A clinical evaluation of postoperative alkaline reflux gastritis. Alkaline reflux gastritis is by far most common following gastric operations, but its true incidence remains to be determined. It is a distinct postgastrectomy disorder with unique features from other postgastrectomy syndromes. Eight patients with the diagnosis of postoperative alkaline reflux gastritis are presented. Five patients had Henley jejunal loop interposition procedures and two had takedown of their gastroenterostomy and pyloroplasty. One patient had a Roux-en-Y jejunojejunostomy after a vagotomy and pyloroplasty. A Henley jejunal loop failed to relieve the symptoms in one patient and a Roux-en-Y jejunojejunostomy brought complete relief of symptoms. Six of the eight patients had esophagitis. The frequent coexistence of alkaline esophagitis and alkaline gastritis must be considered in both treatment.


Surgical management of strictures of the lower thoracic esophagus. An obstructing lesion of the lower thoracic esophagus should be evaluated carefully and appropriate surgical therapy planned to correct the abnormal physiology. Gastroesophageal reflux is the most frequent cause of esophageal stricture and usually can be managed effectively by dilatation of the esophagus, restoration of a competent lower esophageal sphincter, and repair of an associated hiatal hernia. Collis gastroplasty and a Belsey herniorrhaphy are useful when the esophagus is excessively shortened. Firm, fixed esophageal strictures may be treated by the Thal procedure accompanied by Nissen's fundoplication or by resection of the stricture and interposition of a colon graft or an achlorhydric tube. The management of other benign strictures secondary to scleroderma, ingestion of caustic substances, or benign neoplasms must be individualized. Most benign strictures may be cared for by dilatation; however, firm, fixed strictures should be resected. Wide surgical resection is indicated for primary malignant lesions of the lower thoracic esophagus that are localized or have limited lymph node metastasis.


Diaphragmatic hernia caused by trauma: experience with 35 cases. Traumatic diaphragmatic hernia often is not recognized after the initial injury. Early recognition of this entity is of utmost importance since obstruction, strangulation, hemorrhage, viscus perforation, pleural fistula and empyema may occur at any time following the diaphragmatic disruption. A high index of suspicion, history of previous thoracoabdominal trauma, physical examination of the chest and roentgenographic evidence should aid in early and definitive diagnosis. Right-sided herniation should be considered in the differential diagnosis of masses about the right lower lung or diaphragm. Bilateral ruptures may also be encountered. Operation should be performed as soon as the diagnosis is made. In general, transabdominal route should be used in acute ruptures while chronic herniation should be approached through the chest.


Hemodynamics of experimental portal venous occlusion in dogs. The effects of graded occlusion of the portal vein upon hepatic arterial blood flow were studied in anesthetized dogs to evaluate the so-called "reciprocal relationship" between portal venous flow and hepatic arterial flow in maintaining oxygenation of the liver. An obstruction that increased portal venous pressure to 20 mm Hg was accompanied by a transient increase in hepatic arterial blood flow without changing the other hemodynamic parameters. Release of portal venous occlusion was accompanied by a transient fall in hepatic arterial blood flow in this group of experiments. Increasing portal venous pressure to 30 mm Hg caused a gradual but progressive fall in arterial pressure accompanied by a significant fall in hepatic arterial blood flow. With complete obstruction of the portal vein there is a reduction in arterial pressure to the same level of portal venous pressure and a significant and sustained diminution in hepatic arterial blood flow. These observations conflict with previously described theories of a relationship between diminution in portal venous flow and increases in hepatic arterial blood flow.


Surgical trauma and pericardial fibrinolytic activity. Fibrinolytic activator activity was identified in canine pericardium by fibrin slide and fibrin slide and fibrin plate techniques and shown to be sighnificantly decreased following trauma.  Cotton sponge abrasion, heating, drying and use of electrocautery and DC electro-shock significantly decreased pericardial fibrolytic activity.  Operative decreases in pericardial fibrinolytic activator activity may be significant in the etiology of postoperative pericardial adhesions and constrictive pericardial syndromes.


Presacral teratoma in the adult.

Presacral teratoma in the adult. Sacrococcygeal teratomas are unusual tumors in children, and are extremely rare in adults.  A review of the literature has revealed 69 reported cases of presacral teratomas in adults, and an additional two cases are presented, one in association with a meningocoele.  Surgical excision is the treatment of choice.  Malignant changes were noted in 11 per cent of cases.


Carotid endarterectomy under regional anesthesia. Regional anesthesia generally has been satisfactory in performing carotid endarterectomy as reviewed in a previous five-year experience from Walter Reed Army Medical Center. The results are comparable to other reported series with no operating room deaths, an overall operative mortality of 2.6 per cent, and an incidence of transient neurological deficits of 3.0 per cent with permanent neurological deficits in 2.2 per cent.


Chylothorax complicating radical neck dissection. The third reported instance of chylothorax occurring after left radical neck dissection is presented and the literature reviewed. The pathogenesis appears to be lymphatic leakage in the neck with accumulation of chyle in the pleural space in spite of the absence of pneumothorax. The means for entry across an intact pleura is uncertain. The condition can be managed by conservative means consisting of adequate neck drainage and thoracentesis or chest tube drainage. A favorable outcome can be expected.


[Urinary tract infection in early infancy, study of 15 cases]. Urinary tract infection in the newborn shows peculiar characteristics not found in older children. 15 cases of urinary tract infection in infants aged 7 days to 2 months are presented. There is higher incidence in males (11 m./4 f.). Severe clinical picture diverse and undefined clinical course, incidence of jaundice radiological findings and posterior evolution are specially noted. Early diagnosis and effective management lined in base to evolution and prognosis. Hospital stay varied between 2 and 12 weeks. No deaths were registered.


[Pleural calcifications].

[Pleural calcifications]. Pleural fibro-hyaline calcification and plaques were noted in about 1% of chest Xrays carried out as a routine in adults. The etiological diagnosis is often difficult taking into consideration the considerable delay between the discovery of the lesion of the disease responsible. These abnormalities follow inflammatory pleural effusion affecting the visceral layer of the pleura. The autors recall certain possible complications, such as, functional disturbance, secondary infection, fistula formation and malignant change. The calcified plaques of the parietal pleura represent an excellent sign of exposure to asbestos in a population. Their characteristics, significance and mechanisms are discussed.


[HGH release after I.M. glucagon injection]. Intramuscular injection of glucagon was used to assess HGH release in 31 normal children and 4 hypopituitary dwarfs. The peak response in controls was obtained at 120 min. with values (nanograms) of 12.93 plus or minus 5.18 (p smaller than 0.0005). Values at 60 and 180 min. were equally significant when compared with basal (7.04 plus or minus 9.24, p smaller than 0.025 and 6.74 plus or minus 6.65, p smaller than 0.001). Hypopituitary dwarfs did not respond to glucagon injection.


[Natural history of urinary tract infection in children]. Urinary tract infection was studied in 61 children whose ages ranged between 6 months and 9 years. History, symptoms, urine cultures and renal function are compared between those with normal radiology and those with pyelonephritis and/or reflux and obstructive lesions. Prognosis was analized in these two groups.


[Diaphragmatic hernia in newborn].

[Diaphragmatic hernia in newborn]. Congenital diaphragmatic hernia is the object of this informative review, directed to the general pediatrician. The needs for urgent diagnosis and immediate surgical treatment are both stressed. Aside its embriological, clinical, and diagnostic aspects other important areas are dealt with, such as associated malformations and surgical treatment. Special points are made regarding pre and postoperative care, including pitfalls in surgical treatment due to crowding of the abdomen under severe pressure.


[Generalized lipodistrophy (Berardinelli-Seip syndrome)]. One case of Berardinelli-Seip syndrome or generalized Lipodistrophy is presented: generalized lack of adipose tissue, hepatosplenomegaly, increased development, hardness and prominence of muscles and phlebomegaly were present. In the presence of hormonal investigation (STH normal, LH and plasma testosterone increased) the possible pathogenesis of the syndrome is exposed. It is also striking the high incidence of this disorder in siblings.


Aging and senile cataracts: an integrated theory. Dedicated to professor Dr. F Hollwich on his 65th birthday. Earlier theories of cataract formation have been unsatisfactory and incomplete because they usually assigned a single causative factor to the lenticular changes of cataract. The older theories tended to restrict themselves to consideration of the lens itself, and so were necessarily limited in their premises. The recent rise of interdisciplinary study in medicine has demonstrated the need for a more fundamental and yet broader search for explanations to the disease process. Aging itself is a case in point, and it gives ophthalmologists the framework for an integrated and comprehensive theory of cataract formation, presented here. This new theory considers the alterations in the lens in terms of molecular-level actions that are known to be a part of the aging process-mutation, cross-linkage, and free radical reaction. The further study of these factors, already better understood in other disciplines such as biochemistry and genetics, may lead ophthalmologists to a more precise theory of cataract formation.


Some biochemical aspects of light effects on transparent eye tissues. The usefulness of biochemical studies on effects of light on transparent tissues of the mammalian eye is discussed in relation to the possible role of photobiological phenomena in aging and pathology of the eye. Particular emphasis is on effects of light on interaction between different cellular constituents of the corneal stroma which appear as a factor in regulation of the corneal metabolism. Daylight filtered through the walls of glass vessels was found to depress the incorporation of 14-C glucosamine into keratansulfate fraction of the bovine corneal stroma which appears not to be bound to collagen fibrils as it is extracted by 0.15M NaC1 at 4 degrees C without any morphological change in these fibrils. Since this depression was not found in the absence of the epithelium, secretions by the epithelium of specific substances affecting the keratoyctes are suggested. The possible relation of light effects on the hydration of the cornea is discussed.


The effect of dexamethasone on borderline ocular hypertension. The topical steroid testing with dexamethasone 0.1% (Decadron) of one eye of 36 specially selected borderline ocular hypertensive patients produced a positive response in 25%. Similar testing of the second eye of 4 monocular open angle glaucoma patients produced a positive response in 75%. The test was thought to provide guidance for closer observation of the positive reactors, indications for therapy, and a reduction in patient clinic visits.


Aniridia and congenital ptosis.

Aniridia and congenital ptosis. Congential ptosis associated with aniridia was found in 3 patients from 2 pedigrees. Nonsurgical aphakia, a condition not previously reported in association with aniridia, was also found in one case. The association of aniridia and congenital ptosis is suggested as evidence for the common mesodermal etiology of both anomalies.


