[Prognosis and treatment of bacterial endocarditis. Review of 70 cases]. The long term results of medical and surgical treatments have been reviewed in 70 cases examined during the last 8 years. In 24 of them, bacterial endocarditis developed after valvular replacement. Antibiotic treatment was administered during at least 6 weeks. Determinations of the minimum inhibitory concentration of the antibiotic and of the bactericidal power of the serum were considered as the most important laboratory controls. In the post-operative cases with prosthetic valves, numerous pathogenic organisms were found, including gram (minus) bacilli and monilia, which may partly account for the high mortality in this group. Despite surgical reinterventions, 20 of the 24 patients died. For the gram (+) cocci, prognosis is however statistically worse (at the 99% confidence limit) when prosthetic valves are present. Out of the 46 patients without prosthetic valves, 31 (68%) had a favourable bacteriological and haemodynamic evolution; in this group, gram (minus) bacilli and monilia were never found to be the pathogenic organisms. For streptococci infections, recovery was obtained in 73% of the cases (24 out of 33). Percentages of long term recovery are very similar in mitral (67%) and aortic (69%) valvular involvment, but the frequency of surgical indication was very different in either group. In cases of aortic valvular disease, valvular replacement was indicated for bacteriological or haemodynamic reasons in 19 of the 20 patients who recovered. Amongst the 9 patients who died, 6 were not operated upon. Valvular replacement is by far less frequently necessary in cases of bacterial endocarditis on the mitral valve : one prosthetic valve amongst 8 patients who recovered. Finally, the authors discuss the place of surgery in the treatment of bacterial endocarditis. According to their experience, recent improvement in the prognosis of the disease seems to depend more on the surgical approach of the problem than on the discovery of new antibiotics.


Electronic processes in generation of nerve excitation. In a frog sciatic nerve stained by very dilute solution of eosin (0.1 mumol/1 minus to 100 mumol/1) and illuminated with a rather intensive light (10,000--100,000 lux), a single electric stimulus elicited not a single response, but a train of spikes. Latency time and reversibility of the effect, threshold concentration, threshold illumination, frequency and full length of train of spikes were investigated in detail. The results of the experiments are in agreement with the theory according to which the generation of action potentials involves electronic processes.


Selective coronary arteriography.

Selective coronary arteriography. A series of 414 selective coronary arteriographies in 322 patients has been done at Ullevål Hospital from May 1971 to Jan. 1974. Judkins technique was used in all cases. The indications for arteriography, the diagnoses as regards the coronary arteries, the therapeutic consequences,and the complications of selective coronary arteriography are described.


Aortocoronary vein bypass in patients with angina pectoris. In the 3-year period from May 1971 to April 1974, 90 patients had aortocoronary bypass for angina pectoris at Ulleval Hospital. One patient died shortly after the operation (operative mortality 1.1%). There were no further deaths in the observation period. Clinical improvement was seen in 93% of the patients, early shunt patency in 92%. The study suggests that patients with isolated affection of the right coronary artery should not have bypass, because these patients 1) had less severe symptoms, 2) had better preserved left ventricular function, and 3) seemed to have a smaller chance of benefiting from the operation than the other patients. Multiple shunts gave good clinical results and carried no higher surgical risk than did single shunts. Good clinical results were seen also in patients with occluded shunts provided they had at least one patent shunt too. Graft occlusion occurred early and was associated with low graft flow as measured intraoperatively. Graft occlusion was not usually followed by demonstrable myocardial necrosis. In view of the small operative risk and the high score of symptom relief it is concluded that all patients with angina pectoris that does not readily respond to medical treatment, should be considered for aortocoronary bypass.


Inhibition spectra of the human pancreatic endopeptidases. The present work describes the effect of seven naturally occurring proteinase inhibitors on the human pancreatic endopeptidases cationic trypsin, anionic trypsin, chymotrypsin I, chymotrypsin II, and protease E (an elastase-like protease). The inhibitors tested in order of their decreasing effectiveness were alpha-1-proteinase inhibitor (alpha-1-antitrypsin), lima bean trypsin inhibitor, soybean trypsin inhibitor, Bowman-Birk (soybean) inhibitor, Kunitz pancreatic trypsin inhibitor, porcine Kazal inhibitor, and chicken ovomucoid. The human trypsins demonstrated a higher degree of susceptibility to these inhibitors than did the chymotrypsins while human protease E showed remarkably little inhibition by any of these naturally occurring proteinase inhibitors except for alpha-1-proteinase inhibitor. The contribution of each of these proteolytic enzymes to the total proteolytic activity of crude extracts was also investigated using specific active-site directed reagents. These studies revealed that the trypsins constituted approximately 35% of the proteolytic activity while the chymotrypsins represent approximately 32% of the total proteolytic activity. Human protease E and possibly human pancreatic elastase are responsible for approximately 21% of this activity as measured on crude pancreatic extracts.


Partial antibiotic therapy in Haemophilus infuenzae meningitis. Its effect on cerebrospinal fluid abnormalities. To examine the influence of partial antibiotic therapy on laboratory findings in Haemophilus influenzae meningitis, 272 untreated cases and 202 partially treated, culture-positive cases from 1953 through 1971 were reviewed. There was no significant difference between the two groups with respect to several cerebrospinal fluid (CSF) values. Both the untreated and partially treated groups had a similar proportion of cases with negative Gram stain and CSF glucose level over 40 mg/100 ml or a predominance of CSF mononuclear cells. Eight patients had received ampicillin sodium, chloramphenicol, or tetracycline for two days or more. The CSF findings of these patients resembled those of the untreated group. The data support the conclusion that antibiotics in the usual outpatient dosages seldom interfere with the diagnosis of H influenzae meningitis.


Clinical experiences with colonoscopy. A review of 100 cases. Our experience with 100 colonoscopic examinations are described. The clinical value of the procedure is outlined and the minimal degree of attendant morbidity, when performed by a competent endoscopist, are emphasized. The indications and contraindications for this relatively recently devised diagnostic and therapeutic modality should be commonly known. The procedure should be done whenever indicated.


Increase in IgM-bearing lymphocytes in peripheral blood of pregnant women. Lymphocytes from peripheral blood of pregnant women were studied with the use of markers for membrane-bound immunoglobulins (B cells) and receptors for sheep erythrocytes (T cells). It was found that there was a significant increase in the number of IgM-bearing lymphocytes during pregnancy. This returned to normal levels after parturition.


Eosinophilic gastroenteritis with malabsorption, extensive villous atrophy, recurrent hemorrhage and chronic pulmonary fibrosis. A patient with diffuse eosinophilic gastroenteritis, associated with progressive chronic interstitial pulmonary fibrosis, was followed for 29 years.  His major symptoms were recurrent gastrointestinal bleeding, anemia, diarrhea, malabsorption,  and increasing respiratory insufficiency.  Multiple jejunal biopsies revealed eosinophilic infiltration and extensive villous atrophy.  Results of a lung biopsy and pulmonary function tests were consistent with chronic interstitial pulmonary fibrosis.  His gastrointestinal symptoms responded to steroid therapy, but he died of progressive respiratory insufficiency.  At autopsy, villous atrophy was noted to extend throughout the whole extent of the small intestine in association with multiple "pseudopolypoidal" inflammatory lesions.


Contractures in partially depolarized muscle treated with caffeine or nitrate. Frog toe muscles partially depolarized with a subcontracture concentration (15 or 20mM) of K+ rapidly developed tension when exposed to 1 mM caffeine, which alone did not cause contracture. This action resulted from a lowering of the mechanical threshold by the caffeine and thus was similar to that caused by replacement of Cl- with NO3-. Maximal tension was the same in the caffeine and NO3- media but took much longer to develop in the former. Equilibrating the muscles with caffeine for 60 s (the time calculated for complete diffusion) did not reduce contraction time significantly. However, prolonging the exposure of muscles to caffeine beyond this time enhanced the drug's capacity to potentiate both the twitch and 30 mM K+ contractures and shortened the contraction time of the contractures. Toe muscles that had undergone a contracture in 100 mM K+ and were recovering in 15 mM K+-Ringer generated tension in the presence of 1 mM caffeine or NO3- but only after enough repolarization had been achieved so that a response to a second challenge with 100 mM K+ could be demonstrated. Although prolonged immersion in the K+-enriched recovery solution caused a disappearance of sensitivity to a test depolarization, addition of 1 mM caffeine or replacement of Cl- with NO3- promptly evoked a contracture. These results imply a reversible step in the recovery process that is both potential and time dependent. Since application of 5 mM caffeine to either normally polarized or depolarized muscles always immediately causes contracture, more than one site of action for caffeine is indicated. After disruption of the transverse tubules, partially depolarized muscles showed no response to NO3- or 1 mM caffeine but contracted vigorously when exposed to 5 mM caffeine.


Acid-induced excitation of afferent cardiac sympathetic nerve fibers. The effect of acids on activity of afferent sympathetic nerve fibers from the left ventricle has been examined. Action potentials were derived from the upper thoracic communicating rami of the left side of anesthetized dogs. Application of a solution of lactic acid to the left ventricular surface caused excitation in both myelinated and unmyelinated fibers. The minimum concentration required for excitation was 7.5-75 mug/ml for the unmyelinated fibers and 375-750 mug/ml for the myelinated fibers. Excitation of the unmyelinated fibers induced by coronary occlusion was suppressed by pretreatment with sodium bicarbonate, 500 mg/kg. However, excitation of the myelinated fibers was influenced little by the agent. Pretreatment with a large dose of Trasylol failed to suppress excitation induced by coronary occlusion. The result suggests that acidosis plays a role in excitation of the unmyelinated fibers induced by myocardial ischemia, but not in excitation of the myelinated fibers.


Freeze-fracture analysis of junctional complexes in human ciliary epithelia. The junctions connecting the epithelial cells of the human ciliary body were studied on replicas of freeze-fractured preparations. Gap junctions are present at the lateral surfaces of the cells of the pigmented epithelium. Gap junctions, isolated linear strands and desmosomes are found between the apical surfaces of pigmented and non-pigmented epithelial cells. Gap junctions, zonulae occludentes and desmosomes join the lateral surfaces of the non-pigmented epithelial cells. These findings suggest that the blood-aqueous barrier is located at the level of the zonulae occludentes of the non-pigmented epithelial cells. This is consistent with previous studies using thin sections and tracer substances. The function of the many gap junctions connecting the cells of the two epithelial layers is obscure since their presence is not consistent with electrophysiological data from this region.


