribonucleic acid and deoxyribonucleic acid synthesis. The percentage of ribosomes in polysomes declined at 35 C and the average size of polysomes decreased. Because the decrease in protein synthesis, it was believed that some part of the translational system may be affected by the mutation. Mutant 34Cts was given the designation psi-1.


Glucose transport-deficient mutant of Neurospora crassa with an unusual rhythmic growth pattern.

A new mutant of Neurospora crassa has been isolated from the patch strain. The phenotype of the new mutant includes the periodic production of sparse and dense aerial hyphae and the inability to utilize carbohydrates. The biochemical lesion was identified as a deficiency in the low-affinity glucose transport system. The high-affinity transport system appeared normal. External conditions such as medium composition, temperature change, and light-dark cycles affected the rhythm of hyphal production to a different extent in the mutant from that in the parental strain. The lesion in the mutant was mapped on the far left arm of linkage group IV.


The relationship between the bovine heart mitochondrial adenosine triphosphatase, lipophilic compounds, and oligomycin.

The lipid-free particulate preparations of the mitochondrial ATPase require phospholipid for activity and can be inhibited by oligomycin, as has been demonstrated previously. In this communication a steady state analysis of the activation of a particulate preparation of the ATPase by phospholipids and its subsequent inhibition by oligomycin has been carried out. The relative affinity of the ATPase for purified phospholipids has been determined by measuring the Km for activation (Ka) for several phospholipids. The Ka values varied from 30 to 100 mum. The Vmax in the presence of phosphatides varies from 0.29 to 1.11 mumol ATP hydrolyzed/min/mg of protein; no correlation is noted between the relative affinity of the enzyme for a phospholipid and the V max value. Higher V max values are noted with the more acidic phospholipids, however. Sodium dodecyl sulfate and monoolein also activate with Ka values of 25 and 800 mum, respectively. Diglycerides, however, do not activate. With all lipids the ATPase activity stimulated is oligomycin-sensitive. The Ki values for oligomycin range from 0.1 to 0.6 mum. Oligomycin is a competitive inhibitor with respect to all the phospholipids tested except phosphatidylethanolamine and phosphatidyglycerol. It is also competitive with respect to sodium dodecyl sulfate (k-i equals 0.94 mum). In reciprocal plots of activity versus ATP concentration, with and without oligomycin, an intercept consistent with either mixed or partial noncompetitive inhibition kinetics is noted. Comparable K-i values for oligomycin are obtained when calculated assuming either mixed or partial noncompetitive inhibition. The Km for ATP is the same in the unactivated and the lipid activated particulate ATPase; the value obtained is slightly lower than the Km for ATP in the solubilized, purified ATPase. Using a spectrophotometric assay the time required for activation with phospholipid and inhibition with oligomycin has also been determined. This investigation suggests the possibility that activation of the ATPase is due  a position to interact with the water-soluble substrate. Consistent with the above suggestion is the supposition that the lipids do not necessarily confer inhibitor sensitivity to the ATPase, but rather allow an oligomycin-sensitive activity to be expressed.


A solid-liquid biphasic model for characterization of properties of muscle and platelet contractile proteins.

Actomyosin, myosin, and actin from different sources are adsorbed, apparently as a monolayer, by polystyrene particles teins for 1 mg of Lytron were about 10-7 liters mol-1, while heterogeneity indices (alpha) varied from 0.70 to 1.0 presumably as a function of spontaneous aggregation in the liquid phase. Adsorption was irreversible. Orientation of absorbed molecules permitted association of bound muscle actin with platelet or muscle myosin. The association constant of the former reaction was 2.78 times 10-6 liters mol-1. Enzymatic properties of adsorbed actomyosin, Mg2+ATPase activity was abolished, but association of myosin with bound actin, or association of actin with bound myosin was accompanied by restoration of Mg2+ATPase activity. Every subunit of F-actin strands, unless F-actin had been fully depolymerized to G-actin, could bind myosin and activate Mg2+ATPase activity. Immunogenic characteristics of muscle myosin were enhanced by Lytron adsorption. Elicited antibodies showed selective specificity for an antigenic determinant located near or at the actin combining site of muscle myosin. Antibodies did not react with actomyosin. Antibodies prevented association of actin with muscle myosin because they inhibited both superprecipitation and development of Mg2+ATPase activity.


The transarticular graft for infantile pseudarthrosis of the tibia. A new technique.

Fourteen cases of pseudarthrosis of the tibia in childhood presented at a hospital in Burma over a period of eight years. The ages of the patients ranged from one month to seventeen years. Nine were treated by a pointed graft driven into the medullary cavity of the distal tibia, and usually across the ankle joint into the body of the talus, before fixation to the proximal tibia. In six of the nine union was secured, but one case required a second grafting. Transarticular segments of graft showed a marked tendency to undergo absorption. No significant deformity was observed to follow central penetration of the growth plate and epiphysis of the lower tibia.


Circulating concentrations of dehydroepiandrosterone and dehydroepiandrosterone sulfate during puberty.

In order to quantitate the chronological change in circulating dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DS) levels during the period of sexual maturation, serum DHEA and DS concentration (3-5 PM) in 76 boys and 65 girls (ages 8 to 15) as well as in adult male and female subjects were measured by a specific and sensitive radioimmunoassay technique. Our data show a progressive and parallel increase in serum DHEA and DS concentrations in boys, and adult male levels were reached earlier for DHEA (age 13) than for DS (age 14). From age 8 to adult male, there was a 2.6-fold increase in DHEA (1.52 plus or minus 0.16 ng/ml to 3.91 lus or minus 0.34 ng/ml) and a 7.7-fold increase in DS (0.40 plus or minus 0.08 mug/ml to 3.09 plus or minus 0.36 mug/ml). The rise of DHEA and DS was not in a parallel fashion in girls; while DS rose progressively, DHEA showed an abrupt increase between 11 and 12 yr of age. Adult female range was reached by age 12 for DHEA and by age 15 for DS. From age 8 to adultfemale there was a 2.3-fold increase in DHEA (1.93 plus or minus 0.19 ng/ml to 4.49 plus or minus 0.76 ng/ml) and a 7.5-fold increase in DS (0.29 PLUS OR MINUS 0.05 MUg/ml to 2.17 plus or minus 0.34 mug/ml). The role of increased adrenal androgens inthe sexual development during early stages of puberty is discussed.


Studies on human plasma C1 inactivator-enzyme interactions. I. Mechanisms of interaction with C1s, plasmin, and trypsin.

This study has explored the nature of the molecular events which occur when C1 inactivator, a human plasma inhibitor of the complement, kinin-forming, coagulation, and fibrinolytic enzyme systems, interacts with C1s, plasmin, and trypsin. Purified inhibitor preparations demonstrated two bands, when examined by acrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS). The molecular weights of the major and minor bands were 105,000 and 96,000 daltons, respectively. The minor component appeared to be immunologically and functionally identical to the main C1 inactivator component. Loss of C1s and plasmin functional activity was associated with the formation of a 1:1 molar complex between the inhibitor and each enzyme. These complexes were stable in the presence of SDS and urea. The light chain of both these enzymes provided the binding site for C1 inactivator. Complex formation and enzyme inhibition occurred only with native and not with an inhibitor preparation denatured by acid treatment, thereby demonstrating the importance of conformational factors in the enzyme-inhibitor reaction. Although peptide bond cleavage of the C1 inactivator molecule by C1s was not documented, plasmin was found to degrade the inhibitor with the production of several characteristic derivatives. At least one of these products retained the ability to complex with C1s and plasmin. Trypsin, which failed to form a complex with C1 inactivator, degraded the inhibitor in a limited and sequential manner with the production of nonfunctional derivatives one of which appeared structurally similar to a plasmin-induced product. These studies therefore, provide new information concerning the molecular interactions between C1 inactivator and several of the proteases which it inhibits.