Embolism of a cilioretinal artery following cardiac surgery. While embolic phenomena involving the central retinal artery or its branches have been often observed, reports of emboli to the cilioretinal artery are rare. A case is described in which a relatively young patient with atherosclerotic cardiovascular disease sustained an embolus to a cilioretinal artery following heart surgery.


Retinal vascular occlussion induced by oral contraceptives. A case of unilateral retinal vascular occlusion secondary to the use of oral contraceptives is presented. The vision was only slightly affected. Fundus examination revealed tortuosity of venules around the macular area and alteration of the pigment epithelium indicating low-grade retinal vein occlusion. Periodic ophthalmologic examination is suggested to women on oral contraceptives to prevent serious thromboembolic complications.


Hypertonic saline solution in corneal edema. Seventy-five patients (89 eyes) with corneal edema were treated with topical instillations of 5% hypertonic saline in a water soluble polymer solution (Adsorbonac). Ancillary therapy included glaucoma medications, IDU, corticosteroids, antibiotics and hydrophilic bandage lenses. The drops were instilled as frequently as required to maintain clarity, and visual acuity was utilized as the sole parameter of therapeutic efficacy. Primarily because of variations in etiology, concurrent therapy, and environmental factors, the results showed a high degree of individual variability. The therapy was uniformly well tolerated and a majority of patients demonstrated improvement in the visual acuity following use of the medication for a period of 3 months.


Statistics of eye collections.

Statistics of eye collections. Our data show cause of death is relatively unimportant as a factor in determining if donor eyes will be used for corneal transplantation. Two factors that are important are age of donor and time of donation (weekday vs weekend). Cultures taken at time of enucleation are positive 50% of the time. Treatment with antibiotics will reduce this to 20% to 30%. Most organisms are considered nonpathogenic and probably not important, but 15% of positive cultures of eyes used for corneal transplantation (about 4% of eyes obtained) had potentially pathogenic organisms present.


Multifocal serous choroidopathy.

Multifocal serous choroidopathy. Six percent of young and middle-age adults with idiopathic central serous choroidopathy were found to have bilateral multifocal areas of pigment epithelial detachments and transmissional defects during fluorescein angiography. The usual features of this chronic and recurring disease warrant its classification as a specific syndrome. The maculopathy is generally unresponsive to steroid therapy and may require photocoagulation to effect a cure.


Occlusion of cilioretinal vessels: case report. A 38-year-old man with poor vision in the left eye was found to have occlusions of 2 cilioretinal vessels in this eye producing a central scotoma. The incidence of cilioretinal vessels varies from 7% to 20%; yet, the paucity of reports regarding occlusions of cilioretinal vessels is self-evident. The occurrence of occlusion of 2 cilioretinal vessels, in the same eye, must be extremely rare.


Upper eyelid retraction after glaucoma filtering procedures. After glaucoma filtration surgery, 2 patients developed overaction of Müller's muscle with resultant upper eyelid retraction. We theorize that stimulation of Müller's muscle is caused by a sympathomimetic chemical in the aqueous that travels from the bleb, under the bulbar and palpebral conjunctiva, to Muüller's muscle. In one case excision of Muüller's muscle relieved the retraction. In the other case, preventing aqueous from reaching Müller's muscle reduced the retraction.


Effects of intravitreal prostaglandins on retinal vasculature. One dose of each prostaglandin preparation was injected into the vitreous body of the right eye of 64 rabbits. Doses less than 200mug caused no toxicity. Doses greater than 200mug exhibited the following changes observed by ophthalmoscopic observation, fluorescein angiography, histologic preparation, and electron microscopy: vascular leakage, vascular occlusion, hemorrhage, and retinal detachment. Electron micrographs revealed damaged retinal vascular endothelial cells. These changes were considered secondary toxic phenomena and did not occur at physiologic prostaglandin concentrations.


Prolonged pain after cyclocryotherapy performed with retrobulbar bupivicaine hydrochloride anesthesia. Ten patients received retrobulbar bupivicaine (Marcaine) in conjunction with cyclocryotherapy for medically unresponsive postpenetrating keratoplasty glaucoma and were found to experience significantly longer postoperative pain than 20 patients who recieved lidocaine (Xylocaine) anesthesia. The duration of pain was correlated with the need for narcotic analgesis whenever possible. We encourage further investigation into the etiology of the discomfort after cyclocryotherapy employing retrobulbar bupivicaine anesthesia.


[Formation of organic acids by an active strain of Act. rimosus and by an inactive mutant in relation to oxytetracycline biosynthesis]. Formation of organic acids by an active oxytetracycline-producing strain and an inactive mutant under conditions favourable (starch medium) and unfavourable (glucose medium) for the antibiotic biosynthesis was studied. It was shown that the active strain practically produced no organic acids on the starch medium. Under conditions unfavourable for the antibiotic biosynthesis the decrease in the activity level correlated with accumulation of marked amounts of pyruvic and lactic acids. The mutant possessing no capacity for the antibiotic biosynthesis produced significant amounts of pyruvic, acetic and lactic acids, the amounts of the acids markedly increased on the glucose medium. By the composition of keto acids the active strain and the inactive mutant did not differ.


[Study of the population makeup and antibiotic and transamidinase activity of Actinomyces streptomycini 773 stored for a long period in a lyophilized, dried state]. Studies on variation of the streptomycin-producing organism Act. streptomycini 773 on its storage in lyophilized state showed that prolonged maintenance (for 8 years) resulted in increased percentage of "oligospore" (up to 6.9 per cent) and asporogenic (up to 6.0 per cent) variants in the population. The variants had lower transamidinase and antibiotic activity.


[Action of antibiotic 1719 from a group of diazo compounds on hematopoiesis in laboratory animals and its pharmacokinetics]. Antibiotic 1719 administered intravenously to rats in a single dose of 6.0 mg/kg induced a transitory decrease in the number of myelocariocytes on the 2nd-5th day of its use mainly at the account of decreased numbers of lymphoid elements. Simultaneously momentory leucopenia (granulocytopenia) and more stable lymphopenia were observed. When the antibiotic was administered intravenously to dogs in a dose of 0.9 mg/kg 4 times and in a dose of 0.4 mg/kg 40 times, an insignificant decrease in the number of myelocarlocytes was noted. Leucopenia, lymphopenia and thrombocytopenia in the peripheral blood almost completely disappeared after discontinuation of the preparation administration. Leucocytosis (granulocytosis), lymphopenia and thrombocytopenia were registered in the dogs and rabbits treated with the antibiotic in doses of 1.5 and 3.0 mg/kg 3 and 11 times respectively. When the antibiotic was added to the rabbit blood serum in concentrations of 0.5-5 gamma/ml, 70 to 80 per cent of the preparation bound with the blood proteins. After a single intravenous administration of antibiotic 1719 to rabbits in doses of 10 and 15 mg/kg, it was detected in the blood only for 5 to 15 minutes after the administration in concentrations not exceeding 0.3 and 0.5 gamma/ml. The antibiotic penetrated into all organs in small amounts and persisted there for 1.5 to 3 hours after the administration. The antibiotic was excreted with the bile in amounts of 0.3-0.5 per cent of the dose administered for 1 to 2 hours after a single administration. The antibiotic was excreted with the urine for 3-4 hours after the administration in amounts of 3.5 per cent after a single administration and 60-72 per cent after multiple administrations.


[Use of a 2-part model of i pharmacokinetics of gentaniycin for maintaining a constant blood concentration in infusion intravenous (an experimental study)]. Maintenance of constant antibiotic blood levels within the required ranges may be accomplished with mathematical modelling of the antibiotic pharmacokinetics. The problem solvation was illustrated on gentamicin. The kinetic analysis of the curves of the drug excretion from the blood after a one-moment intravenous administration of the antibiotic to cats provided estimation of the constants for a two-compartment model of its pharmacokinetics. The constant values were used for calculation of the intravenous infusion rate for gentamicin and the load dose value providing attainance and maintenance of the drug blood levels within the required ranges. The experimental testing of the regiments of gentamicin infusion showed satisfactory correlation of the theoretically supposed and practically found antibiotic blood levels.


[Relationship of the reticulo-plasmocytic reaction of the bone marrow and serum hypergammaglobulinemia when tetracycline is administered to rabbits]. Administration of tetracycline to rabbits in doses of 10 and 40 mg/kg induced hyperplasia of the reticulo-plasmic tissue of the bone marrow correlating with increased levels of gammaglobulins in the blood serum. The pronounced reticulo-plasmocytal reaction of the bone marrow must be considered as manifestation of hyperplasia of the whole reticulo-histiocytal system of the host with impairement of differentiation of the reticular syncytium of the bone marrow.


[Sensitivity of certain strains of pathogenic Leptospira to streptomycin, the nature of resistant variants and the frequency of their occurrence]. Streptomycin sensitivity of 112 Leptospira strains isolated from domestic and wild animals was studied. Independent of the isolation period and nature the strains proved to be highly sensitive to the antiobiotic (MIC 0.1 to 0.5 gamma/ml). On the example of a clone strain of Leptospira it was shown with a fluctuation test that streptomycin resistance occurred spontaneously. Frequency of the streptomycin resistant mutations was determined for 5 clone strains of L. interrogans. It was 10-9 to 10-7 per a Leptospira.


[Lysozyme content in the blood serum and saliva of carriers of pethogenic staphylococci]. 90 serum and 273 saliva samples from pathogenic staphylococci carriers and healthy persons (control group) were studied. It was found that the state of pathogenic staphylococci carrying on the nose mucosa had no significant effect on the lysozyme levels in the blood serum, while assisted an increase in the content of the substance in the saliva. Increased lysozyme levels in the saliva of the pathogenic staphylococci carriers showed no clear connections with lysozyme production by the pathogens.


[Effectiveness of treating chronic cholecystitis by prodigiozain electrophoresis]. 136 patients suffering from chronic cholecystitis were treated in the phase of exacerbation with antibiotics in combination with prodigiosan. It was found that inclusion of prodigiosan into the therapeutic complex had a positive effect on the immediate and late results of the treatment. Since intramuscular administration of prodigiosan was accompanied by a number of side effects, a method of the drug administration by means of electrophoresis on the area of the bile bladder was tested. It was shown that prodigiosan administered by the method of electrophoresis totally preserved its stimulating capacity with respect to the host. As with intramuscular administration of prodigiosan, the general reaction of the host and positive dynamics of the clinical and laboratory indices of the active process were observed and the content of lysozyme in the blood phagocytes reliably increased. The method of prodigiosan administration by means of electrophoresis was better tolerated by the patients and no side effects characteristic of the drug intramuscular administration were noted. When indicated, the use of prodigiosan by means of electrophoresis is recommended.