Carbohydrate metabolism of the lens depending on age. V. Problems of mathematical approach and graphical presentation. For investigations on age-dependent changes of lens metabolism, longitudinal studies are requisite. Graphic representation of such findings should be based on a proper arithmetic age scale. Using the lens weight for representing the age leads to distortion of the curves, whereby certain periods of life are liable to be overemphasized. In longitudinal studies, data on concentrations should never be given per unit weight, but rather for the whole lens. Absolute values of the whole, intact lens may be referred to a reference value, a percental representation of the curves is possible. With regard to the expectancy of life of test animals one may already state that longitudinal studies including the senile phase will only be feasible with rats.


[Selective atrophy of the radial peripapillary capillaries and visual field defects in glaucoma (author's transl)]. The existence and distribution of atrophic radial peripapillary capillaries in 33 autopsy eyes of patients with chronic glaucoma or different optic nerve atrophies are compared with their visual field defects and stage of atrophy or excavation of the disc. No correlation of defective RPC and visual field defects was found. The selective atrophy of RPC is therefore supposed to be secondary to different atrophies of the disc.


[The course of zonular fiber. A further electronenmicroscopic study (author's transl)]. Zonular fibers could be shown between the basement membrane of the pigmented epithelium of pars plana and the elastic tissue of Bruch's membrane. A connection of zonular fibrils between the unpigmented epithelium and the basement membrane of pigmented epithelium of the pars plana could not be observed. It is possible to discuss two independent courses of zonular fibers.


[The electro-oculogram in the early postoperative period following fistulizing operations (author's transl)]. EOGs were obtained from 2 groups of patients suffering from glaucoma chronicum simplex the day before surgery and 3, 5, 8, 11 and 14 days after trephining or fistulizing operation after Scheie. Though and peak potentials of the treated eyes were significantly less than those of the untreated fellow eyes five days after surgery. In addition on the 11. postoperative day after Scheie a second potential decrease was seen. The EOG-changes observed appear to reflect disturbances of the choroidal circulation after fistulizing operations.


Development of beaks of Rana pipiens larvae. Rana pipiens larval beaks of consist of column cells, sheath cells and basal cells which supply cells to column and sheath. Each column consists of disk-like precone cells, cone cells and keratinized cone cells; they are cells in different stages of the process of keratinization. Breaks first appear externally at embryonic stage 24. Epidermal cells align at the tip of the jaw at stage 21. They increase in number and change in shape. Keratinization starts at stage 23. By stage 24, the apical column cells are keratinized and the histological organization is set for the whole larval period. During the larval period, the numbers of column cells increase until stages VIII or IV, stay relatively constant during mid-larval stages, and decrease at late larval stages. The beak is completely shed at stage XX. The widening of the beaks goes on during the entire larval period. Along the cutting edge of the jaw the tooth spikes increase in number and in individual width as the animal grows older and larger. Thyroid hormone causes a premature reduction of the column cell number and a precocious beak loss. The loss of break at metamorphic climax is thyroid dependent event.


Postoperative respiratory effects of morphine and halothane anesthesia: a study in patients undergoing cardiac surgery. Lung volumes, deadspace, ventilation, and ventilatory response to CO2 challenge were studied on the day before and for the first three days after corrective cardiac surgery. Ten patients underwent coronary artery bypass grafting and ten patients had mitral valve prostheses inserted. Half of the patients in each group received halothane as the major anesthetic, and the other half received morphine sulfate (1-2 mg/kg). Mitral valve-replacement patients anesthetized with morphine showed lower CO2 sensitivity on the first postoperative day than those who received halothane. Patients who had coronary artery bypass grafts tended to hyperventilate during the postoperative period, but this did not occur on the first postoperative day in those who received morphine anesthesia. Respiratory rate was always higher postoperatively, most markedly in patients who receivedhalothane for coronary artery bypass grafts. Vital capacity was diminished by 67 per cent in all groups postoperatively. VD/VT tended to increase during the first and second postoperative days and then decrease toward control values on the third postoperative day in all groups except valve-replacement patients who received morphine. Morphine anesthesia may increase the period of mechanical ventilation necessary after cardiac surgery partly as a result of impaired CO2 sensitivity.


Factors of delayed hypersensitity in pulmonary tuberculosis. In a study of delayed hypersensitivity in 54 patients with pulmonary tuberculosis who were on specific treatment, 33 patients could not be sensitized to dinitrochlorobenzene (DNCB) although 25 of these were tuberculin (PPD) positive. The majority of the patients also had positive skin reactions to another recall antigen, streptokinase-streptodornase. To exclude a drug effect on DNCB reactivity, 40 untreated patients were studied. Twenty-six (65 per cent) of these did not show DNCB reactivity. The cause for nonsensitization to DNCB was not clear. There was no abnormality in the number of T lymphocytes in the peripheral blood of 28 patients.


Effect of halothane on isometric twitch and tetanus response and the associated heat production in striated muscle of frogs. The purpose of these investigations was to determine the effect of halothane on isometric contraction of striated muscle and to measure the associated heat production. This basic information is necessary before studies more directly relating to malignant hyperthermia are undertaken. Sartorius muscles were isolate from Rana pipiens during winter and summer months. It appears from these experiments that there is a prolongation of the relaxation phase of the twitch and tetanus responses with low concentrations of halothane, with a more diffuse effect on the contractile process evident at higher administered concentrations. The results of heat measurements, using a sensitive thermopile-galvanometer system, are compatible with the hypotheses that this effect on relaxation could result from either an interference with calcium reuptake by the sarcoplasmic reticulum or an increased affinity of the troponintropomyosin complex for available calcium.


On the "easy bruising" syndrome with normal platelet count. A study of 75 patients. Seventy-five consecutive patients with normal platelet counts were investigated for "easy bruising." All had a normal coagulation profile, and all except four were women. None were on aspirin or other antiplatelet agents. Two specific groups could be delineated. In type I (44 patients, mean age, 35), platelet function was normal to supranormal. Megathrombocyte number was elevated in 60% of patients and correlated with the presence of antiplatelet antibody in 30% of patients. In type II (31 patients, mean age, 34), platelet function was abnormal: impaired epinephrine aggregation (primary and secondary wave) in 97%, impaired connective tissue aggregation in 77%, and impaired ADP aggregation in 42%. Megathrombocyte number was elevated in 71%, and antiplatelet antibody was present in 38% of patients. The "easy bruising" syndrome can be differentiated into two categories: type I, in which a platelet abnormality is unlikely, and type II, in which a platelet abnormality exists. Elevated incidence of antiplatelet antibody in both groups suggests  a possible autoimmune cause.


Solar retinopathy and foveomacular retinitis. The visual disturbances caused by looking into the sun or a solar eclipse have been known for many years. Recently, there have been discussions about whether or not solar retinopathy is a distinct clinical entity or identical to the disease termed foveomacular retinitis. A series of 36 patients has been evaluated at Letterman Army Medical Center with the ophthalmoscopic appearance compatible with both conditions in various stages of the disease. By use of clinical history, funduscopy, visual fields, Amsler Grid, color acuity testing, color fundus photography, and fluorescein dye studies, it is our distinct impression that these two conditions are identical.


Trisomy 4p in a family with A t(4;15).

Trisomy 4p in a family with A t(4;15). This report concerns a trisomy 4p in a mentally retarded girl with multiple congenital anomalies. A translocation between chromsomes Nos. 4 and 15 was discovered in three generations of the patient's pedigree.


[Ultrastructure study on the whole chromosome in radiation induced anomalies: II. Re-arrangements and fragments]. Chromosome aberrations induced by 500 rads gamma ray irradiation (dicentrics, rings, and fragments) were observed at the ultrastructural level using the "whole mount" technique. The area of chromatid rejoining could not be demonstrated. The pairing of fragments observed could be explained by the perisistence of interchromatid fibers.


[Partial 14q trisomy. I. Partial 14q trisomy by maternal translocation t(10;14) (p15.2;q22)]. A balanced reciprocal translocation t(10;14)(p15.2;q22) is present in the mother and the maternal grand mother of two boys. One, with a normal phenotype, received the balanced translocation, the other, exhibiting congenital malformations, is trisomic for the proximal part of 14q.


[Partial trisomy 14q II.--Partial trisomy 14q due to a maternal t(12; 14) (q24.4; q21)]. The phenotype of an 18-month-old male infant trisomic for the proximal portion of the long arm of chromosome 14 was reported and compared with that of previously reported cases. For the identification of the resulting syndrome, the most consistent features are psychomotor and growth retardation, and an oval, dysmorphic facies which includes a distinctive form of the mouth and a prominent nose. The trisomy in the child reported here is due to a familial translocation transmitted by the mother and present in at least three generations: t(12;14)(q24.4;q21). The 12q duplication in the child's genome is minimal and does not seem to have contributed to his phenotype.


Trisomy iop. A report of two cases due to a familial translocation rcp (10;21) (pII;pII). Trisomy for the short arm of chromosome number 10 was diagnosed (by a G-banding method) in two sisters with multiple congenital defects. Their mother and two other sisters showed a balanced translocation 46,XX rcp(10;21)(p11;p11), so the affected girls were the result of a maternal adjacent-1 meiotic segregation with a karyotype 46,XX, der(21), rcp(10;21)(p11;p11)mat. The concordant features in the abnormal patients constitute the following syndrome: severe psychomotor retardation, congenital microsomatia, mild hydrocephalus with cranium-face disproportion, low set ears with hypoplastic helix, ocular colobomata, pulmonary stenosis,flexion deformity of wrists and elbows, bilateral fifth finger clinodactyly and simian creases, hypoplastic dermal ridges, bilateral talipes, persistent icterus and delayed bone age. The phenotypical and cytogenetic findings permit the individualization of the 10p trisomy.


[Interstitial deletion of the long arm of one 11 chromosome]. A case of in testitial deletion of the long arm of chromosome 11 associated with mild facial deformity, broad skull and mental retardation is reported.


[Partial 7q trisomy].

[Partial 7q trisomy]. A 17-month old boy is partially trisomic for 7q22 and 7q31 due to a probable insertion in the paternal chromosome 13. The phenotype of the patient is similar to that of two other patients reported in the literature.


[Mosaic 14 trisomy in a female child with multiple abnormalities]. Chromosomal preparations obtained from lymphocytes and fibroblasts revealed a minor clone, 47,XX,+14, in a female newborn with multiple malformations. Other types of rearrangement of chromosome 14 are discussed.