Studies on human plasma C1 inactivator-enzyme interactions. II. Structural features of an abnormal C1 inactivator from a kindred with hereditary angioneurotic edema.

The function and several of the structural features of the C1 inactivator protein isolated from the plasma of a mother and daughter with the variant form of hereditary angioneurotic edema have been examined. These abnormal inhibitors shared immunologic identity with the normal C1 inactivator protein; however, they were inactive in inhibiting the functional activity of C1s. Analysis of the abnormal inhibitors by sodium dodecyl sulfate (SDS) acrylamide gel electrophoresis suggested that each consisted of a single polypeptide chain, the mobility of which was slower than that of the normal C1 inactivator. The apparent molecular weight of the patients' inhibitors was 109,000 daltons as contrasted to 105,000 daltons, that of the normal C1 inactivator. The abnormal inhibitors failed to form a complex with C1s or plasmin as analyzed by SDS-acrylamide gels. The large proteolytic derivatives resulting from the plasmin- and trypsin-induced degradation of the abnormal inhibitors were approximately 3,000 daltons heavier than the corresponding products derived from normal C1 inactivator. Thus, the structural abnormality identified appeared to be a property of the core molecule. Treatment of the inhibitors with neuraminidase failed to demonstrate a difference between the normal and patient-derived C1 inactivator molecule. Neither were major differences found between the amino acid composition of the defective and normal inhibitors; however, the acidic amino acids tended to be higher in the patients' inhibitors, and the phenylalanine content lower. Thus, these studies have identified both structural and functional abnormalities in the C1 inactivator protein isolated from two related patients with hereditary angioneurotic edema. Examination of the interaction between endopeptidases and the inhibitors has further delineated the abnormal structural features.


Sodium- and potassium-activated ATPase. A possible target of aldosterone.

Na-K-ATPase activity was measured with an ultramicromethod in single portions of the proximal and distal convolution and of the thick ascending limb of Henle from adrenalectomized rats and after treatment with 5 mug aldosterone per 100 g body wt. The activity in all tubular structures returned to normal within 1 h after injection. This rapid activation of Na-K-ATPase induced by hormone was completely prevented by actinomycin D and cycloheximide. It appears that this aldosterone effect on Na-K-ATPase requires an intact protein synthetic process.


Werner's syndrome: autopsy report of one case, with a review of pathologic findings reported in the literature.

The autopsy findings in a 29-year-old male with Werner's syndrome are presented, with a review of similar data on 17 autopsy cases reported in the literature. The pathologic findings in this new case were scleroderma-like skin atrophy, arteriosclerosis, and atrophy of the endocrine glands (including the genital organs). In the reported cases of Werner's syndrome, as in the present example, the authors were unable to identify any responsible organ or system. However, they suggest that connective tissue, widely distributed throughout the entire body, may play an important role. The possible abnormal metabolism of connective tissue in Werner's syndrome deserves further study.


Alloimmune cytotoxic T cells: Evidence that they recognize serologically defined antigens and bear clonally restricted receptors.

Murine  T cells immunized with allogeneic cells exert a cytotoxic effect on appropriate target cells, as measured by 51-Cr release. Lysis of the 51-Cr-labeled target can be inhibited by addition to the assay of unlabeled cells which bear target antigens. With variants of lymphoid tumors which express different amounts of serologically defined H-2 antigens as competitors in the assay, a positive correlation is shown to exist between the amount of serologically defined antigen and the degree of inhibition of T cell-mediated lysis. The immunized small lymphocytes are shown to be very poor inhibitors of 51-Cr release from target cells which are more susceptible to T cell-mediated lysis. This is interpreted as showing that small lymphocytes are bound very poorly by cytotoxic T cells. With H-2 cross-over strains which carry only the H-2K or H-2D antigens which a cytotoxic population is directed against, it is shown that, 1) approximately equal amounts of cytotoxicity are directed against the K and D antigens, and 2) separate cytotoxic T cells recognize the K and D antigens. Thus, by this criterion, cytotoxic T cells are monospecific and therefore do not acquire their antigen-specific receptors cytophilically.


Mixed leukocyte culture reactivity in operationally tolerant rats: Relationship of lymphocyte-mediated reactivity and serum-blocking activity.

Tolerance to Brown Norway (BN) allografts was induced in Wistar Furth rats by neonatal inoculation of BN bone marrow cells or mixtures of (W/Fu x BN)F-1 hybrid spleen and bone marrow cells. Lymphoid cells from rats in which operational tolerance had been induced (maintenance of BN skin graft for more than 100 days) were studied for mixed leukocyte culture (MLC) reactivity. Peripheral blood lymphocytes from 10 of 25 W/Fu rats operationally tolerant to BN skin grafts showed MLC reactivity when exposed to BN antigens in vitro, implying that some degree of MLC reactivity is compatible with prolonged skin graft survival. These same rats also showed cytotoxic activity to BN fibroblasts in vitro regardless of their MLC status. MLC is quantitatively decreased and possibly qualitatively altered as compared to that of control W/Fu lymphocytes. The decrease was specific for the tolerated antigens. Serum from the tolerant rats inhibited cytotoxic but not normal MLC reactivity of W/Fu cells against BN antigens.


Inhibition of mitogen stimulation of human peripheral blood leukocytes by Vibrio cholerae enterotoxin.

It has been found that the enterotoxin (choleragen) of Vibrio cholerae, strain 569B, can interfere with Phytohemagglutinin-P, pokeweed mitogen and concanavalin A stimulation of human peripheral blood leukocytes. The viability of cultured cells was not affected by the toxin. The toxin does not interfere with stimulation by direct competition for mitogen receptor sites. The ability of choleragen to inhibit stimulation by mitogens declines with time after initiation of stimulation. The biologically inactive, spontaneously formed, derivative of choleragen, choleragemoid, did not inhibit mitogen stimulation. However, choleragenoid did block the inhibition of stimulation caused by choleragen. Choleragenoid did not block inhibition of mitogen stimulation by a lymphocyte chalone preparation indicating that a different mechanism may be involved with the chalone. Since the diverse biological effects of choleragen are all believed to result from its interaction with cell membrane receptors followed by activation of adenyl cyclase, the results add to evidence which suggests that increases in the intracellular concentrations of 3',5'-adenosine cyclic monophosphate diminishes the mitotic activity of cells.


Suppression of maternal responsiveness to paternal antigen by maternal plasma.

The effect of plasma from multigravida women on the expression of cellular hypersensitivity to paternal antigens was investigated. It was found that autologous, but not homologous, maternal plasma specifically blocked MIF production by maternal lymphocytes using their husbands' cells as an antigenic stimulus. The blocking activity could be absorbed out by repeated incubation with paternal cells. Sephadex G-200 fractionation of maternal plasma showed the blocking activity to be in the IgG fraction. The presence of specific blocking factor(s) in maternal plasma which prevent reactivity to paternal antigens may explain in part the success of the fetus as an allograft.


The allogeneic effect: M-locus differences substitute for differences in the H-2 major histocompatibility complex.