Actinic granuloma. An annular connective tissue disorder affecting sun- and heat-damaged (elastotic) skin. Ring-shaped inflammatory lesions sometimes develop in the abnormal "elastotic" connective tissues of skin damaged by sun and heat. The lesions, which commence as papules and nodules, enlarge very slowly and may persist for years. Microscopical sections show that there is an infiltrate composed mainly of foreign-body giant cells, the cells being engaged in digesting and absorbing the abnormal elastotic fibers. The disorder, which occurs on several continents, should probably be regarded as a phenomenon of repair within damaged connective tissue. The name actinic granuloma indicates its external or environmental origin and distinguishes it from other granulomas with which it is constantly being confused. Actinic granuloma and granuloma annulare appear to be related. In granuloma annulare, a productive and resorptive process also occurs, but its nature remains obscure. Actinic granuloma may be misdiagnosed as "atypical necrobiosis lipoidica" or as a sarcoidosis. The subject of actinic damage to blood vessels deserves study.


Tar photoxicity and phototherapy for psoriasis. The photoxicity of coal tars was determined by comparing the ultraviolet light (UVL) energy required to produce erythema at tar treated sites (minimal phototoxic dose [MPD]) with the energy required to produce the same degree of erythema at untreated control sites (minimal erythema dose [MED]). The ratio of MED/MPD is the photoxic index (PI). Tars that were phototoxic had a PI of greater than 1. Using a UVA (320 to 400 nm) and a tuvb (290 to 320 nm) light source, 15 subjects and six tars were tested. All tars were phototoxic to UVA but not to UVB (P smaller than 0.0001). Although tar and UVL is a widely accepted treatment for psoriasis (Goeckerman therapy), the light sources employed at normal exposure times provide insufficient UVA energy to produce a phototoxic reaction to the tars are used. The therapeutic response seen in psoriatic patients treated with tar and UVL should therefore not be attributed to tar phototoxicity.


Effects of methotrexate esters on normal and psoriatic skin. The effect of several lipid-soluble folic acid antagonists on DNA synthesis in psoriatic and normal skin was studied. The skin samples were incubated in vitro with methotrexate, dichloromethotrexate, and their respective dimethyl esters, followed by exposure to deoxyuridine-3H to assay DNA synthesis radioautographically. Psoriatic epidermal cells were found to be selectively inhibited at lower concentrations (2 times 10-7 M) of these drugs than was normal skin. The ester derivatives were more active than the parent compounds, suggesting that increased lipid solubility of the compounds may potentiate their activity.


Psoriasis--changes in surface microtopography. Easily prepared adhesive slides have been used to obtain surface-layer biopsy specimens from psoriasis and other scaly dermatoses that occur on the limbs. Psoriasis obliterates the normal skin pattern, but the change is not specific. However, as psoriasis undergoes spontaneous or treatment-induced resolution, the skin surface pattern reappears and develops through a series of pattern changes that closely correlate with the clinical appearance of the lesion. This method may be used to monitor changes in the stratum corneum.


Mechlorethamine desensitization in therapy for mycosis fungoides. Topical desensitization to mechlorethamine (nitrogen mustard) contact hypersensitivity. Five patients with mycosis fungoides who had developed contact dermatitis to a nitrogen mustard, mechlorethamine hydrochloride, even in low concentrations (1 to 5 mg/100 ml), received daily total-body applications of extremely dilute solutions (0.01 to 0.1 mg/100 ml) of mechlorethamine. The concentrations of the drug were approximately doubled weekly if the patient could tolerate it, or they were raised more slowly if the patient could not. Attempts to desensitize one patient were discontinued since he was unable to tolerate a greater concentration than 1.0 mg/100 ml after trying for one year. Another patient was able to tolerate a concentration of 3 mg/100 ml after three months, at which time his skin had completely cleared and treatment was stopped. Three other patients were desensitized during a period of 8 to 13 months to the point of tolerating the full therapeutic concentration used in our clinic (20 mg/100 ml) without experiencing dermatitis or pruritus.


Acute, generalized panniculitis with amylase and lipase in skin. A patient had an unusual acute, generalized panniculitis. The patient had a five-fold elevation of urinary amylase level and a slightly elevated serum lipase leval without any signs or symptoms of pancreatic disease. A secretin test caused an eightfold elevation in urinary amylase level and some elevation of serum lipase and amylase levels, whereas study of duodenal drainage revealed no abnormalities. Skin specimens from the lesions showed considerable amylase and lipase activity, whereas specimens from controls and from subsequent patients with panniculitis showed no such abnormalities. Autopsy showed a normal pancreas, both grossly and microscopically.


Peutz-Jeghers syndrome with pigmented oral papillomas. The association of cutaneous and mucosal pigmentation with gastrointestinal polyposis has been well-described as the Peutz-Jeghers syndrome. A case is described of a patient who has evidence of gastrointestinal polyposis, diffuse and circumscribed macular hyperpigmentation, a nasal polyp, and the additional features of buccal mucosal pigmented papillomas.


Subcutaneous fat necrosis associated with pancreatic disease. Subcutaneous fat necrosis, a type of panniculitis, is a rare entity that is manifested by painless or painful subcutaneous nodules on the legs, buttocks, or trunk and is associated with pancreatitis or carcinoma of the pancreas, either of which may be asymptomatic. The histopathological findings are pathognomonic and consist of subcutaneous focal fat necrosis and "ghost-like" cells with thick, shadowy walls and no nuclei. Arthritis, particularly of the ankles, is a commonly associated finding. Distant foci of fat necrosis in pancreatic disease are probably due to the local action of hematogenous-borne trypsin and lipase. Since the underlying pancreatic disease may be asymptomatic, histopathologic study of all cases of panniculitis should be considered.


Life-threatening respiratory distress from mediastinal masses in infants. From 1972 through 1974, 5 infants with severe respiratory distress secondary to mediastinal tumors were treated in the Division of Pediatric Surgery of The Johns Hopkins thospital; The mediastinal masses included 2 intramural bronchial cysts, a giant esophageal duplication, a benign teratoma, and a highly malignant neuroblastomamindividualized management was carried out successfully in all: total resection of the bronchial cysts and teratoma; partial resection of the duplication cyst with stripping of the remaining mucosa from the contiguous esophageal wall, thereby preserving esophageal integrity; and excision of involved chest wall and tumor combined with radiotherapy and chemotherapy for the neuroblastoma. This experience emphasizes the potential for lethal respiratory distress from mediastinal tumors in infants and supports the experience reported by others of serious consequences if resection is not performed. Primary physicians and thoracic surgeons must be aware of the lethal potential of such mediastinal tumors among the many other "surgical" causes of respiratory distress in neonates and infants.


Electrocardiographic changes during surface-induced deep hypothermia. The influence of ether, halothane, carbon dioxide, and perfusion rewarming. The influence of halothane, ether, carbon dioxide, and perfusion rewarming on the electrocardiogram was studied in 37 dogs subjected to surface-induced deep hypothermia. Significant anesthetic-related differences in P-R, QRS, Q-T and R-R intervals during cooling were not apparent; however, reduced arterial pressure, ventricular fibrillation, and a greater tendency for bradycardia requiring supportive measures were noted at low temperatures with halothane anesthesia. The use of 95% O2/5% CO2 significantly reduced the QTc at low temperatures; Other phenomena, including the occurrence and significance of J waves, are discussed. The relationship of the electrocardiogram to clinical and pathological results was evaluated and indicates that (1) properly managed resuscitation (manual massage and defibrillation) is not a serious hazard, (2) ether in 100% oxygen is the agent of choice for surface-induced deep hypothermia with prolonged circulatory arrest, and (3) halothane may be used in a procedure combining surface cooling and perfusion rewarming if given in a mixture of oxygen and carbon dioxide.


Biochemical modifications of fascia lata for autologous valve replacement. The biochemistry of canine fascia lata was studied to assess the feasibility of tissue modification with a variety of cross-linking reagents and growth inhibitors in order to provide a more suitable material for heart valves. Chemical determinants for maximal reactivity were consequently established for several growth inhibitors, of which the hydrophobic ligands difluorodinitrobenzene, octadecylamine, and oleylamine were the most effective in preventing invasive cellular growth. This enhanced the longevity of atrial grafts in dogs as judged from morphological and histological examination of excised grafts.


Experimental pulmonary venous occlusion. Complete interruption of pulmonary venous return from the left lung in rabbits is compatible in some instances with prolonged survival with little systemic effect. The main cause of death less than 48 hours after interruption of pulmonary venous return is pulmonary-pulmonary aspiration and respiratory insufficiency due to spillover of frothy, bloody fluid, after which infection may play a part. Marked anemia after unilateral pulmonary venous ligation attests to the loss of blood into the lung. Death from unilateral pulmonary venous ligation did not occur if the corresponding main bronchus was ligated to prevent pulmonary-pulmonary aspiration; Despite ligation of the pulmonary veins the corresponding pulmonary artery remained patent.


Left ventricular aneurysmectomy in a child. Treatment of anomalous left coronary artery. Anomalous origin of the left coronary artery from the pulmonary artery with development of a massive left ventricular aneurysm in a 23-month-old child is described. Operative treatment included ligation of the anomalous origin, ventricular aneurysmectomy, and a saphenous vein bypass graft to the anterior descending coronary artery. The principles of ventricular aneurysm resection used in adults are applicable to small children with this complication of anomalous coronary artery origin.


Aberrant right subclavian artery aneurysm. Ten patients with aneurysm of an aberrant right subclavian artery have been previously reported. Dysphagia is not commonly part of the initial symptomatology, and the diagnosis is usually established by chest roentgenogram, esophagogram, and aortography. If operative intervention is planned, adequate preparation for bypass and thoracic aortic grafting should be made since the aneurysm may also involve the descending thoracic aorta at the site of origin of the aberrant subclavian artery. Since both ischemia of the involved arm and the subclavian steal syndrome may occur after division of the origin of the subclavian artery, resotration of arterial flow in the distal subclavian artery is preferred. An additional patient is reported in whom right subclavian-to-carotid artery anastomosis was used after the subclavian artery aneurysm was removed.