Centrally-mediated cardiovascular effects of 5-hydroxytryptophan in MAO-inhibited dogs: modification by autonomic antagonists. In MAO-inhibited dogs, 5-hydroxytryptophan (5-HTP), either 5 or 10 mg/kg i.v., caused hypotension with variable effects on heart rate. Reflex responses to bilateral carotid artery occlusion (BCO) were greatly inhibited by 5-HTP. The hypotensive effects were markedly inhibited by cerebral and extracerebral decarboxylase inhibition with RO 4-4602 and the inhibition of BCO was delayed. Selective extracerebral decarboxylase inhibitation with MK 486 did not prevent either the hypotensive action of 5-HTP or the effect on BCO, although the amino acid now consistently caused bradycardia. Left ventricular pressure and dP/dt were reduced, but cardiac output was maintained by an increase in stroke volume. Hypotension was due predominantly to decreased peripheral resistance. The hypotensive action of 5-HTP was abolished or greatly attenuated after pretreatment with either yohimbine or methysergide, but was unaffected by haloperidol. These results indicate that cerebral decarboxylation and formation of 5-HT are responsible for the hypotension after 5-HTP in MAO inhibited dogs.


Regulation of C3-enzymes in facultative phototrophic bacteria: the cold-labile pyruvate kinase of Rhodopseudomonas sphaeroides. Pyruvate kinase (EC2.7.1.40) from Rhodopseudomonas sphaeroides was purified 40-fold be precipitation with protamine sulfate and ammonium sulfate followed by gel-filtration. The preparations obtained from cells grown with different carbon sources or cultural conditions differ with respect to specific activity but not with respect to molecular weight (250000 dalton) or regulatory properties. The phosphoenolpyruvate (PEP)-saturation cruve of the enzyme is sigmoidal with Hill coefficients varying from nH equals 1.8 (pH 9.2) to 2.7 (pH 6.0). The enzyme is activated by adenosinemonophosphate (AMP) and the sugarmonophosphates ribose-5-phosphate (R-5-P), glucose-6-phosphate (G-6-P), and-to a lesser extent-fructose-6-phosphate (F-6-P). Fructose-1.6-bisphosphate (FDP) has no measurable effect. Inhibitors of the enzyme are adenosinetriphosphate (ATP), inorganic phosphate (Pi) and the dicarboxylic acids succinate and fumarate. Kinetic analysis reveals that the sugar-phosphates and the dicarboxylic acids act as true allosteric ligands, whereas the effects of AMP, ATP, and Pi cannot be interpreted soley in terms of allosteric interactions. Cold-treatment of the enzymes lead to a rapid loss of activity, but does not change the regulatory properties of the enzyme. Analysis of the kinetics of cold-inactivation and its reversal at 30 percent C, together with studies on the gelfiltration behaviour of the native and the cold-treated enzyme make it likely that the cold-induced loss of activity is due to a dissociation of the enzyme.


[Percutaneous stimulation of sensitive peripheral nerves in acute crises of essential trigeminal neuralgia]. The electric stimulation of sensitive peripheric fibres has been used with good results in the control of pain. It is belived that the modern theory of pain phisiology offers scientific basis to explain its action mechanism. This method was applied to twenty-one patients suffering from trigeminalgia, being continually stimulated during thirty minutes with variable voltages, according to the affected region. As a result, it was obtained the immediate relief of pain for periods of time varying from six and forty-eight hours.


[Hereditary multiple exostosis with spinal cord compression]. A case of hereditary multiple exostoses successfully operated is reported. The patient, a 15 year-old white brazilian boy, was admitted with tetraplegia and Babinski's sign. Early diagnosis followed by prompt surgery may prevent permanent spinal cord damage.


Anesthesia of the ear by iontophoresis of lidocaine. Anesthesia of the tympanic membrane and ear canal by the use of iontophoresis of local anesthetics is a painless and safe method of anesthesia for office myringotomy and polyethylene tube insertion, and possibly for surgical use as well.  With the use of guinea pig models, the introduction of 4% lidocaine hydrochloride solution in the middle ear space with iontophoresis revealed no toxic effects on the eighth nerve, and epinephrine hydrocloride potentiates the effects of lidocaine and has no protective mechanism on the eighth nerve function.


Trisomy 18.  A temporal bone report.

Trisomy 18.  A temporal bone report. Since Edwards first described the trisomy 17-18 syndrome in 1960, the findings in the temporal bones of only four patients with this condition have been reported.  They varied widely, ranging from a normal temporal bone, to severe malformations of both the middle and inner ear structures.  This study describes the temporal bone findings in a patient with this syndrome.  Many of the abnormalities described previously were present as well as the following unreported findings: complete bony atresia of the external canal, an aberrant tensor tympani muscle that did not insert into the malleus but rather attached to a dehiscent area in the Fallopian canal, wide short utricular and saccular ducts, and a widely patent cochlear aqueduct.  There was also a developmental arrest of the membranous structures within the cochlea that probably occurred during the 12th week of fetal life.


Incidence of vestibular symptomatology in 2,500 U.S. Navy diving accidents (1933-1970). The U.S. Navy diving accident records of 2,500 cases for the years 1933 to 1970 were analyzed and sorted into Type I and Type II decompression sickness. Type II was further sorted into "vestibular" and "other" categories. It was concluded that Type II symptoms accounted for 30% of the decompression accidents and it was estimated that the overall incidence of vestibular symptomatology was between 10 and 20%. Nearly 30% of the Type II cases were diagnosed as having vestibular involvement, although almost 60% of the cases contained a report of a symptom typically associated with the vestibular system complex, e.g., dizziness and nausea.


Antihypertensive drug therapy in USAF flying personnel. The reviewed data concerns hypertensive USAF aircrew members, as available from the WAVR File (July 1973) and the records of the Aeromedical Consultation Service at USAFSAM (1 July 1972-30 June 1973). Of over 6,500 entries in the WAVR File, hypertension was listed as a diagnosis for 754 individuals. Drug therapy had been instituted in 379 cases (50.3%) of the total. Statistics regarding ranks, age groups, and aeronautical ratings are presented. The group included 520 pilots, of whom 268 were receiving drug therapy. Associated medical conditions, e.g., abnormal EKG findings, carbohydrate intolerance, and hyperuriciemia, are presented. Similar data are reviewed for the 84 patients evaluated on the Aeromedical Consultation Service (USAFSAM).


[Effect of the protease inhibitor aprotinin on pulmonary function and on the inhibitory activity of sputum in patients with chronic obstructive bronchitis]. It has been investigated whether a substitution of protease inhibitor deficiency is indicated in case of chronic obstructive airway disease. As a therapeutic possibility, apronitin isolated from bovine organs (tyasylol), which in vitro inhibits sputum proteases up to 80 per cent was tested. Besides infusion, inhalation was chosen for application by which a protease inhibition could be attained. We observed an inhibition of the course of illness associated with a good tolerance of the preparation. Whether a therapy applying the addition of protease inhibitor is reasonable in the long run in chronic diseases cannot yet be concluded from these investigations.


A possible alternate pathway of bacteriochlorophyll biosynthesis in a mutant of Rhodopseudomonas sphaeroides. A previously uncharacterized bacteriochlorophyll-less mutant (mutant 8) of Rhodopseudomonas sphaeroides has been found to excrete a tetrapyrrole-protein complex into the incubation medium. The structure of the major pigment of the complex was characterized as 2-desacetyl-2-vinylbacteriopheophorbide. The corresponding magnesium derivative does not fit into the currently proposed biosynthetic pathway for bacteriochlorophyll, and thus may indicate the existence of an alternate pathway of bacteriochlorophyll synthesis in this organism. Such an alternate pathway would be possible if reduction from the chlorin to the tetrahydroporphyrin stage can occur either before or after hydration of the 2-vinyl substituent of chlorophyllide a to an alpha-hydroxyethyl group.


Effect of strong illumination on the ion efflux from the isolated discs of frog photoreceptors. (1) Low levels of illumination do not modify the efflux of the radioisotopes 22Na, 86Rb, 36Cl, and 45Ca from the isolated discs of the photoreceptors of the frog (Rana Catesbeiana). (2) The effluxes of 22Na+, 86Rb+ and 36Cl- increase when the discs are illuminated with more than 10(4) erg/cm2 per s for a few minutes. There is no effect on the efflux of 45Ca2+ or of [14C]urea. (3) The effect is greater for monochromatic lights of wavelengths in the shorter region of the spectrum. (4) The effect is also present in bleached visual membranes.


Osmotically induced electrical changes in isolated bullfrog small intestine. 1. Steady state values of cell water, intracellular Na+ and K+ concentrations, and the electrical parameters ETr, Em, and Isc in the mucosa of isolated bullfrog small intestine were determined following immersion in sodium sulfate Ringer solutions with identical ionic composition but different osmolalities. 2. Cell water and intracellular K+ concentration were inversely related to the osmolality of the bathing medium. During 1 h immersion, intracellular Na+ concentration was not significantly affected by an increase or decrease in external osmolality. 3. Replacement of a hypotonic or an approximately isotonic (normal) medium by a medium of greater osmolality caused statistically significant decreases in ETr, Isc and the (inside negative) magnitude of Em. Conversely, when a hypertonic or a normal medium was replaced by one of lower osmolality, significant increases in the magnitude of these parameters were observed. 4. An equivalent circuit model for the epithelial cell layer, in which the resistance of a relatively highly conducting extracellular shunt pathway is assumed to be the major determinant of the electrical responses of the small intestine to external osmolality, has been shown to account satisfactorily for the observed changes in ETr and Em. In terms of this model, the experimentally observed dependence of Isc on external osmolality requires that, even when both the mucosal and the serosal sides of the tissue are bathed by identical media, isolated bullfrog small intestine maintains a finite diffusion potential across the shunt pathway. This is consistent with current views concerning transepithelial ionic transfer mechanisms.


B lymphocytes in primary and secondary deficiencies of humoral immunity. The quantitative studies of B lymphocytes in peripheral blood have been performed in various forms of primary and secondary immunodeficiency disease in man. X-linked agammaglobulinemia was found to comprise two sub-types, one lacking B-cell population, the other showing low numbers of B lymphocytes. The absence of B cells in severe combined immunodeficiency was corrected by marrow transplants in 3 children. Cases of DiGeorge syndrome and lepromatous leprosy showed an absolute increase in numbers of B lymphocytes in peripheral blood, probably a compensatory mechanism in the market deficit of T-cell population and function. The reconstitution of DiGeorge syndrome by fetal thymus transplant reversed the abnormally high percentage of B lymphocytes.