The primary immune response against sheep red blood cells in T cell-deficient spleen cell cultures from nude mice was tested in the absence and presence of allogeneic spleen cells. The allogeneic spleen cells differed either in regard to the major histocompatibility complex (H-2) or only with respect to the M-locus. Surprisingly the M-locus different spleen cells were almost as efficient in enhancing the anti-sheep red blood cell response in nude cultures as were the cells differing on the complete H-2 complex. Evidence is presented that AKR anti-theta serum sensitive T cells are responsible for the M-locus-dependent effect edscribed. This effect is shown to be mediated by a factor released from actived T cells stimulated in M-locus different mixed lymphocyte cultures. Since almost identical parameters have been observed in both the M-locus-dependent situation as in the "classical" allogeneic situation we concluded that an allogeneic effect can be induced by T cells responding to a complete set of the major histocompatibility complex (H-2) as well as to lymphocyte-activating determinants (M-locus) alone.


Functional heterogeneity among the T-derived lymphocytes of the mouse. IV. Nature of spontaneously induced suppressor cells.

When spleen cells are cultured for 4 days in the presence of fetal bovine serum, T-cells are generated which nonspecifically suppress the humoral responses of non-precultured cells to a variety of antigens. These T cells can be generated from both short-lived, sessile T1 cells and long-lived, recirculating T2 cells, and thus appear similar to suppressor T cells activated by concanavalin A.


Changes in the immunochemical properties of highly purified properdin in human serum.

The fate of highly purified properdin (P) upon introduction into normal human serum or properdin-depleted serum (RP) was investigated. It was observed that, concomitant with the activation of the alternate pathway components, properdin underwent immunochemical alterations characterized by a shift in mobility from gamma2 to beta2 position and by an increase in the sedimentation rate from 5.1S to between 6.8 and 9.3S. The immunoelectrophoretic behavior of C3 was also altered with the appearance of a beta2 arc in addition to the beta1C arc. The immunochemical properties of altered P resemble those of "native" properdin in fresh serum. The principle in serum (designated factor F) mediating these changes is a euglobulin with an approximate sedimentation rate and molecular weight of 9.0S and 250,000 daltons, respectively. The alteration in the immunochemical properties of P may be due to aggregation of P molecules or a complex formation between P and a serum euglobulin (probably C3) mediated by factor F and it is associated with loss of ability of P in initiate the alternate pathway of complement activation upon interaction with serum.


Percutaneous absorption on the relevance of in vitro data.

The use of in vitro preparations of human skin to study percutaneous absorption is widespread.  Yet, up to the present time, little has been done to systematically validate this model and demonstrate the extent to which it mimicks in vivo absorption.  In this study, the permeability of 12 organic compounds has been evaluated in excised skin and the results compared to those obtained previously by others in living man.  With special emphasis being given here to duplicating in vivo conditions, it was possible to demonstrate an excellent qualitative agreement between the two methods.  In all cases, the absorption pattern determined in vitro rather precisely paralleled the pattern which was obtained in vivo.  Quantitative agreement between the two sets of data was less than perfect, although the in vitro method adequately distinguished compounds of low permeability from those of high permeability and ranked then in approximately the same order found in vivo.  This systematic comparison of in vitro with in vivo data was clearly shown how accurately in vitro absorption studies can reflect the living state.


Distribution of serotypes of hepatitis B surface antigen in an institution for the mentally retarded.

The serotypes of hepatitis B surface antigen present in patients at the Lynchburg Training School and Hospital were determined by counterelectrophoresis. Hepatitis B surface antigen was detected by counterelectrophoresis in 72 of 82 samples that were positive by complement fixation or passive hemagglutination techniques. Of the isolates that were serotyped, 51 (71 percent) were ad, and 21 (29 percent) were ay; thus the ad:ay ratio was about 2.4:1. The incidence of the ay serotype was significantly higher in females and in patients with Down's syndrome. The ay serotype was not randomly distributed in the institution but was clustered in two of seven female wards and four of 11 male wards, all of which contained younger patients who had been institutionalized at an early age.


Hormone and hormonal agents in the treatment of aggression.

Evidence for the role of androgens in the male aggressive and sexual behavior is reviewed. Medroxyprogesterone acetate (MPA; Provera, Upjohn) has a marked antiandrogen property; it is effective in lowering the testosterone level and controlling certain otherwise intractable sex deviations. The finding in 6 patients treated for sex deviation are summarized. The effects of MPA in the treatment of 11 temporal lobe epileptics and 5 other patients with severe angry-aggressive behavior disorder are reported. Most temporal lobe epileptics responded well to MPA. Weight gain and earlier sleep were consistent side effects. The values of plasma testosterone, serum luteinizing hormone, and urinary 17-ketosteroids were decreased by the treatment. Four patients were XYY individuals with lack of control over their sexual-aggressive or angry-aggressive impulses.


Peripheral nerve regeneration in experimental diabetes.

Observations have been made on the regeneration of myelinated fibres in the sural nerve of streptozotocin-induced diabetic rats and age-matched non-diabetic control animals at 3, 6 and 18 weeks after a localized crush lesion. Morphometric studies on the regenerated fibres revealed no differences in the total fibre count, size-frequency distribution or average diameter at 18 weeks after injury. The degree of myelination was assessed by relating the number of myelin lamellae to axon circumference. The relationship was found to be approximately linear. There was a possible slight lag in myelination at 3 weeks after injury in the diabetic animal, but no difference was detectable at 6 and 18 weeks after injury.


Silastic abdominal patch for temporary hepatomegaly in Stage IV-S neuroblastoma.

Of our 174 neuroblastoma patients, 11 were classified as Stage IV-S. The primary tumor is usually small and there is widespread disease in the liver, skin, bone marrow, or any combination of these. The prognosis is favorable and radiation and chemotherapy should be avoided if possible. In some of these children the rapidly enlarging liver may cause respiratory distress and vena caval compression. The creation of a ventral hernia by means of a Silastic patch is a useful, temporary procedure during the life-threatening period of rapid growth and increased intra-abdominal pressure. Closure is simple once the liver has returned to normal.


Treatment of gastroschisis and omphalocele with biological dressings.

Porcine skin grafts and human amniotic membranes have been used as biological dressings for the treatment of gastroschisis or omphalocele in 16 newborn infants. Eleven infants with gastroschisis were managed initially by the Silastic pouch technique but delayed healing resulted in separation of the Silastic sheeting from the wound margins and required use of biologic dressings to achieve complete closure. Biological dressings were used in five patients with intact omphaloceles for all or part of their course. Average time to achieve complete closure was 55 days. Three patients died of associated anomalies. One patient developed an enteric fistula. Biologic dressings appear to be useful adjuncts in the management of some patients with gastroschisis or omphalocele.


Ouabain-sensitive adenosine triphosphatase from human kidneys.

Adenosine triphosphatase (ATPase) was studied in tissue homogenates and subcellular fractions derived from human cadaver kidneys maintained in an organ preservation unit for transplantation.  The activity of ouabain-sensitive ATPase was highest in the medulla, intermediate in the cortex and lowest in the papilla,  The cortical enzyme activity diminished with time during maintenance perfusion of the kidneys.  Similar concentrations of K+, Na+, Mg++, ATP and MgATP were required for half-maximal rates of ouabain-sensitive ATPase activity from the cortex or the medulla.  The sensitivity of the enzyme to ouabain from both parts of the kidney was similar.  K+ antagonized inhibition of the enzyme by ouabain.  Chlormerodrin, mersalyl, mercaptomerin and ethacrynic acid were inhibitors of the enzyme.