Free internal mammary artery graft. An improved surgical technique. An improved method of free internal mammary artery (IMA)-to-ascending aorta anastomosis for cornoary bypass is described. We interposed a small patch of vein with a suitable side-branch or brancyes in connecting the proximal end of a detached IMA or radial artery. Thirty-four free IMA-to-coronary artery bypasses were performed in 25 patients; 16 right IMA, 14 left IMA, and 4 radial arteries were used. Cornoary angiographic follow-up studies performed in all patients between two weeks and six months after operation proved that all grafts were patent and showing a larger lumen than is usually seen in undetached IMA grafts. Concomitantly marked relief of anginal pain was noted in all patients. Oour experience with this technique is very encouraging. All patients are being followed to evaluate long-term graft patency.


Follow-up of participants in a drug dependence therapeutic community. We interviewed by random sample 20 graduates and 20 dropouts from a drug dependence therapeutic community to identify any differences between groups. Although the two groups were from similar backgrounds at admission, the graduates seemed to do better after treatment. Throughout the follow-up period, the graduated spent proportionately less time addicted or in jail and proportionately more time employed or in school than those who dropped out of the treatment program. At follow-up, more graduates were available for voluntary abstinence and were abstaining from addicting drugs than were the dropouts. Also, at the follow-up interview, more graduates were employed or in school and fewer were legally involved than the dropouts. In the dropout group, abstinence in the follow-up period was correlated with longer length of treatment.


The oculo-cerebral-renal syndrome of Lowe. Clinical, light microscopical, ultrastructural, and biochemical studies were done on nerve and muscle biopsy specimens from five patients with the oculo-cerebral-renal syndrome of Lowe. Four patients were American Indians, a racial group in whom this disease has not previously been recognized. The hypotonia, areflexia, and diffuse atrophy of muscles are associated with slowed motor nerve conduction velocities, and the morphologic changes in sensory nerves are attributed to a "dying-back" phenomenon probably resulting from an unknown metabolic derangement.


Hereditary mental depression and Parkinsonism with taurine deficiency. An unusual neuropsychiatric disorder inherited in autosomal dominant fashion occurred in three successive generations of a family. Symptoms commenced late in the fifth decade in six affected patients and led to death in four to six years. The earliest and most prominent symptom was mental depression not responsive to antidepressant drugs or electroconvulsive therapy. This was accompanied by exhaustion, sleep disturbances, and marked weight loss. Later in the disease, symptoms of parkinsonism appeared, and respiratory failure occured terminally. The most recently affected family member was investigated biochemically late in his illness. Concentrations of taurine were greatly diminished in plasma and cerebrospinal fluid, and at autopsy, all regions of brain examined had a markedly reduced taurine content. Since taurine is a putative inhibitory synaptic transmitter, deficiency of brain taurine may possibly have caused the psychiatric and neurological manifestations of this disorder.


Brain peroxidase and catalase in Parkinson disease. Peroxidase and catalase activities were determined in various regions of parkinsonian brains and control brains from patients with nonneurological diseases. The highest peroxidase activity was localized in the substantia nigra of the normal brain. In Parkinson disease, the peroxidase activity was decreased in the substantia nigra, caudate and putamen. Catalase activity was also reduced in the substantia nigra and putamen of the parkinsonian brain. These enzyme changes may be causally related to the degeneration and depigmentation of the substantia nigra neurons in Parkinson disease.


Contralateral gaze deviation with supratentorial hemorrhage. Three patients with spontaneous supratentorial intracerebral hemorrhage had contralateral sustained conjugate gaze deviation. The autopsies disclosed large thalamic-basal ganglia hemorrhages whose caudal extension was limited to the midbrain. Current knowledge of oculomotor localization does not adequately explain this "wrong-side" gaze deviation, and the mechanism remains obscure. The present cases suggest that thalamic hemorrhage can produce contralateral gaze deviation without involving postdecussation horizontal oculomotor pathways. Contralateral gaze deviation is not a rare occurrence with deep supratentorial hemorrhages, and awareness of this confusing sign should assist in localizing intracerebral hematomas.


Ulnar neuropathy in bicycle riders.

Ulnar neuropathy in bicycle riders. Three patients, one of whom is described in detail, developed ulnar neuropathy following prolonged bicycle riding, with compression of the ulnar nerve at the level of the ulnar canal at the wrist.


Acute autonomic neuropathy. Its occurrence in infectious mononucleosis. A 13-year-old girl with acute onset of symptoms limited to autonomic dysfunction was found to be suffering from infectious mononucleosis. With symptomatic therapy, improvement gradually occurred over a period of seven months. The documentation of this case widens the spectrum of disorders to be considered as a cause of so-called acute pandysautonomia or autonomic neuropathy.


Clonidine in Parkinson disease.

Clonidine in Parkinson disease. Several theoretical considerations suggest that potentiation of central norepinephrine mechanisms may improve motor performance in patients with Parkinson disease receiving concurrent treatment with levodopa. Clonidine hydrochloride, an antihypertensive drug believed to directly stimulate brain norepinephrine receptors, was administered to a group of patients with relatively mild Parkinson disease and coexisting essential hypertension and to three patients with Parkinson disease manifesting the "on-off" response to levodopa. Although a significant antihypertensive effect was achieved, a change in parkinsonian disability could not be demonstrated.


Is the Negri body specific for rabies? A light and electron microscopical study. Since first described by Negri in 1903, the Negri body has been regarded as a pathognomonic finding in signifying the presence of rabies encephalitis. Negri bodies (light microscope) were found in the brain of a patient with conclusive evidence against the presence of rabies encephalitis. This case provided the opportunity for a pertinent review of the literature in bringing the subject into a reasoned perspective. A definitive etiologic diagnosis of rabies requires the use of electron microscopical or immunofluorescent methods or both.


Paramyxovirus-like structures in brains of multiple sclerosis patients. Twenty-four plaques obtained at autopsy from the brains of six patients with multiple sclerosis were examined under an electron microscope. Specimens for ultrastructural study were processed from the unfixed brain tissues at the time of autopsies. Intranuclear filaments with a diameter of 150 to 260 Angstroms of possibly two different types were seen in the macrophages and in unidentified mononuclear cells that were infiltrating the perivascular regions of four plaque areas from three patients. Intracytoplasmic reticular filaments with a diameter of 100 to 130 A were seen in the astrocytes and in unidentified cell processes in five plaques from three cases. A possible link between these intranuclear filaments and paramyxovirus is suggested.


Regional curare test in evaluation of ocular myasthenia. In 7 of 14 patients with clinically restricted ocular myasthenia gravis, the regional curare test showed latent peripheral involvement. The test consisted of the intravenous administration of 0.2 mg d-tubocurarine into an ischemic arm followed by repetitive supramaximal percutaneous electrical stimulation of the median or ulnar nerves. This produced a decrease in the amplitude of the initial evoked potential and a decrement of greater than 10% in the amplitude of the succeeding three to five potentials at rates of 3, 5, or 15 stimuli/sec. Three patients underwent transcervical thymectomy with subsequent improvement in both electrical and clinical findings. Evaluation of all patients with ocular myasthenia gravis should include regional curare testing of clinically uninvolved peripheral nerves. Thymectomy should be considered for patients with abnormal results.


Response of serum creatine phosphokinase to steroid hormone. Serum creatine phosphokinase activity increased significantly four or six hours after the administration of prednisolone in patients with muscular dystrophy of various types, whereas it did not increase in other muscular disorders. The extent of the response correlated inversely with the grade of disability. The prednisolone test may help to differentiate muscular dystrophy from polymyositis.


[Theory of traction. Determination of the optimal arrangement of metal in the dorsal traction of an olecranon fracture]. This is the analysis of external forces acting on the elbow joint and their influence on the appearance of bending forces, shearing forces and tensions along the ulna and their alterations with fractures of the olecranon. The influence of flexor muscles on the fracture site is being evaluated too. The fracture of the olecranon is being defined by means of statics. All disadvantages of a dorsal tension band i.e. uncertainty to neutralize all forces acting at the fracture site adequately, irregular interfragmentary compression, creation of unwanted stearing forces and moments, rest on its excentric localisation. The optimal distribution of hard ware is being evaluated.


[The lateral tension band. Demonstrated for fractures of the olecranon (author's transl)]. The lateral tension band generates continuous interfragmentary compression through two wires alongside the ulna. Without loss of compressive forces this procedure can be applied to proximal ulna shaft fractures which until now have been considered among fractures of the olecranon because the flexion forces at the fracture site are neutralized. Fractures of the patella are the second main indication for this procedure. All disadvantages of the "classical" dorsal tension band are being avoided by centric compression.


[Measurement of bipolar interfragmentary compression on model bone by variation of the tension band of a fracture of the olecranon (author's transl)]. Previous experiments with dorsal or lateral tension band have been tested and confirmed on model bone. The lateral tension band is superior to the dorsal because it can neutralize all forces across the fracture site without creation of unwanted adverse forces.


[Better stabilisation of the femoral neck fractures with drawing-screw-osteosynthesis according to AO principle (author's transl)]. Author drafting the biomechanical problems, which hinders the possissibility of a good fixation of the fractured femoral neck in the old age, reviews a compression-osteosynthesis according to AO drawing-screw principle.


[Can we reduce complications of treatment of femoral neck fractures with better stabilisation of the osteosynthesis? Results of a compression-osteosynthesis (author's transl)]. The results of a compression-osteosynthesis of the fracture of the femoral neck on the evidence of 172 cases realizing the principle of a drawing-screw-compression of the AO have been reported. The results will be compared with the data of collected statistics of other types of nailing of the femoral neck and it will be established, that the better stabilisation of fractur will be manifest in the results too and will be realised in the decrease of complications (slipping of the nail, redislocation, pseudarthrosis, avascular necrosis of the head).


[Pulmonary function tests and spiroergometric parameters during rehabilitation of patients with idiopathic scoliosis (fusion of the spine with Harrington rod and training) (author's transl)]. 11 female patients with idiopathic scoliosis underwent spinal fusion surgery after Harrington. Additionally the patients were exercised before and after surgery by a special program. During the period of rehabilitation the usual spirographic measurements were carried out and some spiroergometric parameters were measured at standardized ergometric work loads. The diminished vital capacity and the practically normal forced vital capacity were not changed significantly, but the maximum voluntary ventilation was enhanced distinctly. The resting heart rate, primarily far above normal level, decreased significantly at the end of the exercise period and approached normal range. Maximum heart rate corresponded always to the mean values of normal subjects. Instead of a nearly constant increased minute volume of respiration, respiratory frequency and specific ventilation (respiratory equivalent) the maximum 0-2 uptake and maximum 0-2 puls increased significantly. These changes can be explained by an improvement of the uneven distribution of perfusion and ventilation, due to the combined surgical and exercise treatment.