[Photochromism of visual pigments. I. Formation of isochrome products during reversible transformations of frog rhodopsin]. Reversible phototransformations of rhodopsin of the frog in vitro (in digitonine extracts) at -22 degrees C under the effect of light with gamma 579 and 435 nm are reversible processes. However, while heating photogeneration product, besides true rhodopsin, thermo-unstable form is (pseudorhodopsin) is revealed. It owes its name due to the similarity of its spectral properties and photosensitivity with rhodopsin. At temperatures higher than -22 degrees C the reversibility of the system is disturbed. The nature of pseudorhodopsin is discussed.


Thymus transplants: a look to the future. In a review of thymus transplants performed in a variety of immunodeficiency syndromes, results in the DiGeorge syndrome seen uniformly successful. Rapid restoration of lymphocyte responsibility in vitro and achievement of normal peripheral blood lymphocyte counts are characteristic. In nearly all other types of isolated thymic deficiency or combined immunodeficiency there has been only transient or meager restitution and more often than not complete failure. A few exceptions were noted in a combined immunodeficiency state and in two cases of isolated T-cell deficiency. The use of transfer factor may have played an important adjunctive role. Future attempts must depend upon more precise characterization of the defects, utilizing attempts to define subpopulations of T and B cells; consideration of HL-A restrictions; methods of implantation and use of adjunctive measures (eg thymosin) or other cell populations (such as liver or spleen).


Transfer factor I: methods of therapy.

Transfer factor I: methods of therapy. Transfer factor was first discovered by Lawrence in 1955, but was not used therapeutically until 1969 when we reported its use in a Wiskott-Aldrich patient. Since that time, it has been used in a wide variety of disorders related to defects in cellular immunity, infectious diseases, and malignant diseases. This report describes our experience with transfer factor. Report number I discusses rationale for patient selection, procedures for transfer factor therapy, procedures for monitoring the efficacy of therapy, untoward effects of therapy, and experience with transfer factor therapy in severe combined dual system deficiency disorder. The results of our study on transfer factor therapy indicate that it is capable of inducing a clinically acceptable level of cell-mediated immunity in approximately 50% of patients with a variety of immunodeficiency disorders. It also appears to be a useful adjunct to chemotherapy, and may possibly act synergistically with transplanted fetal thymocytes to produce a constantly regenerating specifically competent source of T lymphocytes, thereby obviating the need for bone marrow transplant for severe combined dual system deficiency disorder.


Studies of the human factor VIII/von Willebrand's factor protein. II. Identification and characterization of the von Willebrand protein. The purified factor VIII-related protein we have previously characterized from normal cryoprecipitate possesses both procoagulant activity and vWf activity. We have attempted to isolate and characterize this protein from three patients with severe vWd. This protein is absent or markedly diminished in amount in these vWd patients, as judged by gel filtration, polyacrylamide-gel electrophoresis, and immunoprecipitation assays. Likewise, the procoagulant and vWf activities are deficient. As vWf activity is one of the major biologic functions of either the normal or hemophilic factor VIII-related protein, the purified protein should be designated the f VIII/vWf protein.


Specificity of bovine thrombin and reptilase for mammalian plasmas. The effect of bovine thrombin and reptilase was investigated on plasmas of ten species of five vertebrate classes. It was established that both enzymes have an expressed specificity for mammalian plasmas, however, their narrower species specificity is different. These comparative coagulation studies, their significance in the laboratory examination also contribute to the analysis of evolution of clotting factors.


Kinetics of agonist conductance changes during hyperolarization at frog endplates. The effect of rapid hyperpolarization on acetylcholine- or carbachol-induced currents was studied at voltage clamped frog endplates. Following a hyperpolarizing step the agonist-induced conductance increased approximately exponentially to a new level. The rate constant for this process was smaller during hyperpolarization or lowered temperature, and was also smaller for acetylcholine than for carbachol. The results are interpreted in terms of a potential-dependent conformational change of the receptor.


A prospective study of acute pancreatitis. All 78 patients with acute pancreatitis admitted to one hospital in a 2-year period were included in a prospective survey of conservative management. The overall mortality rate was 11.5 per cent, being 46 per cent for 11 patients subjected to early laparotomy and only 6 per cent for patients managed without operation. Twenty-six patients were considered to have severe acute pancreatitis and all 9 deaths occurred in this group. Biliary disease was present in 51 per cent of patients, and the majority of those with biliary disease were over 60 years old. Alcohol-related acute pancreatitis occurred in 26 per cent of the total patients, and none of this group was over 60 years old. Acute pancreatitis was considered idiopathic in origin in only 13 per cent of the patients. Elective biliary surgery in 30 patients resulted in freedom from recurrent attacks of acute pancreatitis for the follow-up period (12-30 months). The results compare favourably with those in which glucagon and high dosage aprotinin (Trasylol) have been utilized in the management of acute pancreatitis.


Routine assay for detection of IgG and IgM antiglobulins in seronegative and seropositive rheumatoid arthritis. A convenient technique suitable for the routine estimation of IgM and IgG antiglobulins has been devised. The assay involves the binding of antiglobulins (rheumatoid factors) to rabbit immunoglobulin linked to the surface of plastic tubes; the amount of antiglobulin bound is then determined by adding radiolabelled antihuman IgG or IgM. Both antiglobulins were raised in virtually all seropositive rheumatoid arthritics, and 19 out of 22 seronegative patients had raised values for either IgM or IgG rheumatoid factors. The test should prove valuable in diagnosis and the results further emphasize autosensitization to IgG as a dominant immunological characteristic of different forms of rheumatoid arthritis.


Uveitis: report of a 10-year survey in Northern Finland. In order to determine the distribution of etiologic and diagnostic categories of uveitis at the Oulu University Eye Hospital, 653 patients with uveitis treated during the years 1964-1974 were reviewed. Of the 653 patients, 321 were men and 332 women; 547 had anterior, 64 posterior and 42 generalzied uveitis; 524 unilateral and 129 bilateral; 570 acute and 83 chronic; and 446 single and 207 recurrent. The etiologic factors were distributed into rheumatoid (7.2%), streptococcal (4.1%), tuberculosis (3.7%), toxoplasmosis (3.3%), varicella-zoster (1.7%), sarcoidosis (1.4%), staphylococcal (1.1%), leptospirosis (0.6%), lymphatic leucemia (0.5%), herpes simplex (0.5%), yersinosis (0.1%) and undetermined cases (75.8%). There were no cases of syphilis. Most of the cases in this series were anterior and acute uveitis occurring mainly in the age group 20-59 years.


Ventricular obstruction due to ectasia of the internal carotid artery. This is a report of the first recorded instance of ventricular obstruction at the foramen of Monro by an ectatic carotid artery. The clinical course, investigations and treatment are described.


Optimal conditions for the growth of malignant human and animal cell populations in immunosuppressed mice. Immunosuppressed mice have been used to support the growth of xenogeneic human and animal malignant cell populations. The optimal conditions for tumor growth are neonatal thymectomy coupled with antithymocyte serum or thymectomy, followed by whole-body irradiation and bone marrow reconstitution. When mice are inoculated with a mixture of normal and malignant cells, the malignant cells have a selective advantage. No such selectivity is found when the mixed populations are grown in vitro. Human tumors may also be grown in immunosuppressed mice. These tumors retain the organization of the original tumor in the human host. The advantages of this system to cancer researchers are discussed.


Results of graft surgery for coronary artery disease: a progress report. Coronary artery surgery is here to stay, but it will continue to be influenced by accumulating experience and evolving techniques. Direct internal mammary-to-coronary artery anastomoses offer the hope for improved results in certain patients. Tissue-compatible prosthetic grafts could be developed and offer an alternative in selected patients. Improved microsurgical techniques may permit broader applications with multiple grafts to smaller branches in patients with more diffuse disease. We are continually reminded, however, that surgical treatment is palliative, and that most of these patients will ultimately die of their disease. Thus the search for a better understanding of the arteriosclerotic process and improved methods for altering the course of the disease becomes more important than ever.


The fine structure of the iris of the grass frog, Rana pipiens. The iris of the grass frog Rana iiens, can respond to light even when isolated from the remainder of the animal. The iris is a three-layered structure, comprising a stromal layer and two layers of pigment epithelium. The sphincter pupillae, which is composed of pigmented smooth muscle cells, is embedded between the two layers of pigment epithelium. There is no dilator pupillae in this species. We have been unable to find any cells or any organelles in the iris which are anatomically specialized for photoreception in any obvious way.


A possible functional relationship between the subcommissural organ and the pineal complex and lateral eyes in Rana esculenta and Rana temporaria. In previous publications (Diederen, 1972, 1973) evidence was presented that light and darkness hardly influence the secretory activity of the subcommissural organ (SCO) in intact frogs, i.e. frogs in which all photo-receptive organs are present. In the present study the influence of long daily photoperiods and of continuous darkness on the SCO of frogs in which the frontal organ, the pineal organ and the eyes were eliminated separately or in combination was studied. The parameters used to measure the secretory activity of the SCO were the amount of aldehyde-fuchsin(AF)-positive material in the SCO cells, the incorporation of 35S-cysteine by the SCO cells and the growth rate of Reissner's fibre (RF). Only in frogs in which the eyes as well as the entire pineal complex were eliminated was an unequivocal influence of light and darkness on the secretory activity of the SCO demonstrable: in blinded frogs without a pineal complex, the growth rate of RF is clearly enhanced in animals exposed to light. If the eyes or the pineal complex or the pineal organ alone have not been eliminated, then the stimulatory influence of light on the growth rate of RF can no longer be detected. This indicates that light causes the pineal complex and the eyes to exert an inhibitory influence on the secretory activity of the SCO. The hypothesis is put forward that in intact frogs influences of light on the secretory activity of the SCO, at least so far as the production of RF is concerned, are prevented by the photo-receptive organs. In this way a functional relationship between the SCO on the one hand and the pineal complex and eyes on the other hand may be expressed. A mechanism by which the influences of light on the SCO may be prevented by the pineal complex and the eyes is suggested.


Morphological definition of thymocyte subpopulations. An attempt was made to distinguish immature from mature, immunocompetent thymocytes in the adult mouse using morphological criteria.  All procedures enriching for competent thymocytes also enrich small cells whose morphology is very similar to the small thymocytes that have been described in the medulla of the thymus (Abe and Ito, 1970).  A heterogeneity of competent thymocytes is likely since the enriched populations always contain a number of medium sized cells.  These latter cells show spontaneous DNA-synthetic activity and are probably the source of thymus proliferative activity.  Owing to their characteristic morphology these two cell types might represent the precursors for each of the two differentiated T cell types that have been found to occur in delayed type hypersensitivity (Matter, 1974).