Oubain-sensitive adenosine triphosphatase from human kidneys.

Adenosine triphosphatase (ATPase) was studied in tissue homogenates and subcellular fractions derived from human cadaver kidneys maintained in an organ preservation unit for transplantation. The activity of ouabain-sensitive ATPase was highest in the medulla, intermediate in the cortex and lowest in the papilla. The cortical enzyme activity diminished with time during maintenance perfusion of the kidneys. Similar concentrations of K+, Na+, Mg++, ATP and MgATP were required for half-maximal rates of ouabain-sensitive ATPase activity from the cortex or the medulla. The sensitivity of the enzyme to ouabain from both parts of the kidney was similar. K+ antagonized inhibition of the enzyme by ouabain. Chlormerodrin, mersalyl, mercaptomerin and ethacrynic acid were inhibitors of the enzyme.


The function of the disc of the temporomandibular joint.

A study of the structure of the discs of the temporomandibular joints of three mammals showed marked differences among them. Since the animals selected had different basic patterns of mastication, it may be that each disc has become modified to different functions in different mammals.


Uterine blood flow in the pregnant rabbit.

Two methods are described for the measurement of uterine blood flow in the pregnant rabbit. The first involves the use of a Parks ultrasonic Doppler probe placed over the exposed uterine artery. The second method uses a drop counter system connected between the uterine and jugular veins. The Doppler flowmeter was used to measure uterine arterial blood flow in twenty rabbits on Day 28 or 29 of pregnancy. No significant difference was observed between blood flow on these 2 days and the absolute blood flow to one horn (plus or minus S. E.) was found to be 16.8 plus or minus 1.4 ml/min, equivalent to 27.1 plus or minus 1.8 ml/100 g tissue/min. Using the drop recorder technique, the flow to one uterine horn in eleven rabbits on Day 27 or 28 of pregnancy was 12.5 plus or minus 1.9 ml/min, equivalent to 23.6 plus or minus 3.2 ml/100 g tissue/min. The pressure-flow relationship in the uterine vascular bed was studied using the Doppler flowmeter and graded mechanical occlusion of the arterial supply. Within the range of pressures studied, the flow was found to be linearly related to the arterio-venous pressure difference. This suggests that the uterine vascular bed was fully dilated under the conditions of study.


Transfection of Escherichia coli spheroplasts. V. Activity of recBC nuclease in rec+ and rec minus spheroplasts measured with different forms of bacteriophage DNA.

The in vivo activity of the recBC nuclease was assayed by transfection of isogenic rec+ and rec minus spheroplasts with bacteriophage DNA of various origin and structure. The results indicate that the recBC nuclease can limit transfection at several stages during the production of an infective center; such limitations depend primarily on whether the DNA is in, or assumes, a nuclease-sensitive structure. The first stage of limitation can occur when a nuclease-sensitive transfecting molecule enters the spheroplast. Other potential limitation points occur during replication and maturation of the bacteriophage DNA. The initial stage can be bypassed by using recBC nuclease-resistant molecules such as circular forms. Through analysis of results with other DNA structures, we found that in vivo the effects of the double-strand exonucleolytic activity of the recBC nuclease predominated. The effects of the single-strand nuclease activities seem to be modified from those observed for the purified enzyme in vitro (Karu et al., 1974). Inside the cell, the single-strand exonuclease activity is very weak and the single-strand endonuclease activity is abolished almost completely.


Anterior transposition of urethra.

The case reports of 3 patients who underwent anterior transposition of the urethra are presented. Our modification is believed to shorten the operative procedure and to be equally satisfactory compared to the results presented by previous urologic surgeons. We join those who recommend this operation in the thin female patient who has a neurogenic bladder with constant leakage around the indwelling urethral catheter despite use of larger size tubes.


Retroperitoneal germ cell tumors with no apparent testicular involvement.

Five men with retroperitoneal germ cell tumors and no apparent testicular involvement are described. Each case has a different feature lending support to one of the various theories concerning the origin of these tumors. Patients with such a tumor are best managed without removal or biopsy of either testis. Careful, periodic re-examination of both testes is suggested. Only if a testis subsequently becomes abnormal is its removal indicated.


Vectorcardiographic findings in concentric and eccentric left ventricular hypertrophy as determined by angiocardiograms. 1. Preliminary report.

In forty-one patients with various heart diseases including 29 with LVH, the vectorcardiograms of Frank system and angiocardiographic findings correlated minutely. Based on the left ventricular wall thickness in end-diastole, left ventricular end-diastolic volume, and the length of the long axis of the left ventricle obtained in angiocardiograms, typical left ventricular hypertrophy was classified into types 1a, 1b, 2a, 2b anatomically. The vectorcardiograms in these 4 types represented different patterns with regard to the QRS and T loops respectively. The QRS voltage in the left ventricular hypertrophy closely correlated to the left ventricular wall thickness in end-diastole, the left ventricular end-diastolic volume, and the left ventricular mass. Marked ST and T changes in the left ventricular concentric hypertrophy characterized by increase in wall thickness without definite chamber enlargement may be closely related to the abnormal muscle state with the increased left ventricular wall thickness, the probably due to relative hypoxia in origin. The Q loop of patients with severe left ventricular concentric hypertrophy was definitely differentiated from that of most patients with the pure left ventricular eccentric hypertrophy which was characterized by chamber enlargement with usually slight thickening of the wall. A possible mechanism regarding inconspicuous or prominent Q loops in both concentric and eccentric LVH was presented. An important factor of the delay of the time of occurrence of the spatial R vector in the left ventricular eccentric hypertrophy is the greater distance of the intraventricular conducting pathways caused by the left ventricular dilatation. By means of assessing the vectorcardiogram of the left ventricular hypertrophy, relatively exact anatomy of the left ventricular hypertrophy can be determined.


[Catecholamine in the myocardium; a fluorescence histochemical study].

There has been many studies on myocardial catecholamine (CA) in congestive heart failure and ishemias heart disease. However, it has been mainly studied pharmacologically and biochemically and has not been elucidated completely the local change of CA of the myocardium. CA in sympathetic nerves was first stained fluorescence histochemically by Falck-Hillarp in 1962, and many observations were made on its distribution and morphologically concentration of CA in tissue was also observed. Furthermore, the fluorescence histochemical simplified method (cryostat method) by Laties and Jacobowitz was published in 1967. This cryostat method produced the same good preparation instead of the freezed dried method of Falck-Hillarp and could be used semi-quantitatively for the determination of CA concentration in tissue. The author examined fluorescent-histochemically the distribution of CA in sympathetic nerve endings of the myocardium of animals (mouses, rabbits and dogs). After the administration of several agents and in some pathologic conditions, those were in the hypertrophied heart and impending heart failure, in myocardial infarction and A-V block. Furthermore, the change of CA in the myocardium was examined biochemically by von Euler method and its results were compared with the results of fluorescence-histo chemical method.


Effect of serotonin depletion on the central regulation of the carotid sinus reflex in rats.