[Peculiarities in the sterile operating cabin (author's transl)]. With helium filled bubbles from a bubble generator we could demonstrate dangerous turbulences around the operating area in the sterile operating cabin (Greenhouse). The bubbles follow a pattern corresponding to the direction of the turbulent air-stream. Special reference is made to the effect of objects and the surgeon within the area of down flow laminar airflow.


Rhincerebral phycomycosis and internal carotid artery thrombosis. This is a report of a case of internal carotid artery occlusion associated with rhinocerebral phycomycosis. In 18 autopsied similar cases that have been reported previously, hyphae were described in the walls of the internal carotid artery. Four survivors have been reported even though arteriograms demonstrated internal carotid artery occlusion, and a high index of suspicion for this complication should be maintained in all patients with rhinocerebral phycomycosis.


The modified Tokyo larynx: an improved pneumatic speech aid. The Tokyo, or Japanese, artificial larynx is a pneumatic speech aid with superior sound production used in the rehabilitation of laryngectomized patients. Although there are some difficulties with its use, modifications have been developed that eliminate the major problems. Three brief case reports demonstrate the effectiveness of this speech aid when properly prescribed.


Otoadmittance measurements in cases of dual ossicular disorders. Audiologic evaluations, including otoadmittance measurements, were obtained on two patients, each of whom had dual, series-connected disorders of ossicular fixation and disarticulation. In one case, the disarticulation was the lateral-most disorder; in the other case the fixation was the lateral-most disorder. In both cases, it was the lateral-most disorder that had the dominant effect on the otoadmittance of the tympanic membrane, due to the fact that the sites of the two disorders were connected in series with the tympanic membrane.


Nonlamellar new bone formation in the anterior attic recess. An area of nonlamellar new bone formation was observed in the anterior epitympanic region of 27 randomly chosen human temporal bones. The donors ranged in age from 9 to 80 years and had no evidence of ear disease or systemic skeletal or metabolic abnormalities. The frequency of this finding suggests that it is a normal feather of the human anterior attic recess.


Styloid process neuralgia: myth or fact. Five cases of enlogated styloid processes sent in a 12-month period prompted a review of this subject and a reevaluation of the condition as it relates to other neuralgias of the head and neck. We review the head and neck pain syndromes and offer diagnostic criteria that will aid in the differential diagnosis and will facilitate appropriate management.


The outset of chronic secretory otitis media: a histopathological study of the earliest stage. Histopathological study of the earliest stage of secretory otitis was made in a 3-month-old infant. The entire mucosa was examined by the whole-mount method, with determination of gland count and goblet-cell density, followed by assessment of serial sections. The first changes are inflammatory with lymphocytic infiltration, dilatation, and increase of blood vessels. These again induce metaplasia into pseudostratified, ciliated epithelium, increased in goblet-cell density, and formation of intraepithelial and subepithelial mucous glands. Basal cells divide and grow down into lamina propria, giving rise to a solid cylinder that gets canalized. Cells of this cylinder differentiate into ciliated and mucous cells, so that tubules acquire a lining of typical pseudostratified, ciliated, columnar epithelium. The most important processes in the early stage of secretory otitis are hyperplasia, differentiation of epithelial cells, and gland formation. When glands have completed their development, they produce mucus that accumulates in the middle ear, and the disease enters the secretory stage.


Aural abnormalities in partial DiGeorge syndrome. DiGeorge syndrome patients frequently have multiple anomalies of the craniofacial, cardiovascular, and visceral structures in addition to thymic and parathyroid hypoplasia. Gross and microscopic aural abnormalities occurring in a patient with partial DiGeorge syndrome are presented and compared with findings from the only other known temporal bone report.


Malignant fibrous xanthoma (xanthofibrosarcoma) of the larynx. The xanthofibrosarcoma is a malignant variant of fibrous xanthoma. It is a rare tumor that derives from histiocytes. A case believed to be the first xanthofibrosarcoma reported in the larynx is presented. Differentiation between this tumor and benign lesion was difficult. The tumor proved malignant by metastasizing. Although few fibrous xanthomas become malignant they should raise a high index of suspicion when they are large, have infiltrative margins, and tend to recur locally. Treatment is by wide surgical excision. Close follow-up is mandatory. The prognosis once metastases appear is extremely poor.


Occult schwannomas of the vestibular nerve. Five small occult schwannomas of the vestibular nerve were discovered on routine examination of 893 serially sectioned temporal bones of 517 individuals. Three arose from the superior division, one from the inferior division, and the other had a multicentric origin from both divisions of the nerve. Location and size of these tumors indicate that clinical diagnosis would have been difficult or impossible by any method of study. The finding of vestibular schwannomas in 0.9% of individuals in this series, indicates the high incidence of this tumor in the general population. The much lower incidence of diagnosed symptomatic tumors in the general population can only be explained by the conclusion that this neoplasm exhibits considerable variation in growth characteristics. Usually the tumor enlarges so slowly as to be of no health importance, but occasionally it grows more rapidly to become symptomatic and require surgical removal.


Allergic management of Meniere disease.

Allergic management of Meniere disease. Twenty-eight patients with Meniere disease were selected on the basis of a positive allergic history. Factors other than allergy that might produce the signs and symptoms of endolymphatic hydrops were first diagnosed and controlled with appropriate management. Allergic diagnosis and management consisted of testing and treating inhalant allergies according to the methods of Rinkel. Foods were first tested using the Bryant's modification of Black's cytotoxic food test. All positive foods were eliminated except for those considered extremely difficult to avoid. These were managed using the provocative skin food test and neutralization method of Lee et al. All patients in this study were under allergic management for a period of 14 to 29 months. During this time, labyrinthine symptoms were improved in nine cases and in 19, there was no change.


Swimming: stress and training.

Swimming: stress and training. The short term and the training effects of water immersion and swimming on ventilatory and circulatory parameters of the human organism were described using our own results and data from the literature. It is suggested that swimming has not only the common positive effects on the physical efficiency observed in other types of sport but seems to improve the orthostatic regulation of the circulation. Furthermore, the physical effects of water immersion and the special pattern of muscular activity during swimming favour the adaptation of the heart to the circulatory demands. This advantage of swimming might explain its known beneficial effect in preventive and curative medical treatment.


Arterial baroreceptor function in differential cardiovascular adjustments induced by central thermal stimulation. Dogs were anesthetized with sodium pentobarbital, relaxed with succinyl choline and were kept under artificial ventilation. Both carotid bifurcations were denervated and the Vagus nerves were cut in the neck. Regional blood flow in the skin and the intestine, cardiac output, heart rate and arterial pressure were determined before, during and after spinal cord heating and cooling. Further experiments were performed in which, in addition, sympathetic effects on the heart were excluded by exstirpation of the caudal cervical and stellate ganglia or by beta-receptor blockade. The cardiovascular responses were compared with those obtained in a preceding investigation from dogs with intact baroreceptors and vagus nerves. As in intact dogs, appropiate thermoregulatory adjustments of skin blood flow were induced by thermal stimulation of the spinal cord after baroreceptor denervation and vagotomy. However, blood pressure homeostasis was lost. The pattern of cardiovascular ajustments during heating consisted in cutaneous vasodilatation intestinal vasoconstriction and, due to sympathetic activation an increase of heart rate and cardiac output. This pattern was qualitatively identical with that intact animals. During spinal cord cooling the cardiovascular response pattern consisted in cutaneous vasoconstriction, intestinal vasoconstriction and, depending on cooling intensity, a reduced or unchanged sympathetic influence on the heart. This pattern differed considerably from what in intact animals but basic features were still present as indicated by opposite changes of cardiac and vascular sympathetic tone during cooling. It is concluded that the baroreceptor signals play no primary role in the generation of differential vasomotor responses under the present experimental conditions. This confirms assumptions made on the basis of observations in animals with intact baroreceptor input. However, baroreceptor signals contribute significantly to blood pressure homeostasis which is normally maintained during spinal thermal stimulation.


[Histogenesis of the immune system of the "nude" mouse. II. Postnatal development of the thymus: a light microscopical study (author's transl)]. The thymus of the homozygous nude mouse embryo is laid down normally. From the 13th day post conceptionem (pc) onwards, however, a maldevelopment takes place (Groscurth und Kistler, 1974). As a result, the anterior mediastinum of the newborn nu/nu mouse contains a rudimentary epithelial organ which resembles parts of an embryonic exocrine gland. In this paper, the light microscopical findings of the postnatal development of the thymus in homo- and heterozygous nude mice are reported. Homo- and heterozygous nude (nu/nu and nu/+) mice with the genetic background BALB/c were kept under specific pathogen-free (spf) conditions. Three nu/nu and three nu/+ female mice were sacrificed at the following developmental stages: newborn animal, 1st, 2nd, 3rd, 6th, 9th as well as 12th week postpartum (pp). The organs were fixed in Bouin's solution and embedded in paraffin wax. Serial sections (5 mu) were stained with hematoxylin and eosin. The bilobed thymus rudiment of the newborn nu/nu mouse consists of branching ducts. From the 2nd week post partum (pp) onwards, their epithelial cells proliferate. At the same time, some of these cells begin to differentiate into serous and mucous cells. In some parts of the rudiment, they also form thyroid-like follicles. The exocrine cells secrete their products into the lumina of the ducts. As there is no connection between the thymus rudiment and either the epidermis or the digestive tract, an accumulation of secretory products takes place, resulting in a dilatation of the whole duct system. Therefore, the thymus rudiment of the 12-week-old nu/nu mouse consists of a number of communicating cysts which are lined by a flattened epithelium. Cysts lined by an epithelium can also be observed within the thymus of the nu/+ mouse. Two types must be distinguished..


The relationship between the latent period and animal age in the development of foreign body sarcomas. Either porous polyester-polyurethane cylindrical sponges with a diameter of 12 mm (thickness 6 mm) or rectangular sponges (dimensions 120 times 20 times 5 mm) were implanted paravertebrally in the subcutis of a total of 118 rats of different ages (1-15 1/2 months). It was established that the rate of tumor formation increased with the size of the implant from 12.1% (cylindrical sponges) to 26.6% (rectangular sponges). Furthermore is could be shown that in animal experiments it is the age of the rats that plays the decisive role in sarcogenesis and not the latend period (time from the implantation until development of the tumor), in that young animals first develop malignant mesenchymal tumors after a mean 17.2 months whereas in old rats these had already developed after 6.3 months.