A monoamine in the gustatory cell of the frog's taste organ: a fluorescence histochemical and electron microscopic study. Fluorescence histochemistry reveals that in the frog's taste organ a yellow fluorescence is regularly observed at the most basal region of the sensory epithelium. The fluorescence has a strong intensity, but it fades rapidly upon the UV-irradiation. The peak of the emission spectrum is at 520 mmug. Following reserpine treatment the yellow fluroescence is markedly reduced, but not depleted completely. From these characteristics the monoamine fluorescence is regarded as representing 5-HT (serotonin). The ultrastructural study on sensory epithelia shows that the terminal portions of gustatory cell processes are localized at the basal region. These portions are filled with dense cored vesicles (700-1000 angstrom in diameter) and frequently opposed with nerve fibers penetrating into the epithelium. The gustatory cell processes are also interposed between the terminal portions of nerve fibers. The cytoplasm of the gustatory cell process is characterized by many mitochondria, fine filaments and glycogen particles, but contains few cored vesicles. The distribution of terminal portions of gustary cell processes seems to correspond fairly well to that of the monoamine fluorescence observed discontinuously along the basal lamina. Accordingly it is concluded that the fluorigenic monoamine is localized in the cored vesicles of the gustatory cell.


Scanning electron microscopy of the wall of the third ventricle of the brain of Rana temporia. II. Electron microscopy of the ventricular surface of the pars ventralis of the tuber cinereum. Scanning electrom microscopy of the ventricular surface of the pars ventralis of the tuber cinereum of the frog Rana temporaria shows that it can be divided in (1) a dorsolateral area, characterized by the presence of very numerous large, solid, bulbous protrusions (2) a medial area, where the large bulbous structures are completely absent and which is diffusely covered with very numerous cilia, (3) a transiotional area located between the two other regions. The large bulbs, shown by scanning electron microscopy, correspond with the end-bulbs of thick ventricular dendrites of nerve cells revealed by transmission electron microscopy. At least many of these intra-ventricular bulbs are dendritic endings of peptidergic neurosecretory neurons, which have been tentatively identified as adenohypophysiotropic neuro-hormone producing neurons (Derickx et al., 1972, 1973a, 1973b). The structural features of the dendritic endings plead in favour of a possible receptive role.


Electron microscopic studies of the lung of the frog. II. Topography of the inner surface by scanning and transmission electron microscopy. Scanning and transmission electron microscopy were used to study the inner architecture of the frog lung. In some specimens the alveolar surface mucus layer was removed to permit the examination of underlying features. The inner surface of the frog's lung is covered by a layer of microvilli belonging to only one type of epithelial cells. The boundaries of these epithelial cells are demarcated by small ridges. Different degrees of lung expansion cause variations of the surface topography. The morphology of certain surface features is examined in detail. Several methods of drying the specimens are compared.


Ultrastructure of the neurohemal hypothalamic floor of the frog, Rana catesbeiana. The fine structure of the hypothalamic floor was studied in the frog, Rana catesbeiana. The regions slightly anterior and posterior to thw swollen hypothalamic floor part, which has been classically designated as the median eminence, contained neurosecretory axon terminals abutting on the capillary walls. The region relatively far anterior to the swollen part did not show neurosecretory axons terminating on capillary walls. The neural stalk contiguous to the rostral border of the pars intermedia had few neurosecretory axon terminals which end on the terminal portions of the ependymal processes covering the capillary wall. The functional significance of the regional differentiation of the frog neurohypophysis is discussed in connection with the regional differentiation of various secretory cells in the adenohypophysis.


Abnormal left ventricular wall motion at mid-ejection in patients with coronary heart disease. The degree of inward motion at mid-ejection was examined for seven segments on the silhouettes of left ventriculograms taken in the 30 degrees RAO projection in patients with normal coronary arteries. The pattern of wall motion described in these patients was used to distinguish abnormalities in mid-systolic wall motion. One or more abnormally contracting segments were found at mid-ejection of 27 of 42 patients with obstructive coronary artery disease and normal end-systolic wall motion. Of the 57 segments found in these patients, 41 or 72% corresponded to sites of significant coronary artery obstruction. Seven patients had electrocardiographic evidence of prior infarction. Following coronary graft surgery in eight patients improved motion was found in association with graft patency in seven priviously delayed segments and two new areas of delayed wall motion associated with nonpatent grafts and electrocardiographic changes of infarction appeared. We postulate that some of the myocardial fibers in late contracting segments have been injured or infarcted and are able to contract effectively only during the latter half of ejection when ventricular wall tension is reduced.


Main left coronary artery disease. Clinical experience from 1964-1974. Obstructive lesions of the main left coronary artery (LCA) were demonstrated angiographically in 73 patients, comprising 4.3% of the total population referred to us for diagnostic evaluation of chest pain. Although there were no specific historical or clinical features which could absolutely distinguish this subgroup from the larger population of coronary artery disease patients, 81% (34/42) of the double Master's exercise tests, in which the patient achieved a heart rate of at least 110 beats/min. demonstrated greater than or equal 2 mm R-ST segmental depression. Of the total group of 73, 32 were evaluated during the six-year period from 1964 to 1971 and a preliminary report made in 1972. The diagnosis in the remaining 41 patients was established in the 1/2 year period from 1971 to 1973. The initial 32 patients were seen before the significance of a main LCA lesion was appreciated. In this subgroup there were five deaths at the time of cardiac catheterization. However, in the more recent group improved recognition of patients with possible main LCA disease prior to catheterization has led to a much lower death rate related to diagnostic catheterization. Only one of the last 41 patients undergoing coronary angiography has died. Nineteen patients were managed medically. Of this group 17 were considered to be under the same risk of death as the surgical candidates. Their mortality rate, as high. The risk of hying was 43.6% after 24 months, 51.1% after 36 months, and 73.6% after 42 months of observation. Although the initial surgical experience, using internal mammary artery implants and saphenous venin bypass grafts, was associated with a high mortality, direct revascularization surgery over the last 2 1/2 years has been accomplished with a perioperative mortality of only 6.2%. All deaths in the group of 40 patients receiving elective revasularization with saphenous vein bypass grafts occurred in the first six months following surgery. The risk of dying was 12.5% after six months of observation and was unchanged for the remainder of the follow-up period. After 21 months the difference in survival between the two groups is statistically significant (P less than 0.05). The one late death among the surgical survivors occurred four months after the operative procedure and was related to noncardiovaxcular surgical complications. The surgical survivors have been followed for an average of 27 months. Thus revascularization surgery has improved the prognosis for patients with main LCA disease. We currently advise prompt evaluation for any patient suspected of having this type of obstruction and urgent idrect revascularization surgery if this lesion is demonstrated angiographically.


Inhibition of kinin formation by a kallikrein inhibitor during extracorporeal circulation in open-heart surgery. Involvement of the kinin system was studied in 58 patients during extracorporeal circulation in open heart surgery. At the onset of extracorporeal circulation, there was no increase of free kinin in blood and no reduction of plasma kininogen, when the latter was expressed as mug bradykinin/mg plasma protein. With the lapse of time, kinin in the blood increased significantly, and decrease of kininogen was also significant. The longer the circulation time, the greater the consumption of kininogen. The site of the kinin formation was presumed to be the heart-lung machine since the level of kinin increased slightly and kininogen decreased gradually in the blood leaving the machine, compared with those levels entering the machine. The difference in kininogen was significantly different from zero at termination of extracorporeal circulation. Administration of a kallikrein-trypsin inhibitor, trasylol (A. G. Bayer), infused into the heart-lung machine, prevented the decrease of kininogen. Reduction of the total peripheral resistance during this circulation was also prevented. The hemoconcentration, presumably the result of vascular permeability increase caused by increased kinin, was prevented by trasylol in cases in which extracorporeal circulation lasted over 60 minutes. Trasylol applied thus appears to be an effective counteragent for circulatory disturbances which occur during extracorporeal circulation.


On the inhibition of elastase by serum. Some distinguishing properties of alpha1-antitrypsin and alpha2-macroglobulin. 1. The influence of serum on the elastolytic and esterolytic activity of elastase has been studied. With both substrates the inhibition curves are linear. 1 ml of normal human serum inhibits the activity of 0.77 mg of pure porcine elastase. 2. Elastase binds faster with alpha2-macroglobulin (k = 3.4-10(6) M-1 S-1) than it does with alpha1-antitrypsin (k = 5-10(5) M-1 S-1). 3. The dissociation constant of the alpha-antitrypsin -elastase complex is much lower than that of the alpha2-macroglobulin-elastase complex but both complexes are very stable (Ki less than 10(-10) M). 4. Protein pi (inter-alpha-inhibitor) does not inhibit elastase.


Fibre-optic endoscopy and radiology in the investigation of the ipper gastrointestinatract. A comparative study is reported of endoscopy and the barium meal in the investigation of the oesophagus, stomach and duodenum, based on 281 endoscopies. There was total agreement between the two methods in 239 instances, including 101 normals, 80 peptic ulcers and nine cancers. In nine instances with unequivocal follow-up information there was definite disagreement, radiology being wrong in two (incorrect confident diagnoses of carcinoma) and endoscopy being wrong in seven (three carcinomas and four ulcers not diagnosed). Of 116 normal barium meals, 15 definite abnormalities were demonstrated by endoscopy, including six peptic ulcers. 'Probable' radiological diagnoses were confirmed by endoscopy in 44 instances. In those where endoscopy disagreed, radiology was definitely shown to be wrong in five, and endoscopy in five. A high degree of accuracy can be achieved by the selected use of both techniques, the information obtained from each considered of equal importance, and neither being regarded as the final arbiter.