Effect of serotonin depletion in the rat brain on the sympathetic pressor response to occlusion of the common carotid arteries was examined along with the sequential transection of the brain stem. In rats with the brain serotonin depleted below 10% of control by p-chlorophenylalanine, the reflex pressor response significantly decreased, but the reflex sensitivity was unchanged in any transection regimen, suggesting the decrease originated in the associated hypertension; The infracollicular transection augmented the reflex reaction and sensitivity in both groups, and the medullospinal separation abolished the reflex; It is concluded that the brain serotonin would not be significantly involved in the central regulation of the sympathetic component of the carotid sinus reflex, and that the structure rostral to the midbrain could play an inhibitory role in the integrative regulation.


Rb86 uptake of various organs of the spontaneously hypertensive rats: (a preliminary note).

Twenty spontaneously hypertensive rats (SHR) and 20 control rats were used for measurements of Rb86 uptake of various organs. Hemodynamic measurements and the heart weight to body weight ratio showed a significant and sustained hypertension and increased heart rate in SHR; Ratio of Rb86 uptake in the kidney, brain, liver, adrenal gland, pancreas, and spleen to that in RV was smaller in SHR than that in the control rats. The ratio of Rb86 uptake of inner layer to outer layer of LV, which represents distribution of blood flow to the endocardial layer and epicardial layer, was not different between SHR and the control rats. The fraction of regional flow in the outer and inner cortex, juxtamedulla, and medulla of the kidney was not different between SHR and the control. The present preliminary study may suggest that myocardial blood flow in SHR is greater than that in the control rats. The relationship between cardiac hypertrophy and myocardial flow was discussed.


Non-uniform myocardial blood flow caused by stellate ganglion stimulation.

The blood flow through the anterior wall of the left ventricle has been studied during electrical stimulation of the left stellate ganglion of anesthetized dogs. The flow was continuously monitored by heated cross-thermocuple. Ganglion stimulation caused a significant increase in the flow through the outer half while producing relative ischemia of the inner half of the wall. Pretreatment with propranolol reduced regional difference of flow changes. Significantly augmented non-uniform flow changes, however, were produced by ganglion stimulation during hypertension caused by aortic constriction or by methoxamine. The results indicate non-uniform blood flow distribution which can be produced by sympathetic nerve excitation.


Cardiac hypertrophy in spontaneously hypertensive rats.

The energy metabolism of cardiac hypertrophy in spontaneously hypertensive rats (SHR) was studied chronologically by histochemical and in part chemical methods. The activities of various enzymes, such as glucose-6-phosphate dehydrogenase (G6PDH), lactate dehydrogenase (LDH), isocitrate dehydrogenase, succinate dehydrogenase, beta-hydroxybutylate dehydrogenase (beta-HBDH) and monoamine oxidase (MAO) in the cardiac muscle were determined histochemically. beta-HBDH activity was greatly increased in the stage of developing hypertension in SHR. LDH activity increased simultaneously with the rise of beta-HBDH activity. Moreover, MAO activity increased markedly in later stages when the blood pressure was already elevated in SHR. To confirm the histochemical findings of beta-HBDH activity, the mitochondrial fraction of cardiac muscle was subjected to chemical assay. The chemical findings of myocardial beta-HBDH in SHR corresponded well with the histochemical findings. The myocardial beta-HBDH activity in SHR increased markedly at the age of 5 to 9 weeks, while no or minimal activity was found in controls of the same age. No significant difference of beta-HBDH activity was observed between SHR and controls in the mitochondrial fraction from the diaphragm and liver. The increase of beta-HBDH activity in the cardiac muscle of SHR prior to the development of cardiac hypertrophy suggests that the metabolism of ketone bodies may play an important role in providing the energy necessary for the development of cardiac hypertrophy in SHR.


Coronary artery anomalies in patients with tetralogy of Fallot.

A left anterior descending coronary artery arising from the right coronary artery can be easily injured during performance of a right ventriculotomy for correction of tetralogy of Fallot. This occurred in 2 of the 23 patients in this series, and both patients died from myocardial failure in the early period after operation. Of 19 patients who presented a combination of tetralogy of Fallot and unusual coronary artery distribution, injury to the abnormal coronary artery was avoided by a transverse right ventriculotomy either alone or combined with an upper vertical incision in 17 patients. In 2 patients a Dacron tube graft was inserted between the right ventricular outflow tract and the pulmonary artery. In 2 patients a right ventriculotomy was avoided by closing the ventricular septal defect through a transaortic approach. All 21 patients survived. Before a vertical or longitudinal incision in the right ventricular outflow tract is performed, the coronary artery distribution should always be checked and confirmation made of the normal origin of the left anterior descending branch from the left coronary artery to the left of the pulmonary artery.


Tetralogy of Fallot with atresia of the left pulmonary artery: surgical repair using a homograft aortic valve.

Two cases of tetralogy of Fallot with unilateral absence of the left pulmonary artery are presented. Both patients required a valve-retaining homograft because of severe pulmonary valve incompetence following previous surgical correction. This uncommon anatomic variant presents special surgical problems, as pointed out in a review of the literature.


Congenital and acquired abnormalities observed in live-born and stillborn neonates.

This report records the congenital and acquired abnormalities observed during the first 4 days of life in 21,142 live-born infants. Gross abnormalities observed in 300 stillborns also are recorded. The abnormalities are those thought to be of clinical or possibly clinical significance. Also included are other conditions ordinarily not considered to be a congenital abnormality, such as convulsions. Definitions are given when indicated. The incidence rates per 1,000 births for specific malformation noted in the first 4 days of life are provided for all births, for live births, for live births under 2,500 g, and for stillbirths. The need for accurate studies of specific forms of congenital malformations is reiterated. The rate for all malformations combined is not given since it is difficult to interpret or use for comparisons because of variations in the definition of malformation and in completeness of ascertainment in different studies.


Renal cell carcinoma.

The natural history, presenting signs and symptoms, and radiologic evaluation of patients with hypernephroma are reviewed. Radical nephrectomy is the treatment of choice in patients free of metastatic disease. Patients who have evidence of metastatic disease should not be subjected to nephrectomy unless hemorrhage, pain, or some other severe local problem warrants it. Radiotherapy and chemotherapy may be useful as adjunctive therapy in a patient with metastatic disease.


[The inhibition of various bacterial proteinases with natural proteinase inhibitiors(author's transl)].

Proteus mirabilis, citrobacter intermedius, staphylococcus aureus haemolyticus and staphylococcus albus produce extracellualr proteinases with maximum activity at pH 7.8. These proteinases are inhibited practically completely by human and animal blood serum. This inhibitory activity of human serum is caused by alpha2-macroglobulin. Ovomucoid showed nearly the same inhibitory activity as alpha2-macroglobulin.


[Simultaneous estimation of flow rates, electrolyte and proteinconcentration and discelectrophoretic separation of fractionated human parotid saliva(author's transl)].

Fractionated human parotid saliva from normal persons was separated by column-acryamid-gel discelectrophoresis. Flow rates, electrolyte-concentrations and total protein content of the stimulated and unstimulated parotid-secretion were determined simultaneously. Significant patterns of proteincomposition were found for stimulated and unstimulated parotid saliva. Most typical changes of protein bands were found in the anodal near gel region, within a group of four bands, called by us f, g, h and i. In the cathodal near gel region as well significant changes in the bands a, b, c and d were found; by glycoprotein staining these bands showed good staining.


[Electron microscopic screening of plastics and rubbers used for implantation(author's transl)].

Results are reported of electron microscopic screening tests investigating the biostability of plastics and rubbers used as implantation material. The layers which generally appear on the surface of the inlay are described and their significance in the demarcation of the organism against the foreign body is discussed.