[New functions and variables to characterize and compare vectorcardiograms (author's transl)]. 1. The variability of electrographic data used up to now is too large to discriminate easily between normal and abnormal. 2. This variability is partly caused by errors in the measuring process and its consequences. A sepcial difficulty is found in determining the beginning and the end of QRS, so that instantaneous vector magnitudes related to the starting or ending moment of QRS will have a high variance and therefore a low comparability. Displacements of the heart will play an important role as a source of errors. 3. It therefore seems to be more appropriate to describe structure and changes in time of the vector loop. To this end 3 new functions v, w and u are described, all three invariant towards positional changes of the heart in space. The term v means a time-dependent function describing the first derivative of the length of the instantaneous resulting vector of all electrical sources. The term w indicates the projection of the first derivative of the instantaneous vector into a plane orthogonal to the resulting vector. Therefore, v is dependent on the change of all resulting electrical forces, whereas w is the velocity of the peak of the resulting vector on its way along the vector loop. The interpretation of u is complicated; u is a measure of how much the vector leaves a plane, in which it normally more or less remains; u is therefore a measure for the edgeside view of the vector loop. 4 These data are combined with the well-known vectorial data to form a system of vectorial description. 5 The interpretability of these data in physiological terms is exemplified. The description presented here allows to go back to cardiac processes in the proper sense and to largely elimenate external influences like those of the thoracic shape on the ecg and vcg. 6. This way of describing an ecg is specially adapted to the discrimination of normal and abnormal in preventive tests.


Electron microscopic autoradiographic localization of carbocromene in the coronary vessel walls and myocardium. The ultrastructural distribution of 14-C- and the 3-H-carbocromene in monkeys and rats showed a characteristic pattern in the coronary artery wall and the heart muscle. The radioactivity was found to be located on the coronary vessel wall mainly in the tunica media over the smooth muscle cells and in the myocardium over the contractile elements and the mitochondria.


Fine structure and pinocytic activity of the visceral epithelium of the rat yolk sac incubated in a culture medium with or without goat antirat-placenta-IgG. The fine structure and pinocytic activity of the rat visceral yolk sac epithelium were examined electron microscopically after incubation in Krebs-Ringer-Phosphate solution containing either 125-I-labeled albumin or goat antirat-placenta-IgG or both compounds simultaneously. Addition of 125-I-albumin to the incubation medium stimulates the pinocytosis, whereas the addition of goat antirat-placenta-IgG, cross-reacting with the yolk sac tissue, causes a diminution of the pinocytic activity of the yolk sac epithelium. Fine structural alterations and lesions are generally noticed. Preincubation of yolk sacs in Krebs-Ringer-Phosphate solution containing goat antirat-placent-IgG and the subsequent postincubation in a new Krebs-Ringer-Phosphate medium with 125-I-albumin does not restore the original pinocytic activity of the visceral epithelial cells.


[The variability of the QRS loop in the orthogonal lead system of frank and schmitt (SVEC III) (author's transl)]. A method has been previously described, to test the accuracy of lead fields. This method is used here to compare in 7 persons the relative validity of the two orthogonal lead systems of Frank and Schmitt (SVECC III). The variables the variation of which characterizes the validity of the systems, are the spatial position (represented by the spatial angles of the normal of the broadside view) and the variations in shape of the vector loops. The latter are measured by a comparison of the length of vectors in a distance of 5 degrees, starting with the maximal vector and proceeding from here to both sides. The vectors of loops in two different heart positions are compared by means of their correlation coefficients, and one of the loops is rotated in space as long as this correlation coefficient reaches a maximum. The data are handled by a computer. The optimal correlation coefficients, the regression coefficients and the differences in the spatial angles of the planes, in which the loops show their broadside view, are compared. The Frank system has a significantly lower variability of these values, by extreme dislocations of the heart, either by respiratory or by positional dislocations.


Quantitative evaluation of retrograde arterial flow in chronic experimental arteriovenous fistulas. A 2 cm long iliac av. fistula is established in 13 dogs. Flow measurements are performed in the fistula limbs and the adjacent arteries immediately (stage I), as well as 3 months (stage II) and 6 to 12 months (stage III) post-shunt. The following results are obtained: 1) In the acute stage, average flow in the distal fistula artery is very small but directed towards the periphery. In stages II and III a progressively increasing retrograde flow directed towards the fistula is regularly measured in the distal fistula artery. 2) Even in the acute stage a considerable retrograde flow is measured in the distal fistula artery when the proximal artery is clamped. Likewise, in stages II and III, this "free" retrograde flow (after occlusion of proximal fistula artery) is 40 to 60% higher than the spontaneous retrograde flow. 3) In chronic av. fistulas, the "free" retrograde flow in the distal fistula artery decreases significantly after occlusion of the adjacent tail artery and the contralateral iliac artery. It can thus be calculated that in chronic iliac av. fistulas the tail artery contributes approximately 44% and the contralateral iliac artery 22% to retrograde arterial fistula flow. The remaining 34% of retrograde flow are mainly derived from collaterals connecting side-branches of the abdominal aorta with the distal arterial limb. 4) These extensive collaterals adjacent to a chronic iliac av. fistula are demonstrated angiographically and by post-mortem vascular casts. 5) In all stages, occlusion of the proximal fistula artery simultaneously increases flow in the tail artery and contralateral iliac artery by more than 50%. This stresses the major contribution of these arteries to retrograde arterial fistula flow. 6) Successive occlusion of the tail artery and the contralateral iliac artery in stages II and III results in a nearly identical per cent decrease in "free" retrograde flow and in pressure (measured in the distal fistula artery). Even in the pre-fistula control stage, this occlusion experiment induces the same relative pressure-drop in the distal iliac artery. The proportional contribution of the collateral pathways to retrograde arterial fistula-flow and -pressure remains unchanged in the chronic stages post-fistula in spite of the tremendous expansion of collateral vessels within one year. These findings indicate that the three main collateral networks adjacent to the iliac artery all expand proportionally to their pre-fistula status in the months following construction of a large iliac av. fistula. This strongly suggests that the extensive interarterial anastomoses in a chronic av. fistula are all preformed collaterals which have gradually expanded.


[A longitudinal study of the relationship between the pulse wave velocity in the aorta-iliaca vessel and the blood pressure (author's transl)]. Temporary hypertensive increases in blood pressure, or variations in blood pressure when there was an already existing hypertension, in which the blood pressure either moved within the limits of hypertensive blood pressure values or temporarily returned to normal, occurred in 129 men ages 23-85, in whom repeated measurements of the blood pressure and pulse wave rate (PWG) were carried out in the aorta and iliac artery in the course of a longitudinal study over years. Both categories--temporary and chronic hypertensives--showed significant differences in the height of the PWG increase per 10 mm Hg (delta-c-p). The delta-c-p value for the chronic hypertensives (n equals 43) was 0.73 plus or minus 0.35 m/sec, that of the temporary hypertensives 0.56 plus or minus 0.24 m/sec (p smaller than or equal to 0.01). The mean value for both groups was 0.62 plus or minus 0.29 m/sec. Delta-c-p increased with age (0.54 m/sec yields 45th year; 0.60 m/sec from 46-55 years; 0.61 m/sec from 55-65 years; 0.67 m/sec at 66 and over). The increase of delta-c-p with age is caused by the increase in chronic hypertension. Delta-c-p was constant over a mean pressure range of 90-190 mm Hg in temporary and chronic hypertensives, irrespective of the amount of the (individual) mean difference in pressure, but it was distinctly greater in chronic than in temporary hypertensives. On lowering pressure, the delta-c-p was also greater in chronic than in temporary hypertensives. When normal pressures were attained, temporary hypertensives showed no differences from the PWG of normotensive of the same age. The differences between temporary and chronic hypertensives are explained by the different relations in the structure of the wall of the aorta, but especially because the function of the muscular layer was better maintained in temporary hypertensives. The raising of the PWG in temporary hypertensives is probably caused by the increased tension in the wall alone. Whether, in addition to the increased incorporation of collagen and a rarification of the smooth muscle, the thickness to radius ratio also increases above that usual for the age group in chronic hypertension is still not clear, but it is not essential for the explanation of the greater increase in the delta-c-p. The longitudinal delta-c-p values obtained in individual subjects confirms the transverse delta-c-p findings, with regard to size and age group, which were obtained by comparisation of cross sections of groups of normotive and hypertensive subjects.


[Theory of methods to compare lead fields in electrocardiography (author's transl)]. A method is theoretically described to test the accuracy of various lead system of the ecg. The priniciple of this method consists in the following procedure. The heart position is changed maximally in a proband by varying the position of the body and by deep inspiration and exspiration. If the lead field is parallel, the recorded vector loops should by conventible into each other by merely rotating them electronically, because the cardiac determinants of the veg will scarcely be changed by a change in heart position. The deformations of the veg in the edgeside and broadside view are an appropriate measure of the inhomogenities (the "accuracy") of the lead field, mostly caused by the configuration of the chest and the inhomogeneous conductivity of the tissues and the resulting lack of parallelity in the lead lines of the field. Criteria to test the form of the vector loop are developed, measuring quantitatively the similarly of the loops recorded in different heart positions. The "best" lead is regarded to be that with greatest similarity of the loops in extreme dislocations of the heart.


Vocalisation via a cuffed tracheostomy tube. A new prinicple. A thin catheter mounted on the upper surface of a tracheostomy tube enables a flow of air to reach the vocal cords and makes vocalisation possible during artificial ventilation.


Surgical treatment of ventricular tachycardia after epicardial mapping studies. Two patients with intractable life-threatening ventricular tachycardias have been studied using intracardiac electrograms and programmed electrical stimulation of the heart. Both patients have shown to have an underlying re-entry mechanism in the ventricles as the basis for the tachycardias. Both patients underwent epicardial mapping studies at cardiac surgery, and the site of re-entry was established. In one patient the re-entry front was found to start in the posterobasal region of the left ventricle and in the other patient the re-entry front was found in the anterobasal region of the right ventricle. In both patients surgical interruption of the re-entry front was carried out. Both patients are alive and free from tachycardias at the time of writing.