Familial Kallmann syndrome with unilateral renal aplasia. On the basis of studies in two brothers and their double first cousin, the Kallmann syndrome (KS) is discussed as an X-linked syndrome of anosmic hypogonadotropic hypogonadism. The anosmia is thought to represent agenesis or hypoplasia of the olfactory lobes, the mildest form of the alobar holoprosencephaly developmental field defect; this is supported by the finding of hypotelorism in two of the patients and their mother. The endocrine defect is thought to represent a hypothalamic abnormality of the luteinizing hormone releasing hormone; borderline normal intelligence may represent another pleio-tropic CNS manifestation of the KS gene. All three affected males had unilateral renal aplasia, associated in one with ipsilateral absence of the testis. The presence of at least two developmental field defects (involving the CNS and urogenital system) makes it likely that the KS is a true multiple congenital anomaly syndrome; this is supported by the finding of additional, mostly minor, anomalies reported by other investigators. Heterozygous females may also show manifestations of anosmia, hypogonadism, possibly even internal genital malformation; however, genetic heterogeneity of anosmic hypogonadism is possible, and for the time being it is probably better to designate sporadic female cases of anosmic hypogonadism as examples of the olfacto-genital syndrome of DeMorsier. Linkage studies are urgently needed to clear up the question of genetic heterogeneity and to help develop empiric recurrence risk figures in anosmic hypogonadism.


Adrenal weight and catecholamine content in renal and calciferol-induced hypertension in rabbits. 1. Hypertension was produced in rabbits by unilateral renal encapsulation combined with contralateral nephrectomy or by the administration of calciferol and calcium lactate. 2. Weighed post mortem, the adrenal glands from the two hypertensive groups were significantly heavier than those from normotensive animals of similar weight. There was a direct correlation between the adrenal gland weight and the mean arterial blood pressure measured at the time of the terminal experiment. 3. The catecholamine content of the adrenal glands from the two groups of hypertensive animals was similar to that of the normotensive animals. 4. There was histological evidence of adrenal cortical hypertrophy in the glands of the hypertensive groups of animals.


The pace of patient processing in the mental health system. In consultation to some mental health agencies, we have found the pace and quality of patient processing to be needlessly labored, discontinuous, and often redundant. Processing is too often "for the record" rather than "for the client." Information rarely flows comprehensively, comprehensibly, or continuously between the evaluating system and the system from which the client is sent or to which he is referred. Contributing factors are identified and analyzed; the processing system is demystified. A change in strategy is suggested.


Fixed dose prostaglandin E2 tablets in the induction of labour in multipara. Prostaglandin E2 tablets in a dose of 0.5 mg. hourly were administered to 40 multiparous patients for induction of labour following amniotomy. Thirty-seven patients delivered vaginally within 18 hours, with a mean amniotomy delivery interval of 7 hours 53 minutes. The advantages of this method of administration are discussed and side-effects reported.


Continuous negative chest-wall pressure as therapy for severe respiratory distress in older children. Continuous negative chest-wall pressure (CNP) was used to treat five children, 4 to 11 years of age, who had progressively severe respiratory distress caused by Pneumocystis carinii penumonitis. After initial improvement, two patients developed progressive increases in respiratory rate, alveolar-arterial oxygen gradient, intrapulmonary right-to-left shunt, and hypoxia. The disease ended fatally in both. The remaining three patients continued to improve and recovered from their pulmonary disease. These results show that CNP therapy provides an effective means of improving arterial oxygenation in spontaneously breathing older children, just as in neonates, without the need for endotracheal intubation, prolonged sedation, and muscle relaxants.


Acetylation rates and monthly liver function tests during one year of isoniazid preventive therapy. A blind, prospective evaluation of the incidence and course of isoniazid-associated liver injury was made in 358 hospitalized men. The men were psychiatric patients during one year of tuberculosis preventive therapy. Blood samples were obtained at monthly intervals from the patients, the majority of whom were taking isoniazid. When the data were analyzed at the end of the year, a strikingly increased incidence of abnormal serum transaminase (SGOT) and bilirubin values was found among the isoniazid recipients. However, most subjects demonstrating biochemical evidence of hepatic injury recovered completely while continuing to take isoniazid and did not progress to clinically overt hepatitis. The mechanism underlying this adaptation to isoniazid injury is unknown. No serum antibodies against isoniazid could be demonstrated, and no correlation was found between the presence of antinuclear antibodies or elevated isoniazid plasma concentrations and the occurrence of hepatic injury. These data support the view that hepatotoxic metabolities of isoniazid may be responsible for the liver injury.


Ionic aspects of excitation in rod outer segments. The current status of the problem of ionic mechanisms underlying excitation of vertebrate photoreceptors is reviewed. Evidence is presented that the ionic dark current of retinal rods is sustained by the action of a ouabain-sensitive Na-K exchange pump driven by oxidative metabolism. The photoreceptors are depleted of K when the pump is stopped by ouabain. Considerations of cell membrane topology, kinetics of the light response, and signal amplification indicate that the light-induced suppression of the ionic dark current is mediated by a diffusible internal chemical transmitter substance. The desensitizing effect of low CA2+ Ringer's on the light responses of vertebrate rods, along with other indirect evidence, suggests that the transmitter substance may be calcium ions released from the internal membranous disks of the outer segments.


Surface carbohydrate composition of different types of chicken lymphocytes. A simple and quick procedure was used to analyse the carbohydrate composition of surface glycoproteins from chicken lymphocytes. The procedure included papain digestion of the cells, a two-step purification of the supernatant material and a sugar analysis by gaschromatography. The method made it possible to analyse samples of about 10(9) lymphocytes. The surface glycoproteins from different chicken lymphocyte preparations were found to differ significantly in their sugar composition. Lymphocytes from thymus, bursa, spleen or blood were characterized by typical relative amounts of glucose, galactosamine, fucose and sialic acid. The values for mannose, glucosamine and galactose, however, were approximately 1:1:1 for all four lymphocyte preparations. Bursectomy or thymectomy in combination with whole body irradiation altered the carbohydrate composition significantly. The results suggest the possibility that the carbohydrate composition can be used as a marker for different lymphocyte populations. The results are also discussed in respect to the hypothesis that carbohydrate determinants on the cell surface determine the migration of lymphocytes.


Idiopathic orthostatic hypotension. Biochemical and pathologic observations in 2 cases. Two cases of idiopathic orthostatic hypotension are reported, one associated with striato-nigral degeneration (case 1) and the other with Lewy body parkinsonism (case 2). In case 1, cerebrospinal fluid monoamine studies were carried out before and during treatment with 5-HTP and L-dopa. Low values of 5-HIAA appeared to be associated with degeneration of the spinal cord intermediolateral column. L-dopa had a beneficial effect on both parkinsonism and hypotension over a period of 6 months. New pathologic observations included changes in the sacral cord and a topographically related involvement of the substantia nigra and striatum, consistent with recent experimental neuroanatomical data.


Coronary arteriographic appearances in patients with left anterior hemiblock. 24 of 163 consecutive patients (14.7%) undergoing selective coronary arteriography were found to have electrocardiographic evidence of left anterior hemiblock. 3 patients (2 of whom had alcoholic cardiomyopathy) had normal coronary arteries, 15 patients had triple vessel disease, 3 patients had double vessel disease, and 3 patients had single vessel disease. 18 patients (75%) had moderate to severe left ventricular enlargement as estimated by left ventriculogram. Comparison of these angiographic findings with those of 88 patients with normal intraventricular conduction showed the distribution of the coronary artery disease to be essentially similar in the two groups but that significant left ventricular enlargement was at least three times more frequent in patients with left anterior hemiblock than in patients with normal intraventricular conduction. It is suggested that the development of left anterior hemiblock depends more upon the presence of left ventricular enlargement than on the distribution of the coronary artery disease.


Mechanical and electrical causes for lack of frequency potentiation in normal patients, in coronary artery disease and in left bundle branch block. Nine atrial pacing (SP) runs and 8 ventricular pacing (VP) runs were carried out in patients without heart disease, and 10 AP runs in patients with coronary artery disease (CAD). For evaluation of myocardial contractility, the time derivative of left ventricular pressure (dpdt) was used. Comparing rest and AP at 155/min, AP in normal patients revealed a significant increase in dP/dtmax and a significant decrease in left ventricular end-diastolic pressure (LVEDP). This represents frequency potentiation. When comparing rest and VP values at 155/min in normal patients, no changes in dP/dtmax and LVEDP were seen. AP in patients with CAD demonstrated no change in dP/dtmax, but a decrease in LVEDP when compared to the rest values. dP/dtmin and left ventricular systolic pressure did not change in the 3 groups. VP, and even AP, in 2 additional patients with isolated left bundle branch block (LBBB) AND WITHOUt associated heart disease, revealed the same constellation of parameters as VP in normal patients. Our results show a lack of frequency potentiation in normal patients during VP and in patients with isolated LBBB during both AP and VP. It is concluded that the lack of frequency potentiation during AP in CAD is produced primarily by mechanical asynchrony of contraction, angiographically demonstrated as akinesia and dyskinesia. The lack of frequency potentiation in normal patients during VP and in patients with isolated LBBB due to asynchrony of activation resulting in asynchrony of contraction.


Unusual cholinergic response of bullfrog sympathetic ganglion cells. The membrane of bullfrog sympathetic ganglion cells was hyperpolarized by a direct action of ACh (more than 0.5 mM) in a solution containing both nicotine (0.24 mM) and atropine (0.14 mM). This ACh hyperpolarization could be imitated by neither carbachol nor bethanechol, suggesting that the ACh hyperpolarization was the response which was produced by a specific action of ACh, which appeared to be neither nicotinic nor muscarinic. The size of ACh hyperpolarization was increased during a conditioning hyperpolarization. The ACh hyperpolarization was completely blocked by ouabain (2 times 10(-3) mM) and eliminated in the Na-free lithium solution. These aspects of the ACh hyperpolarization suggested that generation of this hyperpolarization was associated with the sodium pump. The ACh hyperpolarization seemed to be partially responsible for the production of the slow IPSP, since a part of the slow IPSP remained occasionally in the presence of both nicotine and atropine.


Effects of glutamate and glutamic acid diethyl ester on the lobster muscle fibre and the frog spinal cord. The effect of bath applications of glutamic acid diethyl ester (GDE) and glutamate on the lobster muscle fibre and the from spinal cord were examined. In the lobster muscle fibre GDE (2 X 10(-3) M) did not antagonize the depolarizing action of glutamate (10(-4) M). In the frog spinal cord a small reduction in the excitatory effects of glutamate (10(-4)-10(-3) M) after GDE pretreatment was found only if the latter was given in very high doses (over 2 X 10(-3) M) which stimulated the neuronal firing. These observations show that GDE is not a specific antagonist of glutamate in these tissues.