[100 Years of laryngectomy (author's transl)].

Since the first laryngectomy was performed in 1873 by Billroth in Vienna, this method has been continually further improved. A horizontal laryngectomy with preservation of the air passages was performed in 1957 by Majer and Rieder and named cricohyoidopexy. Cricohyoidopexy consists basically of the removal of the thyroid cartilage and the soft laryngeal tissues prior to pulling the preserved cricoid cartilage upwards and fixing it to the epiglottis and the hyoid bone. This operation ensures that the air passages, the voice, and deglutition are preserved. Serafini and Arsian have extended this technique to a tracheohyoidopexy, which has been successfully performed in many cases. Certain aspects posing problems and creating difficulties during these operative procedures, such as respiration, deglutition and the voice are discussed. These methods of functional laryngectomy, however, have only a limited indication.


[Osteoplastic epitympanotomy and the pathology of the middle ear. Part 2: The microstructures of the epitympanum and their significance concerning the pathology of the retrotympanal spaces (author's transl)].

The two goals of osteoplastic trepanation of the middle ear spaces are first a direct inspection of the main areas of pathologies within the epitympanum and secondly a better understanding of the infected middle ear diseases through careful preparation and exposure of the pathologic processes. A new way of approval could be found by taking into account the anatomical and topographical realities and the possible deviations form normal cases. This opens a better understanding of all those variations. Without touching the microstructures of the tympanum their inspection and preparations are hereby made possible macro- and microscopically. This leads to the conclusion that the tympanic structures are involved in the formation and progression of infected middle ear diseases. The correlation of the "aeration pathways" and the "drainage outlets" of the middle ear as an interdepending functional unit can be seen by this new intrasurgical inspection-based on light- and electronic microscopic research of various authors-as well as through the fact that middle ear mucous membrane is a truly respiratory membrane with no difference to other aeration pathways as found in the nose. A of a summation of mucous membranes in the area of the diaphragma is that minor catarrhal inflammations will block this aeration pathway of the middle ear. At the same time an open tuba auditiva can be found in acute, subacute and chronic middle ear diseases. Our findings that the ventilation of the ear is in most cases blocked at the diaphragma and not at the tube leads to questions on the one hand regarding the function of diaphragma and to the opinion on the other that the ventilation system of the middle ear is divided in two sections by the diaphragma: An anterior section including tuba and hypomesotympanon and a posterior including epitympanon, aditus, antrum and the pneumatic cells of mastoid and pyramid. The anterior section still is ventilated through the tuba when blocked at the diaphragma, in the posterior one ventilation and drainage are blocked even by mildly infected processes. Longer lasting infections have severe consequences for these spaces and the tympanic membrane.


[The clinical application of neuronography in facial palsy(author's transl)].

Neuronography is the method chosen for early diagnosis in facial palsy, since it best suits the facts of pathophysiology. After presentation of the stages of nerval damage in facial palsy and its corresponding results of neuronography the paper deals with the prognostic conclusions.


[Current remarks for use of the TNM classification on head and neck (author's transl)].

The revised rules of classifications of UICC (1973) for the field trail 1974-1977 will be published (nasopharynx, oropharynx, hypoparynx; larynx; oral cavity); own recommendations for the organs inner nose and sinuses, salivary glands and skin (head and neck) are added. In the enlarged TMN-key identification number, date of diagnosis, number of localisation, symbol c (certainty) and number of histology are mainly taken into consideration; stage and staging remain secondary. Checklists and proformas prepared for use in a computer simplify the documentation.


[Assessment of hearing losses using diagrammatic curves (author's transl)].

Diagrams are given to facilitate the assessment of hearing losses and make it more flexible. These indicate the degree of deafness derived from the results of various test procedures and the MdE of the degree of deafness of both ears. It is suggested that "degree of deafness" be used instead of the "percentage hearing loss".


[The effect of various antibiotics on the mixed flora of the maxillary sinus in sinusitis(author's transl)].

The effect of four frequently used antibiotics on the germs of the sinus maxillaris was studied. For this purpose germs of the sinus max. rinsing fluid, got from 127 patients, were cultured under nearly the same physical and chemical conditions which can be expected in the sinus itself. Each antibiotic substance was studied with three different comcentrations in the culture medium. By extrapolation of the linear regression between some characteristical parameters of the culture absorbancy development and the concentration, the inhibitory concentration can be estimated. The efficacy decreases in the following order: Doxycyclin greater than Gentamycin greater than Ampicillin greater than Lincomycin. An inhibitory concentration results, if the antibiotics are instilled in the sinus itself. The general side effects can be neglected but not at all the local ones. Investigations in this direction are still going on. As a preliminary report, 700 instillations of Lincomycin turned out with no incident.


[Hepatic scintigraphy and laparoscopy in the diagnosis of the metastatic liver neoplasms. Comparative studies in 112 cases].

Personal experience of hepatic scintigraphy and laparoscopy in the diagnosis of secondary tumors of the liver is reported. The usefulness of both the techniques, associated, is proved by the small number of cases (2,98%) where metastases remained undiagnosed before surgery. Considering only the results of scanning, a larger number of "false positive" is noted, while those of laparoscopy are more often "false negative".


Paired moving charges in mitochondrial energy coupling. II. Universality of the principles for energy coupling in biological systems.

The thesis is developed that an acceptable model of biological energy coupling must have universal application. The paired moving charge model of mitochondrial energy coupling is examined from the standpoint of this thesis. Fundamental to this model is the notion that energy coupling involves interaction between paired uncompensated charged species in two vectorially aligned and spatially separated reaction centers. The two charge-separating devices are assumed to be the electron transfer chain (in chloroplast and mitochondria) and intrinsic ionophores (in all transducing organelles and kinases). The universality of the ionophore principle becomes then the crucial test of the validity of the paired moving charge model. The multiple facets of ionophore-mediated couples processes are explored, e.g., coupled hydrolysis of ATP, hormonal control of ion movements, and active transport.


Correlated suppression by 5-bromodeoxyuridine of tumorigenicity and plasminogen activator in mouse melanoma cells.

The decrease of tumorigenicity by mouse melanoma clone B559 after growth in the presence of 5-bromodeoxyuridine (BrdU) has been correlated with a decrease in detectable cellular plasminogen activator. Reduction of both activities occurs after one to two cell divisions in the presence of this thymidine analog and is virtually complete within three to four cell cycles. These changes are fully reversible; four to five cell divisions in the absence of BrdU are sufficient to allow both tumorigenicity and plasminogen activator levels to return to normal. These results support the hypotheses that (a) the expression of a cellular plasminogen activator is closely associated with the transformation of normal to malignant cells and that (b) the suppression of tumorigenicity by BrdU reflects the capacity of this base analog to inhibit the expression of specialized functions which accompany the malignant state.


The problem of sampling homologous groups of nephrons during development of the chick mesonephros.

With the aim of defining homologous groups of nephrons in the chick mesonephros at different stages of development, we opened the abdominal wall of 295 White Leghorn embryos at stage HH 26 and marked off 6 segments of equal length at different levels of the organ by Seichert's plastic linear marking method (Seichert 1965), using marks previously introduced into the vertebral column at the same levels as a guide. The embryos were removed after 2-6 days, weighed and classified according to weight. The primordia of the marked vertebrae were identified. The length of the artificially defined segments or their relationships to both poles of the mesonephros were evaluated in projections. The portion of the mesonephros above Th 3 level shorten during the period of observation, while the more caudal segments grow in a craniocaudal gradient. Homologous groups of nephrons can be identified only by the marking technique, except for those at Th 7 level, whose distance from the caudal pole does not alter up to the 11th embryonic day.