Problems concerning assessment of anatomical site of accessory pathway in Wolff-Parkinson-White syndrome. Twp patients with type B WPW syndrome and reciprocal tachycardias have been studied using intracardiac electrograms and programmed electrical stimulation of the heart. One patient, who had a right-sided accessory pathway giving the surface electrocardiographic appearances of type B WPW syndrome, was shown to have an additional left-sided accessory pathway as occurs in type A WPW syndrome. This concealed left-sided atrioventricular connexion formed the retrograde pathway during reciprocal tachycardia. In the second patient the appearances of type B WPW syndrome were shown to be caused by an accessory pathway between the atrial septum and the right side of the interventricular septum rather than an accessory pathway in the right atrioventricular groove. The significance of these findings when considering surgical interruption of an accessory atrioventricular conduction pathway is discussed.


Factors influenceing long-term prognosis in male patients surviving a first coronary attack. Three hundred and sixty-four men who survived a first episode of acute coronary insufficiency or myocardial infarction for 28 days were admitted to a coronary heart disease secondary programme between 1 January 1961 and 31 December 1971. Of these, 252 have been followed for at least 4 years. The 4-year mortality was 13.5 per cent (34 patients). The average mortality was 3.4 per cent but an excess of deaths occurred during the first year of follow-up. Of 11 characteristics measured during the acute attack, only severity of the attack was significantly associated with poor 4-year survival. Cigarette consumption after infarction was significantly less among those surviving the 4-year period when compared with decedents. Follow-up systolic and diastolic blood pressure levels were significantly lower among decedents. No significant differences were noted in serum cholesterol levels and in mean weight, The presence of post-infarction angina did not affect the prognosis.


Idiopathic giant cell myocarditis--a distinctive clinico-pathological entity. Eleven cases of idiopathic giant cell myocarditis are described, The pathological features are unmistakable with serpiginous areas of myocardial necrosis, at the margins of which giant cells can be seen on histological examination. The aetiology of the condition remains obscure but associated pathology suggests that altered immunity may be a factor. The rapid clinical course is, however, highly suggestive of an infective cause though none has been found.


Ejection phase indices of left ventricular performance in infants, children, and adults. A validatory study of quantitative single plane left ventricular cineangiography is presented, using human left ventricular casts ranging in size from 1.6 to 135 ml. Good correlation was found between actual and calculated volumes (r=0.967). 62 patient studies were carried out and the value of the usually calculated indices of left ventricular performance were compared to one another. Ejection fraction and mean rate of circumferential fibre shortening (mean Vcf) were found to be the best discriminators of abnormal left ventricular function, and, on the basis of the presented data, it is suggested that mean Vcf is the more sensitive index of left ventricular performance.


Complete interruption of aortic arch, without persistent ductus arteriosus, in an adult. A case of complete interruption of the aortic arch in an adult is presented and the previous 8 reported cases are reviewed. Obliteration of the ductus is a feature of these cases, in contrast to the more common variety found in early childhood. Comments are made on the clinical distinction between the adult type of complete interruption of the aortic arch and coarctation of the aorta.


The role of protein and lipids in stabilizing the activity of bovine heart succinate dehydrogenase. When incubated in an air atmosphere, solubilized succinate dehydrogenase (succinate:(acceptor) oxidoreductase, EC 1.3.99.1) quickly loses the capability to recombine with membrane components to catalyze mitochondrial related electron transport activities. At 0 degrees the loss in reconstitution capability is a first-order process; the half-life of the enzyme is 1.6 hr at this temperature. The enzyme is stabilized by recombining it with submitochondrial particles or with a cytochrome b preparation-phospholipid mixture. The presence of the cytochrome b preparation in the succinate dehydrogenase-cytochrome b-phospholipid complex is obligatory, indicating that protein-protein interactions between succinate dehydrogenase and other membrane components are important in stabilizing the capability of the flavoprotein to transfer electrons to other respiratory components. Treatment of this complex with phospholipase C results in loss of most of the succinate-dichlorophenolindophenol reductase activity and almost complete hydrolysis of phospholipid. Succinate dehydrogenase maintains its capability to participate in mitochondrial electron transport for several hours if the phospholipase treated complex is reconstituted with lysolecithin at the time of assay. Phospholipids are therefore not required for the stabilization process, but rather for formation of an active reductase complex. A lipophilic environment, if required for stabilization, can be provided by diglycerides. Diglycerides also can provide an environment conducive to electron transfer from succinate to ubiquinone but do so less efficiently than intact phospholipids.


Kinetic and equilibrium studies of the ligand binding reactions of eight electrophoretic components of sperm whale ferrimyoglobin. The reactions of eight electrophoretic components of sperm whale ferrimyoglobin with fluoride, azide, and cyanide have been studied. There do not appear to be significant differences in rate constants or equilibrium constants among the various components. We conclude that at pH 7.0 in 0.05 M potassium phosphate these ligand binding kinetics and equilibria are insensitive to the net charge on the protein. The variation of the azide equilibrium constant with ionic strength from mu 0.01 M to 0.11 M is not in accord with the predictions of the Debye-Hückel theory. On the other hand, azide association kinetic and equilibrium constants are respectively six- and threefold greater for beef ferrimyoglobin than for the isoelectric whale ferrimyoglobin (band V). An examination of the data for whale, horse, and beef myoglobins reveals that large differences in azide (but not CO) association rate constants are associated with amino acid substitutions at residues 45 and 99 in the heme cavity.


The amino acid sequence of ragweed pollen allergen Ra5. The complete amino acid sequence of Ra5, a ragweed pollen allergen, has been determined. Allergen Ra5 is a low molecular weight protein of 45 residues derived from Ambrosia elatior, the short ragweed. It contains no detectable carbohydrate or lipid and has four disulfide bridges. The total structure was determined on 1.4 mumol of material and indicates that structural analysis is increasingly possible on relatively small amounts of highly purified material when a combination of automated and manual sequencing techniques and highly sensitive detection systems is employed. This represents the first complete amino acid sequence of a ragweed allergen and it should provide a basis for many structure-function correlative experiments in the field of immediate hypersensitivity.


Association of tissue-specific histones with deoxyribonucleic acid. Thermal denaturation of native, partially dehistonized, and reconstituted chromatins. First derivative thermal denaturation profiles were compared for chromatin samples prepared from chicken erythrocytes, chicken liver, and sea urchin (Strongylocentrotus purpuratus) sperm. Selective dissociation of various histone fractions, including tissue-specific F2c and gamma histones, was manifested in characteristic changes of the thermal denaturation profiles. It was concluded that the binding of individual histone fractions to the DNA can be identified with paricular temperatures of thermal denaturation. This observation was tested by denaturation experiments on hybrid chromatins. Chicken erythrocyte chromatin devoid of F2c histone and reconstituted with isolated liver F1 histone denatured like chicken liver chromatin. Conversely, chicken liver chromatin devoid of F1 histones and reconstituted with isolated F2c fraction exhibited a thermal denaturation profile characteristic of the chicken erythrocyte chromatin. In other words, the thermal denaturation profile of reconstituted chromatin was determined approximately by the sum of contribution histone fractions. The obvious distinctions recognized among the derivative thermal denaturation profiles of compositionally different nucleoproteins suggest that thermal denaturation sensitively detects variations in histone content and therefore is a valuable tool for the routine characterization of chromatin preparations.


Interaction between spin-labeled acyl-coenzyme A and the mitochondrial adenosine diphosphate carrier. Spin-labeled long-chain (m,n)acyl-CoA's (general formula: CH3(CH2)mCR(CH2)nCOSCoA, where R is an oxazolidine ring containing a nitroxide) inhibit anion transports through the inner mitochondrial membrane at low concentrations as ordinary long-chain acyl-CoA's do. The inhibition constant relative to the inhibition of the ADP transport in heart mitochondria by spin-labeled palmityl-CoA and stearyl-CoA is of the order of 10-7 M, a value which is similar to that found for natural long-chain acyl-CoA's. A short-chain spin-labeled acyl-CoA (C5) showed no inhibitory effect in the range of concentrations tested (up to 30 muM). (2) (10,3)Acyl-CoA added to heart mitochondria at low concentrations exhibits spectra corresponding to an immobilized probe. The corresponding free fatty acid shows a higher freedom of motion between 0 and 30 degrees. The same differences in spectra of spin-labeled acyl-CoA and spin-labeled free fatty acid were found in inner membrane vesicles from rat liver mitochondria, but not in outer membrane preparations. (3) The selective interaction of spin-labeled acyl-CoA with the ADP carrier is indicated by the release of this interaction by specific ligands of the ADP carrier, such as ADP or ATP, carboxyatractyloside, adn bongkrekic acid. ADP (or ATP) and carboxyatractyloside rendered the spin-labeled (10,3)acyl-CoA nearly as mobile as the (10,3) free fatty acid. No effect was obtained with AMP, GDP, or UDP which are not transported by the ADP carrier. Bongkrekic acid, another specific inhibitor of the ADP carrier, was inactive when added alone; however, it was effective when added together with amounts of ADP which are ineffective per se. (4) The electron spin resonance (esr) spectrum observed at low concentrations of (10,3)acyl-CoA arises from (10,3)acyl-CoA bound to the  ADP carrier. At higher concentrations the (10,3)-acy-CoA is more suggesting that the bulk of the label is also present in the lipid phase of the membrane. Spin-labeled acylCoA's incorporated into a sonicated dispersion of lipids extracted from heart mitochondria exhibited similar mobile spectra. (5) When the oxazolidine ring is moved down the hydrocarbon chain of the acyl-CoA, the binding features tended to disappear. Whereas nitroxide-protein interactions could be easily measured with the (10,3)acyl-CoA and the (7,6)acyl-CoA, much less or even no significant interactions could be detected with the (5,10)acyl-CoA or the (1,14)acyl-CoA. (6) The above results suggest that spin-labeled long-chain acylCoA added to mitochondria binds by its polar moiety to the ADP carrier. The acyl chain interacts with the ADP carrier protein over a length of 10-15 A. The remaining portion of the acyl chain experiences a fluid lipid environment.


The amino acid sequence of a carboxypeptidase inhibitor from potatoes. The carboxypeptidase inhibitor from Russet Burbank potatoes (C. A. Ryan et al. (1974b), J. Biol. Chem 249, 5495) is a mixture of approximately equal amounts of two polypeptide chains containing 38 and 39 amino acid residues, respectively. The chains differ in their amino terminal sequence only, one beginning with smaller than Glu-His-Ala ... and the other with smaller than Glu-Gln-His-Ala ..... Specific cleavage procedures utilized in determining the complete amino acid sequence of the inhibitor included acid cleavage of the aspartyl-proline bond and tryptic and chymotryptic digestion. Mass spectrometry, automatic Edman degradation, and subtractive Edman degradation were employed in sequencing the resulting peptide fragments.