Hydro-osmotic activity of "carba' analogues of oxytocin and [8-arginine] vasopressin on frog (Rana esculenta) bladder. The biological potency of neurohypophysial hormone analogues in stimulating water transport across the frog bladder (Rana esculenta) was estimated from the pD2 (negative logarithm of the peptide concentration eliciting 50% of its maximal hydroosmotic effect) and from the maximal response. Most analogues elicited maximal responses similar to those of the natural hormones. Both replacement of sulfur by a methylene group in the disulfide bridge and omission of the terminal amino group in oxytocin reduced hydroosmotic activity; carba substitution in oxytocin led to a greater drop in pD2 than the same substitution in deamino-oxytocin. On the contrary, the effects of substituting phenylalanine for tyrosine and of omitting the amino group were almost additive. Elimination of the carboxyl-terminal tripeptide sequence considerably reduced hydroosmotic potency; pressinamide was inactive up to 3 mug/ml. The highly potent antidiuretic peptides, deamino-[D-Arg8]vasopressin and deamino-6-carba-]D-Arg8]vasopressin, were weakly active in the hydroosmotic assay.


The origin of blood k-hydroxyindoleacetic acid following L-hydrazino-alpha-methyldopa (MK-486). Blood 5-HIAA-14C levels derived from exogenous D,L-5-HTP-14C were investigated in normal, sham-operated and nephrectomized rats pretreated with MK-486 and probenecid (200 mg/kg i.p.). Blood 5-HIAA-14C levels decreased in nephrectomized rats following probenecid. Peripheral decarboxylase inhibition by MK-486 was enhanced by both probenecid and nephrectomy. Increased penetration of 5-HTP into brain occurred following probenecid. The results indicate that following MK-486 about 20% of the blood 5-HIAA-14C derived from 5-HTP-14C in rats originates in the CNS.


The chloride-dependent depression by GABA in the frog spinal cord. Spontaneous activities from ventral and dorsal roots of the isolated perfused spinal cord of the bullfrog were inhibited by GABA. beta-Alanine showed a strong and glycine a weaker inhibitory effect. The inhibitory effect of GABA was markedly reduced in a chloride-free medium, whereas glycine and beta-alanine still showed an inhibitory effect similar to that seen in normal medium. Employing the sucrose-gap method, a marked depolarization in the dorsal root and a small but obvious hyperpolarization in the ventral root were found by the application of GABA. These results support the view that GABA is one of the transmitters involved in pre- and postsynaptic inhibition of the spinal cord. The postsynaptic hyperpolarizing effect of GABA on motoneurones would be caused directly through increased permeability of the membrane to chloride ion. The depolarizing effect of GABA on primary afferent terminals is discussed in connection with chloride dependency.


The origin of blood 5-hydroxyindoleacetic acid following L-hydrazine-alpha-methyldopa (MK-486). Blood 5-HIAA-14C levels derived from exogenous D,L-5-HTP-14C were investigated in normal, sham-operated and nephrectomized rats pretreated with MK-486 and probenecid (200 mg/kg i.p.). Blood 5-HIAA-14C levels decreased in nephrectomized rats following probenecid. Peripheral decarboxylase inhibition by MK-486 was enhanced by both probenecid and nephrectomy. Increased penetration of 5-HTP into brain occurred following probenecid. Thr results indicate that the following MK-486 about 20% of the blood 5-HIAA-14C derived from 5-HTP-14C in rats originates in the CNS.


The effect of aprotinin on the harmine-induced tremor in lymphostatic encephalopathic and normal rats. In normal and lymphostatic encephalopathic rats, aprotinin pretreatment alters the duration of the harmine tremor and the cerebral concentration of the alkaloid; low doses shorten the tremor and decrease the concentration, a high dose causes the opposite. Aprotinin may decrease or increase the blood-brain barrier permeability of harmine. Because the findings are similar in both groups of rats the blood-brain barrier for harmine is assumed to be intact in lymphostatic encephalopathy. However, sick rats possibly suffer from an impaired cerebral elimination of harmine.


Serotonergic and cholinergic mechanisms during disruption of approach and avoidance behavior. Injections of D,L-5-hydroxytryptophan (D,L-5-HTP) into pigeons and rats working on approach schedules produce a period of behavioral depression that is temporally correlated to increased levels of total serotonin (5-?HT) in the telencephalon and diencephalon. Administration of alpha-methyl-meta-tyrosine (alpha-MMT) also results in depressed responding; however, the temporal correlation is with decreased levels of total 5-HT in brain. Our hypothesis to explain these two apparent opposite biochemical states which result in similar behavioral disruptions is that in both cases more 5-HT is released within certain key serotonergic synapses mediating this behavior. Evidence from subcellular studies supports this concept. tnot only are the levels of 5-HT significantly higher in preparations of nerve endings isolated from the telencephalon and diencephalon of pigeons given injections of D,L-5-HTP, but in vitro studies also show that low concentrations of L-5-HTP significantly increased the release of radioactive 5-HT from serotonergic nerve endings. On the other hand, L-5-HTP in much higher concentrations had no effect on the release of labeled dopamine or norephinephrine. A major metabolite of alpha-MMT, alpha-methyl meta tyramine, also caused a significant increase in the release of labeled 5-?HT from similar preparations of nerve endings. Whereas serotonin appears to be involved in the disruption of approach behavior, another series of studies have indicated that acetylcholine may play a role in excitation during avoidance behavior. Behavioral excitation observed following administration of tetrabenazine 18 hr after iproniazid pretreatment to rats working on shock-avoidance schedules was temporally correlated with lowered levels of acetylcholine in the telencephalon. Pretreatment with 0.8 mg/kg of atropine blocked excitation whereas one-eight of this dose increased the duration. Excitation in these rats was shortened by 50% following bilateral septal lesions, which lowered brain acetylcholine levels. Mechanisms to explain these neurochemical correlates of behavior are discussed.


Cell-mediated immune reactivity to hepatitis B surface antigen in liver diseases. The cellular immune reactivity to hepatitis B surface antigen (HBsAg) was studied in patients with liver diseases using a purified preparation of HBsAg and the leukocyte-migration agarose test. Inhibition of leukocyte migration by HBsAg was found in all 9 patients in the acute phase of viral hepatitis but not during convalescence. HBsAg inhibited migration of leukocytes in only 1 of 15 patients with chronic persistent hepatitis, in none of 16 with chronic periportal hepatitis, and in 2 of 21 with nonhepatic liver diseases. In normal control subjects inhibition of migration was found only in 1 physician exposed to HBsAg. Similar but not identical results were obtained with HBsAg-positive serum used as antigen. In patients with chronic hepatitis there was no correlation between reactivity to HBsAg and the presence of autoantibodies or anti-HBs. While further investigations using other preparations of antigens associated with HBV (e.g., hepatitis B core antigen) may better clarify the role of hepatitis B virus in some liver diseases, the present investigations suggest that a reactivity to HBsAg in patients with acute viral hepatitis may indicate clearing of the antigen, whereas in patients with chronic hepatitis it may reflect a state of specific tolerance to this antigen.


Cell-mediated immunity to hepatitis B surface antigen in blood donors with persistent antigenaemia. Cellular immunity to the hepatitis B surface antigen (HBsAg) and a liver-specific lipoprotein was studied, using the leucocyte migration test, in 38 asymptomatic blood donors found to have HBsAg in the serum. Sensitization to HBsAg was found in 26% and was related to the presence of liver damage, being detected in 47% of those with elevated serum aspartate aminotransferase but in only 13% with normal enzyme levels. The frequency of sensitization to this antigen in those with chronic persistent or chronic aggressive hepatitis on biopsy was also higher than in those with unrelated or minimal changes. The findings using the liver-specific lipoprotein as antigen were similar and there was a correlation between the results obtained with this and the hapatitis B surface antigen. This study supports the hypothesis that a T-lymphocyte response to hepatitis B virus antigen can initiate an autoimmune reaction to antigens such as liver-specific lipoprotein on the hepatocyte surface, and that this reaction may be of importance in the production of chronic liver damage. In the absence of the T-cell response, the autoimmune reaction cannot occur and the virus is able to establish a harmless symbiotic union with the host.


Independent appearance of anti-thymocyte and anti-RNA antibodies in NZB/NZW F1 mice. NZB and NZB/NZW (B/W) mice were studied for natural thymocytoxic autoantibody(NTA) and antibody to reovirus RNA by cytotoxicity and radioimmunoassay respectively.NZB mice developed NTA by 2-3 months of age.  RNA antibodies appeared later if atall.  NTA and anti-RNA were present in B/W mice starting at 4-5 months and increased in frequency with age.  Either activity could appear first and could be present without the other.  Thus, all four possible patterns of autoantibody occurrence were found.  NTA and anti-RNA in 12-month B/W sera were separable by sucrose density gradient ultracentrifugation; NTA is a 19S IgM antibody whereas anti-RNA is 7S.


Mechanisms of corticosteroid action on lymphocyte subpopulations.  I. Redistribution of circulating T and b lymphocytes to the bone marrow. The effect of corticosteroid administration on the redistribution of sirculating lymphocytes was studied in the guinea-pig, since this species closely resembles man in its relative resistance to the lymphopenic effect of corticosteroids.  A single intravenous injection of hydrocortisone (either 10 mg or 100 mg/kg) caused a profound but transient lymphocytopenia which was maximal at 4 hours following injection, with a returnto normal counts by 24 hours.  There was a proportionately greater decrease in circulating T lymphocytes compared to B lymphocytes, although both populations were diminished.  Chronic cortisone acetate treatment (100 mg/kg subcutaneously for 7 days) caused a similiar pattern of lymphocytopenia except that it was sustained during the period of chronically elevated plasma cortisol levels. The lymphocytes remaining inthe circulation during the period of lymphocytopenia responded normally in vitro to the mitogens phytohemagglutinin, concanavalin A, and pokeweek mitogen.  There was very littleeffect of corticosteroid administration on the numbers, proportions, or mitogenic response of splenic lymphocytes.  There was a dramatic increase in the bone marrow of proportions and absolute numbers of lymphocytes bearing surface T-and B-cell markers, as well as a marked increase in response of bone marrow lymphocytes to mitogenic stimulation during the period of maximal circulating lymphocytopenia caused by the administration of corticosteroids, especially chronic cortisone acetate.  There was a preferential homing of reinfused -51Cr-labelled syngeneic peripheral blood lymphocytes to the bone marrow of corticosteroid-treated recipients.  These studies demonstrate aredistribution of circulating lymphocytes to the bone marrow during corticosteroid treatment, resulting in an increase in immunocompetence of this compartment, while the peripheral blood lymphocyte compartment is quantitatively immunosuppressed due to a lymphocytopenia.