Inflation reflex in the rat.

The Breuer-Hering inflation reflex [BHIR] was elicited in conscious and anaesthetized rats by inflating the lungs with constant pressures of 5--20 cm H2O. The reflex was elicited well in conscious animals, but even with the maximum stimulus [inflation of 20 cm H2O, corresponding to about 4.5-fold the tidal volume] the duration of apnoea did not exceed 4 control respiration cycles. In anaesthetized animals, the same stimulus let to apnoea lasting 180--400 control respiration cycles on the average, according to the type and depth of general anaesthesia. The duration of apnoea in occlusion of the air passages in the expiratory position increased with the depth of anaesthesia, while in occlusion of the air passages at the peak of inspiration it was shortened. Stimulation of chemoreceptors [inhalation of a mixture 4% CO2 in O2 or of 8% O2 in N2] did not influence the elicitability or duration of the BHIR, nor did cooling the rats to 28 degrees C or heating them to 38 degrees C. The mean respiration frequency was 98 c/min in unanaesthetized rats, 96 c/min in urethane anaesthesis and 79--48 c/min in halothane anaesthesia, according to the depth of anaesthesia. Bilateral cervical vagotomy reduced mean respiration frequency to 35.6 c/min in conscious rats and to 31 c/min in urethane-anaesthetized animals. The results indicate the existence of species-related differences between basic regulatory mechanisms in the rat and certain other mammals.


Participation of the Breuer-Hering inflation reflex in regulation of respiration frequency in anaesthetized rats.

The respiration frequency and Breuer-Hering inflation reflex (BHIR) values were compared in anaesthetized rats after unilateral vagotomy. Nos significant differences were found in the decrease in respiration frequency after transection of the right of left vagus and there were no differences in BHIR values in correlation to conduction by the right or left vagus. With unilateral vagotomy and an inflation pressure of 20 cm  H20 the BHIR values fell to about one fourth of the control values. Progressive cooling of the contralateral vagus led at 8-10 degrees C to a non-significant decrease in respiration frequency to 87% of the initial value; in this state the BHIR could not be elicited. Further cooling of the vagus to 0 degrees C reduced respiration frequency to the same values as in bilateral vagotomy. The discrepancy between the mild decrease in respiration frequency and simultaneous disappearance of the BHIR shows that changes in respiration frequency in anaesthetized rats are not directly correlated to the presence of the BHIR.


The inhibitory action of the light meromyosin component on the myofibrillar and actomyosin atp-ase.

The protein component of light meromyosin [LMM-1] was shown earlier to relax glycerinated muscle fibres and actomyosin. Presently its influence on ATP-ase activity of myofibrils, actomyosin, myosin and heavy meromyosin has been studied. LMM-1 decreases Mg-ATP-ase activity of myofibrils and of reconstructed actomyosin by 25-- 30% and does not change [or slightly increases] Ca-ATP-ase activity of this protein and of myosin; besides LMM-1 is able to increase Mg-ATP-ase of HMM substantially. LMM-1 markedly inhibits [preliminary data] the activation of ATP-ase activity of HMM by actin. It is suggested that LMM-1 protein interacts with myosin and decreases the actin-myosin affinity, displacing actin out of the complex. It reacts only with one of the heads of myosin. Probably this suggestion can account for a relatively slight inhibition of ATP-ase activity of complex by LMM-1. LMM-1 represents a natural and specific inhibitor of Mg-AM-ATP-ase activity, included in the structure of myosin protofibrils and interacting with the myosin active site region.


Macromolecular turnover in mice (C57BL times C3H) liver, thymus and kidney after partial hepatectomy.

Studies have been presented concerning the definition of bioassay systems, in terms of macromolecular kinetics as it pertains in advance to ENU carciogenic sensitivity. Male mice (C57BL female times C3H male) 6 weeks of age were partially hepatectomized and labelled with thymidine 3-H, uridine 3-H and leucine 3-H as precursors for DNA, RNA and protein synthesis respectively. Specific activity of all these three parameters of liver, thymus and kidney were followed for 5 days at regular intervals, and for 6 weeks at randomly chosen intervals. The goal of this study which we obtained, is a three-phased curve in liver for each macromolecule studied; RNA synthesis reached its first peak 18 hours, protein synthesis 24 hours, and DNA synthesis 30 hours after partial hepatectomy. Synthetic macromolecular turnover in other organs (thymus, lung, kidney, brain) were not affected in a similar way, inspite expecting some factors of a humoral nature. An accurate knowledge of the timing in macromolecular synthesis after partial hepatectomy in mice is an essential preliminary study for the development and definition of a model protocol for ENU--single dose having approximately 10-15 minutes half-life carcinogenic response.


Detection of small vessels for microsurgery by a Doppler flowmeter.

The Doppler flowmeter saved time and helped us to quickly find the exact position of the donor and the recipient vessels in the microvascular transfer of a free deltopectoral flap to the face.


Transverse abdominal flaps and the deep epigastric arcade.

Further experience with the transverse abdominal flap, based on the deep epigastric arcade, is described. This flap is a logical extension of the concept of the deltopectoral flap (based on the internal mammary). The transverse abdominal flap derives its blood supply from the perforating branches of the deep epigastric arcade, and it can be used  without a delay procedure when so constructed.


The effects of diagnostic X-ray exposure on the human fetus: an examination of the evidence.

Epidemiological studies have demonstrated an increased incidence of morbidity and mortality among children exposed prenatally or preconceptually to diagnostic x-rays, as compared to nonirradiated controls. In those studies radiation exposure occurred on a selective basis, as the examination was always medically indicated. Comparisons of those studies and comparable ones in which radiation exposure occurred on a nonselective basis (from routine pelvimetry examinations or atomic bomb radiation) indicate that the latter studies do not confirm the former and a significant discrepancy is present in each instance. Thus, some doubt is cast on the validity of the former studies.


Immunoglobulin-positive cells: their appearance in the mixed lymphocyte reaction.

In mixed lymphocyte cultures prepared with thoracic duct lymphocytes from allogeneic rats, approximately 20 percent of all blast cells that appeared at the end of 72 hours of incubation had surface receptors for rabbit antibody to rat immunoglobulin.


Echocardiographic and electrocardiographic criteria for diagnosing left atrial enlargement.

Electrocardiographic criteria for left atrial enlargement (LAE) were evaluated in a group of 100 patients with a wide spectrum of cardiovascular diseases and compared with the echocardiographic measurement of left atrial dimension (LAD). Data analysis showed a high degree of correlation between the echocardiographic measurement of LAD and the EKG criteria for LAE. The magnitude of the P terminal force in lead V1 was the most specific of the EKG criteria evaluated, while the P/P-R segment ratio was least specific. Concordance between the two methods of measuring left atrial size increased when multiple positive EKG criteria were present.


Lumbar fusion using facet inlay grafts.

A long-term analysis of 106 patients who had lumbar fusions between 1959 and 1969 is reported. The method used in this series was an inlay bone graft pointed at each end and beveled at its cephalic portion to permit easier insertion. The sacroiliac ligaments are not disturbed while obtaining the bone graft and no sacroiliac complications have occurred. The necessity for determining whether any psychophysiologic symptoms exist before a spinal fusion is emphasized. This study found the inlay facet technic of spinal fusion to be a worthwhile procedure in properly selected cases of low back and leg pain.