A calorimetric and monolayer investigation of the influence of ions on the thermodynamic properties of phosphatidylcholine. The effects of various ions and 2H2O on the thermal properties of phosphatidylcholine dispersions were studied using differential scanning calorimetry and the change in the surface potential of monolayers with temperature. The phosphatidylcholine in 2H2O dispersion exhibits a slightly higher transition temperature and lower enthalpy of melting than a phosphatidylcholine in H2O dispersion. Monovalent (H+, Na+, and Li+) and some divalent cations of chloride salts (Ba2+, Mg2+, and Sr2+) have no effect on the thermal properties of phosphatidylcholine, while halide salts of the di-positive ions Cd2+ and Ca2+ have an effect on both the enthalpy of melting and transition temperature. No effect attributable to the metal ion was observed in non-halide salts of cadmium. The chloride salt of La3+ has no effect on lipid thermal properties whereas that of Fe3+ affects the transition temperature. The enthalpy of melting of phosphatidylcholine in one molar solutions of potassium salts increases in the order: CNS minus greater than acetate greater than I minus. Such large, polarizable anions clearly interact with phosphatidylcholine and must therefore also confer a negative charge on the lipid. The potassium salt of SO4-2 minus has no effect. Possible origins of the observed trends are discussed.


Differential solubilization of proteins, phospholipids, free and esterified cholesterol of rat liver cellular membranes by sodium deoxycholate. 1. Smooth microsomes, Golgi-rich fractions, and light and heavy plasmalemmal subfractions from rat liver were isolated and their purity assessed using enzymic, chemical and morphological criteria. 2. Membranes were prepared by Tris-EDTA washing combined with sonication treatment of the different subcellular fractions. 3. Washed membranes were submitted to differential solubilization with 0.26% sodium deoxycholate. When the deoxycholate/phospholipid molar ratio (R) is raised, all the membranes showed a maximum protein solubilization occurring at R approximately equal TO 2. The higher the membrane neutral lipid to phospholipid molar ratio is, the lower the solubilized protein plateau lies. 4. Phospholipids are solubilized in slightly greater amounts than proteins and their solubilization is complete at R equals 14-16. 5. For R smaller than 2, sterols are solubilized in slightly greater amounts than phospholipids. At maximum protein solubilization, cholesterol and cholesterol esters completely differ in their behaviour. The whole membrane cholesterol goes into solution for R equals 14-16 while the solubilization of esterified cholesterol is never complete. The higher the protein plateau is, the lower the cholesterol esters solubilization curve asymptote lies.


Interaction of different forms of haemoglobin with artificial lipid membranes. The action of different forms of haemoglobin (oxy-, carboxy-and methaemoglobin) and myoglobin on the leakage of Rb+ out of liposomes has been investigated. The results presented will demonstrate that only methaemoglobin is particularly effective in interacting with phospholipid vesicles by changing their permeability and catalyzing a peroxidation of their unsaturated hydrocarbon chains.


Partial purification and characterization of the antidiuretic hormone-inactivating enzyme from renal plasma membranes. An antidiuretic hormone-inactivating peptidase located in renal plasma membranes of porcine kidney medulla has been studied. Treatment of antidiuretic hormone (lysine vasopressin) with renal plasma membranes resulted in a progressive loss of biological activity as measured by the rat pressor assay. The reaction of 2,4,6-trinitrobenzenesulfonic acid with released amino groups was employed to follow the peptidase-catalyzed hydrolysis of the hormone. An 83-fold purification of the membrane-bound peptidase was achieved by Lubrol PX solubilization of the membranes followed by DEAE-cellulose, hydroxylopatite, and 8% agarose column chromatography. The molecular weight of the peptidase was 442 000 as determined by 8% agarose gel filtration. An analysis of the antidiuretic hormone hydrolysis products by thin-layer chromatography revealed the presence of trinitrophenyl-glycinamide. The release of glycinamide from the hormone as a function of time was demonstrated. Mg2+ had a slight inhibitory effect and Ca2+ had a strong inhibitory effect on the peptidase activity.


Guanine aminohydrolase in rat and mouse red cells: a potent inhibitor of guanylation of tRNA. 1. The red blood cells of mice and rats contained guanine aminohydrolase (EC 3.5.4.3). This enzyme was not present in rabbit, sheep or human red blood cells. 2. The enzyme from rat blood cells was separated into two activities by column chromatography on DEAE-cellulose. Both isozymes were labile but it was possible to show that the more abundant enzyme followed Michaelis-Menten kinetics, had an apparent Km of 4.0-10-6 M and was not activated by GTP nor inhibited by allantoin. 3. We believe, therefore, that guanine aminohydrolase was the protein in rat and mouse red blood cells that inhibited the enzyme (in rabbit reticulocytes) responsible for guanylation of tRNA.


Active site directed effectors of allosteric enzymes. This communication introduces the concept of an active site directed effector, in terms of the two state model of Monod et al. (Monod, J., Wyman, J. and Changeux, J.-P. (1965) J. Mol. Biol. 12, 88-118), a consideration made necessary by the observation that the activity of a number of enzymes of the control type is modulated by effector molecules whose structure is similar to that of the substrate. We present equations which describe the kinetic responses obtained in its absence; this seemingly paradoxical activation, at low (S), is not tions the v versus (S) plot obtained in the presence of the effector crosses that obtained in its absence; this seemingly paradoxial activation, at low (S), is not explainable by the other frequently used two state models (Monod, J., Wyman, J. and Changeux, J.-P. (1965) J. Mol. Biol. 12, 88-118; Rubin, M.M. and Changeux, J.-P. (1966) J. Mol. Biol. 21, 265-274; Frieden, C. (1967) J. Biol. Chem. 242, 4045-4052; Dalziel, K. (1968) FEBS Lett. 1, 346-348 and Nichol, L.W., O'Dea, K. and Baghurst, P.A. (1972) J. Theor. Biol. 34, 255-263). The model is discussed using examples taken from the literature and successfully used to reanalyse published data on the enzyme deoxythymidine diphosphate D-glucose pyrophosphorylase (Frieden, C. (1967) J. Biol. Chem. 242, 4045-4052).


Substrate-induced redox change of selenium in glutathione peroxidase studied by x-ray photoelectron spectroscopy. Glutathione peroxidase showed an X-ray photoelectron spectroscopy signal of the Se 3d (3/2, 5/2) electrons at 54.4 eV. After the addition of the acceptor substrate H2O2, a marked shift of this signal to a value of 58.0 eV was observed. Upon subsequent treatment with the donor substrate glutathione, this chemical shift was reversed and the original signal was obtained. These data demonstrate that the enzyme-bound selenium moiety participates in the catalytic process. From the chemical shift obtained it is concluded that the enzyme shuttles between a selenol or selenol derivative in its reduced form and a seleninyl or selenonyl compound in its oxidized form.


Organophosphate inhibitors: the reactions of bis(p-nitrophenyl) methyl phosphate with liver carboxylesterases and alpha-chymotrypsin. Bis(p-nitrophenyl) methyl phosphate (BNMP) has been tested as a spectrophotometric titrant for a group of serine hydrolases. Bis(p-nitrophenyl) methyl phosphate reacts rapidly with liver carboxylesterases from chicken, sheep, and horse, and more slowly with alpha-chymotrypsin, releasing 2 mol of p-nitrophenol per active site titrated, and producing a phosphorylated enzyme very stable to dephosphorylation. However, pig liver carboxylesterase produces 2.2 mol of p-nitrophenol per active site titratedmreaction of pig and chicken liver carboxylesterases with bis(p-nitrophenyl) [3H]methyl [32P]phosphate clarified this differencemone molecule of the chicken enzyme reacts with one molecule of bis(p-nitrophenyl) methyl phosphate, releasing both p-nitrophenol residues, and resulting in an inhibited enzyme with one phosphorus atom and one methyl group covalently bound. Pig enzyme reacts rapidly, forming (presumably) methyl p-nitrophenyl phosphoryl-carboxylesterasemthis further reacts, concurrently producing methyl phosphoryl-carboxylesterase plus p-nitrophenol, or free enzyme plus methyl p-nitrophenyl phosphate, in the ratio of about 5 : 1 at pH 7.55. The free enzyme produced undergoes further reaction with bis(p-nitrophenyl) methyl phosphate until all the carboxylesterase is inhibited.


Chorismate mutase of Chlamydomonas reinhardi. Partial purification and some properties. Chorismate mutase (chorismate pyruvatemutase, EC 5.4.99.5) was extracted from Chlamydomonas reinhardi by sonication. Fractionation of crude sonic extracts with (NH4)2SO4 and by DEAE-cellulose and Sephadex gel chromatography indicated a single peak of chorismate mutase activity with molecular weight 61 000. The Michaelis constant for 20-fold purified enzyme was 0.46 mM. Prephenate dehydrogenase (EC 1.3.1.9) and prephenate dehydratase (EC 4.2.1.40) activities were not detected in our crude or partially purified preparations of chorismate mutase. Tyrosine (1.25 mM) inhibited chorismate mutase activity by approx. 85% in crude and partially purified preparations. Phenylalanine (1.25 mM) inhibited 20%. Tryptophan (1.25 mM) by itself had no detectable effect on chorismate mutase activity but it completely reversed inhibition by tyrosine and phenylalanine. No repression of chorismate mutase was observed when the minimal growth medium was supplemented with aromatic end products.


Naja melanoleuca (forest cobra) venom. Purification and some properties of phospholipases A. Three phospholipases A (Fractions DE-I, DE-II and DE-III) were purified from Naja melanoleuca (Forest cobra) venom by a combination of gel filtration on Sephadex G-50 and chromatography on DEAE-cellulosemthe purified phospholipases A were homogeneous by various physicochemical criteria. Whereas Fraction DE-I contains 118 amino acid residues, Fractions DE-II and DE-III comprise 119 residues. The three enzymes are cross-linked by seven disulphide bridges, have asparagine as N-terminal amino acid and the C-terminal is glutamic acid or glutamine. The molecular weights of the three phospholipases A from sedimentation analysis at pH 2.1, also by the sodium dodecylsulphate-gel method and calculated from the amino acid composition, were close to 13 000. Studies of circular dichroism in the spectral region between 195 to 305 nm showed that the three phospholipases A contain similar helical contents but revealed conformational differences between their side-chain chromophores.