The migratory behavior of T blasts to contact sensitivity reactions in activelyand passively sensitized mice. The arrival of cells from lymph nodes immunized with the contact sensitizing agents oxazolone and picryl chloride at ears challenged with these antigens was studied inmice using the technique of labelling with -51Cr.  An apparent specificity of arrival was seen because the immune cells transfered contact sensitivity passively, giving rise to an inflammatory response in the ear, to which a subpopulation of cells (T blasts) was non-specifically attracted.  It was also shown that there are at least two distinct populations of cells with the ability to move to inflammatory sites: the first, found in immunized lymph nodes, moves to contact sensitivity reactions in both actively and passively sensitized mice; the second, found in bone marrow and oil-induced peritoneal exudates, moves to contact sensitivity reactions in actively sensitized mice, whereas in passively sensitized mice, the arrival of these cells at contact sensitivity reaction is poor.  It is suggested that the ability of T blasts to move to sites of inflammation my be useful as an assay technique for contact sensitivity reactions.


Plasmid-linked ampicillin resistance in haempohilus influenza type b. Four ampicillin-resistant, beta-lactamase-producing strains of Haempohilus influenzae type b were examined for the presence of plasmid deoxyribonucleic acid (DNA). Three resistant strains contained a 30 x 10-6-dalton (30Mdal) plasmid and one resitant strain contained a 3-Mdal plasmid. The ampicillin-sensitive Haemophilus strains examined did not contain plasmid DNA. Transformation of a sensitive H. influenzae strain to ampicillin resistance with isolated plasmid DNA preparations revealed that the structural gene for beta-lactamase resided on both plasmid species. DNA-DNA hybridization studies showed that the 30-Mdal Haemophilus plasmid contained the ampicillin translocation DNA segment (TnA) found on some R-factors of enteric origin of the H. influenzae plasmids.


Rosette formation of pig T lymphocytes with sheep erythrocytes. The relationship of sheep RBC rosette formation to density of thymus and blood lymphocytes was investigated. Thymocyte density was unimodal and cells of all densities rosetted equally. Blood lymphocyte density was bimodal with most rosette-forming cells in the denser ficoll layers. Papain treatment of SRBC increases rosette formation with blood lymphocytes while apparently maintaining specificity of T cells.


Immune response to Trichinella spiralis in the rat. I. Development of cellular and humoral responses during chronic infection. The immune response of rats to infection with Trichinella spiralis was studied serially for more than 1 year. Initial antigen-specific cellular reactivity, assessed by the lymphocyte transformation response, developed in the draining mesenteric nodes 3 days after infection. After 1 week reactive lymphocytes were detectable in the spleen and circulating blood, but the more 'remote' peripheral nodes did not harbor antigen-reactive cells until late in the second week. Thereafter, the patterns of antigen-responsiveness varied among the different lymphoid pools, but in all cases a decline in reactivity was seen after the first month. Serum hemagglutinating and homocytotropic antibodies, detectable by the tenth day, reached their peaks after 1 month of infection. Hemagglutinating titers persisted for more than 1 year but homocytotropic antibody was lost over this period. Comparisons are drawn between the evolution of the natural infection and the development of the host's immune response.


The nature of the deoxyribonucleosides involved in the binding of carcinogenic hydrocarbons to the DNA of mouse embryo cells. The DNA of mouse embryo cells was specifically labelled in the purine moieties with (G(3)H)-deoxyadenosine or in the cytosine moieties with (5-(3)H)-deoxycytidine. These cells were then treated with 7-methylbenz (a) anthracene (7MBA) or benzo (a)-pyrene (B(a)P) and the DNA isolated, degraded and fractionated by LH20 Sephadex column chromatography. When the purines of the DNA were tritium-labelled, radioactive hydroccarbondeoxyribonucleoside products were obtained. No such products were found with deoxycytidine pre-labelled DNA. Contrary to an earlier suggestion, these results indicate that it is the purine moieties of DNA which react with the metabolically activated hydrocarbon derivative in vivo.


Differential regeneration of intestinal proliferative cells and cryptogenic cells after irradiation. A dose of 900 rad gamma-rays to mice reduces the number of cryptogenic cells (those capable of crypt regeneration) per small intestinal crypt from about 80 to about 2 per surviving crypt. The surviving cells repopulate the crypt, the estimated cell-number doubling-time being about 24 hours, and on the fourth day after irradiation their numbers are still slightly below normal. The regeneration patterns for cryptogenic and proliferative cells differ significantly over the first 4 days after irradiation. The numbers of proliferative cells fall initially and remain low while the cryptogenic cells are increasing in number. The low levels persist for the first 1-5--2 days, after which there is a rapid rise in proliferative cells per crypt with a significant overshoot on the third day and a peak on the fourth day. The number of proliferative cells per crypt in control animals is about twice the number of cryptogenic cells. This ratio is on average 12 after irradiation (days 1--4). These data add support to the hypothesis that the small intestinal crypts contain a sub-population of stem cells that are distinct from the proliferative cells.


Mechanisms of protection of gamma-irradiated bacteriophage lambda by proflavine. The protective effect of proflavine on gamma-irradiated bacteriophage lambda and its isolated DNA was investigated under conditions of predominantly indirect or direct effects. In both conditions addition of small amounts of the dye during irradiation of phage or DNA was shown to enhance their biological activity. Protection against indirect effects results probably from extensive scavenging of radioinduced water radicals within the medium. On the other hand the results obtained at minus 196 degrees C, with irradiated DNA-proflavine complexes, imply the existence of a long-range transfer of the primary radiation damage of DNA towards the intercalated molecules of proflavine. A mechanism for the protective effect of proflavine against the direct effect of ionizing radiation on biologically active DNA is suggested.


Comparsion of the oxygen-enhancement ratio for gamma-ray-induced double-strand breaks in the DNA of bacteriophage T7 as determined by two different methods of analysis. Bacteriophage T7 was irradiated in a protecting medium under nitrogen and oxygen with 60Co gamma-rays. Double-strand breaks were measured by sucrose-gradient sedimentation and by boundary-sedimentation analysis. Both methods showed that the presence of oxygen during irradiation enhanced the production of double-strand breaks. This is at variance with a recent report which suggests that boundary-sedimentation analysis does not show an effect of oxygen. The discrepancy must be ascribed to differences in interpretation of the sedimentation data.


Thermoluminescent properties of crystalline halogen substituted uracils. The thermoluminescent properties of crystalline uracil (U), and its halogen-substituted derivatives, 5 bromo-uracil (5BrU), 5 fluorouracil (5FU) and 5 iodo-uracil (5IU), have been investigated. The X-ray-induced thermoluminescent output increases in the order U less than 5 FU less than 5BrU less than 5IU. However, a reversed relationship is found for the U.V.-stimulated thermoluminescence. The thermoluminescence-emission spectra suggest that the same de-excitation process operates in all the halogen-substituted uracils, but the glow curves show that the charge-trapping characteristics are different for each material.


Some aspects of brain neurochemistry after intrauterine exposure to tritium. Rats were continuously exposed to tritiated water (0, 1, 10 and 100 muCi HTO/ml body water) from conception to birth. Calculated, cumulative whole-body doses to the embryo and foetus were approximately 0, 6-6, 66 and 660 rad. The levels of several enzymes and established or presumptive central nervous system neurotransmitters were examined postnatally in whole brains. These were norepinephrine (NE), dopamine (DA), acetylcholinesterase (AChE) and monoamine oxidase (MAO). Intrauterine exposures to doses as low as 66 rad produced measurable and persistent decreases in brain weight and increases in NE concentrations at 21 and 45 days postnatally. No differences from control values were seen in the rate of turnover of NE or the concentrations of DA, AChE or MAO at 45 days. Exposure in utero to 6-6 rad produced no detectable postnatal effects on the brain neurochemical parameters measured.


Biological properties and response to x-rays of first-generation transplants of spontaneous mammary carcinomas in C3H mice. First-generation transplants of spontaneous mouse mammary carcinomas have been used extensively for radiobiological investigations of fractionated irradiation schedules, r.b.e. of fast neutrons and effectiveness of radiosensitizers, as reported elsewhere. The present work investigates the growth characteristics of the tumours; the criteria for the choice of end-points used in the definition of 'local control' of irradiated tumours; the reason for a decrease of 30 per cent in X-ray dose required to control tumours in females as compared with male mice; the proportion of hypoxic cells and its variation with time (reoxygenation) after a single dose of 1500 rad of X-rays; and the repair capacity of tumour cells within 24 hours after a substantial first dose of X-rays. Evidence is presented that the male-female difference was due to a higher proportion of hypoxic cells in tumours in male than in female mice. The repair of sub-lethal injury in tumour cells made hypoxic was slightly less than in skin made hypoxic but not significantly so. In the two-dose experiments on clamped tumours, no evidence of induced synchrony was found.


Partial purification and properties of cathepsin D in the retinal pigment epithelium. Cathespin D from the retinal pigment epithelium of bovine eyes was purified about 25-fold from a crude extract of retinal pigment epithelium by acid treatment, ammonium sulfate fractionation, and Sephadex G-200 column chromatography. The purified enzyme hydrolyzed bovine serum albumin optimally at pH values close to 4.0. Exposure of the enzyme to 60 degrees C. for 2 minutes resulted in 50 per cent inactivation of the activity. The enzyme activity was completely inhibited by 0.1 microgram per milliliter of pepstatin, slightly inhibited by trasylol, and not affected by soybean trypsin inhibitor. The apparent molecular weight of cathepsin D was estimated to be about 60,000 by gel filtration on Sephadex G-200.


Color vision: blue deficiencies in children? Recent publicized reports based on the use of the Farnsworth Panel D-15 test suggest that a large percentage of young children have a deficiency of blue vision (tritan type). In our study, 413 school children (ages 3 to 10) were tested with both the Farnsworth Panel D-15 test, as well as the A.O. H-R-R plates. None of the children failed either test for blue-yellow vision when traditional scoring instructions were observed. As in previous reports, we find that the children make a number of minor errors which adults rarely make. These errors show marked age-related patterns, being more frequent in younger children. However, further analysis of these errors revealed that the relative frequency with which particular error types were made on the D-15 test was significantly correlated with the existing perceived color difference data for the visually normal adult population. In addition, retesting significantly reduced all error types and reversing the test sequence demonstrated that most of the minor errors were made in the last half of the test regardless of the color vision task. The overall increase in the number of minor test errors seen with young children seems unrelated to color defects. The modified scoring methods in conjunction with the characteristics of the Panel D-15 test design account for the high percentage of errors classified as errors of blue vision.