Problems with an electromagnetic blood flowmeter.

Recurrent unexplained interference and day-to-day variation were encountered during preliminary studies with a sine-wave electromagnetic flowmeter. Using in vitro techniques, contributory causes were found to be defective leads to the flowmeter cuffs, inadequate contact between cuff and vessel, and failure to use an earth lead. When these faults were corrected, a study was made of the effects of haematocrit, temperature and the comparison of blood vessel or dialysis tubing in vitro. Final in vivo confirmation of the validity of the cuff was obtained by comparison with a cannula probe.


Technical improvements in the management of omphalocele and gastroschisis.

1. Omphalocele and gastroschisis carried a poor prognosis (50 per cent survival) until the last half decade. 2. The use of a temporary prosthetic covering  for the exposed viscera has strikingly altered the outlook in these conditions. 3. Ventilatory assistance, when required, and the ability to monitor blood gases have contributed also to the improved survival rates. 4. In gastroschisis the capability of giving total intravenous nutrition has allowed survival through the long period of bowel dysfunction common in the postoperative period.


Body sculpturing.

Significant improvements in body contour can be accomplished by surgical procedures having reliable, predictable results. Similar to the modern sculptor of inanimate art forms, plastic surgeons have utilized new materials and devised new techniques to achieve aesthetic improvement of the face, trunk, and extremities. The goals of the surgical sculptor are perhaps more challenging than those of the pure artistic sculptor, not only because they must result in improved appearance but also because the surgeon is limited at all times by considerations of regional anatomy, the availability of viable tissue materials, and the safety of his patient.


Septate junctions in the calcareous sponge Sycon ciliatum.

Most cell junctions of Sycon are of the simple kind in which the plasma membranes are separated by an intercellular space of about 15 mmu. True septate junctions are found between sclerocytes. They are similar to those of coelenterates and echinoderms, with a parallel arrangement of septa as seen in tangential sections. The functional implications of the restriction of this type of junction to the sclerocytes are discussed.


The aglomerular nephron of antarctic teleosts: a light and electron microscopic study.

Complete serial sections demonstrated that ten species of Antarctic teleost fishes representing two families had aglomerular kidneys. The aglomerular nephron of such kidneys consists of two distinct regions: (1) a highly contorted principal segment and (2) a system of collecting tubules and ducts. Throughout the principal segment the cells are characterized by densely packed microbilli and a single cilium projecting into the lumen. Within the cytoplasm, lysosomes are rarely encountered, as would be expected if there is little or no reabsorption of protein from the urine. At the base of these cells, the plasma membrane is prominently infolded in close association with abundant mitochondria. The overall fine structure of the principal segment cells is consistent with their probable function in the secretion of ions into the formative urine. Between the principal segment and the collecting tubule is a very short transitional zone characterized by transitional mucus cells and multiciliated cells. The collecting tubule and duct system is lined entirely by mucus cells. In comparison with principal segment cells, the mucus cells have a well-developed Golgi complex and abundant secretory granules in the apical cytoplasm; these granules presumably contain the non-sulfated acid mucopolysaccharide demonstrable by light microscopic histochemistry.


Preparation and antigenic properties of androsterone-7-BSA conjugate.

The 7-carboxymethoximino derivative of androsterone (1) has been prepared from dehydroisoandrosterone-17-ethyleneketal by a sequence involving inversion at C-3, introduction of a carbonyl at C-7, and reduction of the double bond at C-5. The substance was condensed with BSA by the carbodiimide procedure to afford a conjugate which produced anti-androsterone antiserum in innoculated rabbits. The antiserum is sufficiently active to be useful in radioimmunoassay procedures.


One-way nonstimulation of mixed leukocyte culture in dog families.

Fifteen dog families were studied in mixed leukocyte culture.  In eight families of seven different breeds, one-way nonstimulation in mixed leukocyte culture was observed.  This could be explained by lymphocyte-defined (LD) homozygosity in most instances.  In one family, an inclusion phenomenon was postulated, and in another, a deletion.  LD homozygotes can serve as reference for LD typing and can also help elucidate the relative role of the LD locus for transplantation of organs.


Atypical mixed lymphocyte culture.  Identity between mother and child in leukemia and aplastic anemia.

The mixed lymphocyte culture tests between one patient with acute lymphocytic leukemia and her mother and between another patient with aplastic anemia and his mother were found nonreactive, despite a one-haplotype difference for HL-A.  Two crossovers in each family at the MLC locus or a specific defect in lymphocyte responsiveness could be possibly explantations.  The mother of each patient could be considered a potential donor for bone marrow transplantation.


Effects of intravenous methylprednisolone on mixed lymphocyte cultures in normal humans.

Mixed-lymphocyte-culture response and peripheral lymphocyte counts were determined after 100 mg and 1,000 mg of methylprednisolone were administered intravenously to healthy volunteers; The MLC response was significantly suppressed in both groups for at least 12 hr. The degree of suppression of the MLC response did not differ between the two groups. Lymphocytopenia persisted for at least 24 hr. The MLC response, however, returned to its full capacity within 24 hr. In the low-dose group this response showed a marked rebound phenomenon at 24 hr. These findings indicate that methylprednisolone has a profound inhibitory effect on lymphoid cells' response to allogenic stumli in the MLC system.


[Comparative karyological study of lizards of family Agamidae. II. Karyotypes of 5 species of the genus Agama].

Chromosome complements of the following species were described: Agama sanguinolenta Pallas, 1813; A. caucasica Eichwald, 1813; A. erythrogastra Nikolsky, 1896; A. lehmanni Nikolsky, 1896; and A. hymalayana Steindachner, 1867. Agama sanguinolenta has 46 chromosomes, all of them being telocentric. The remaining 4 species show 2-n equal to 36:6 pairs of meta- or submetacentric macrochromosomes and 24 microchromosomes. Sex chromosomes have not been found. Possilbe evolutionary interpretation of a profound karyologic divergence in the genus Agama and karyotypic relationships of Agamidae with Iguanidae of the New World, are discussed.


Classification of incontinence.

A clinical definition of incontinence and a clinical classification of its various forms is offered for consideration. The classification is part of a wider classification of handicaps being prepared to supplement existing classifications of diseases and disorders classified according to aetiology, systems, and anatomy. Nine handicaps (locomotor, visceral, visual, communication, intellectual, emotional, invisible, and "other") are distinguished. Incontinence is classified as a "disorder of excretion, which is itself one of four divisions of visceral handicap'.


[Errors in the diagnosis of ruptures of the straight muscle of the abdomen].

Based on study of the clinical picture of ruptures of straight abdominal muslces in 9 patients, it is considered that this pathology is considered to occur in males as frequently as in females, a spontaneous rupture being observed more frequently in females over 40 years of age, who had multiple deliveries previously and show arterial hypertension. The man signs of spontaneous or traumatic rupture of straight muscles are as follows: a sudden onset of pains conditioned by hematoma, pressure on the parietal peritoneum, in palpation a detection of tumor in the tumor in the region of m. rectus abdomins that would not disappear in abdominal tension; and also intensification of pains in the hematoma region in elevating the head in a supine position. As a rule, the body temperature is normal, but the leucocyte count may be somewhat increased. Usually, such patients are treated conservatively. Surgical intervention seems to be indicated only in organization of hematoma or its suppuration.