Analysis of time intervals involved in admission to a coronary care unit.

Time intervals between the onset of the presenting symptom (chest pain) and arrival in a coronary care unit were studied for 221 admissions arranged by conventional means. The median figure for "patient delay" was 60 minutes, for "general-practitioner delay" 20 minutes, for "ambulance delay" 30 minutes, and for "transit delay" 30 minutes. The median "total delay" was three hours 30 minutes.Only 4.5 per cent of the patients were under intensive coronary care within one hour, the time of the highest mortality risk. A mobile coronary service should be capable of increasing the proportion of patients brought under special care within the first hour, but the time taken by the patient to realise the nature of the emergency and summon aid is likely to remain the most critical factor.


A general-practitioner ward in a new district general hospital.

So far there are relatively few general-practitioner wards in district general hospitals in the National Health Service. The work of one such general-practitioner ward at Queen Mary's Hospital, Sidcup, is described and the advantages of this system of care for patients and doctors discussed.


Attaching community psychiatric nurses to general practice.

A scheme for attachment of psychiatric nurses from hospital to group practice in Oxford is described. One community psychiatric nurse can work satisfactorily with eight general practitioners covering a population of about 18,000. From analysis of a working year, it is concluded that this arrangement improves the care of patients in the community by providing psychiatric help at times when it was previously unavailable or unacceptable.The implications of such a scheme for the workings of the primary health care team and the hospital psychiatric service are considered, and a case is made for a further study involving a comparison between practices with and without the attachment of a community psychiatric nurse.


Seeing two doctors at once in general practice.

We report the reactions of 250 patients who saw two doctors together, a general-practitioner trainer and a vocational trainee, when they came to a general practice for consultation.Over 80 per cent were neutral and the remainder were almost equally divided between those who preferred to see two doctors and those who preferred to see their own doctor alone.Selected favourable statements outnumbered adverse comments by about ten to one, although allowance must be made for the desire of patients to please their doctor.


Using the first consultation in acute illness for teaching third year medical students.

We have introduced clinical teaching in general practice for students in their first clinical year. The students are present at the patient's initial consultation for an acute illness and thus see a wide range of morbidity which is seldom found in hospital. Log books are used to record such factors as the patient's presenting complaint, the diagnosis that is made and the presence of significant social and psychological aspects of the physical condition. Although there were only four two-hour teaching sessions, the frequency and the range of presenting complaints seen by students approximates to that in general practice. The opinions of both the tutors and the students to this form of teaching have been favourable.


The university department of general practice: its function and role.

The need is stressed for university departments of general practice to examine their role and create a philosophy which will guide their function. The success of a department depends upon clear objectives, teamwork, and integration with the teaching given by other clinical departments in the medical school. The contribution of general practice to undergraduate training is discussed and problems associated with the recruitment of staff are indicated.


Screening the elderly in general practice.

All the 855 patients over the age of 65 in one general practice were reviewed. Those under care were excluded (316-37 per cent), and the rest were offered a screening examination in the practice. In all, 335 were examined and several had been previously screened. The yield of conditions found is reported and the advantage of the work in general practice discussed.


Two knots in the umbilical cord.

A case of two true knots occurring in an umbilical cord is reported because of its relative rarity. The literature is reviewed. The cause of this potentially dangerous phenomenon is discussed, and a recommendation for further study made.


An approach to general oncology: principles and procedures.

The obstetrician-gynecologist is frequently the only physician to attend women during their reproductive years. Malignant disease outside the pelvic organs is a fairly frequent occurence in this age group. Certain findings in the patient's history and physical examination can suggest malignant disease. The routine laboratory examination can also provide indications of the presence of a neoplastic process. Once this process is suspected, histologic proof of malignancy must be obtained before further staging and therapy are considered. The extent of the disease is important for the planning of therapy, i.e., whether it is to be surgery, radiotherapy, chemotherapy or some combination of the three. Adjuvant chemotherapy is recognized as a form of treatment designed to eradicate micrometastases, prevent the occurrence of subsequent clinical metastatic disease and, as a result, improve survival.


Malignant lymphoma: implications during the reproductive years and pregnancy.

The malignant lymphomas are reviewed, and involvement of urogenital-ridge derivatives, including the reproductive organs, is summarized. Implications of therapy for pelvic lymphoma are discussed. It is shown by a retrospective analysis that Hodgkin's disease has little effect on fertility, the course of gestation, delivery or fetal wastage and that maternal death is not increased. No adverse effect of pregnancy on the symptoms or longevity of women with Hodgkin's disease can be demonstrated. Women diagnosed in pregnancy as having lymphoma should undergo therapeutic abortion so that proper staging and therapy may be given. Pregnancies over 32 to 34 weeks should be induced. Women previously treated for lymphoma may become infertile as a result of therapy. Those not infertile after therapy should avoid pregnancies since there is a potential risk of malformations and malignancies in the offspring.


Thyroid cancer: relationship to radiation exposure and to pregnancy.

Exposure to radiation results in an increased occurrence of nodularity to the thyroid and, more important, the development of cancer in a significant proportion of patients. Near-total thyroidectomy is recommended in those patients with a history of irradiation who are found on physical examination of the thyroid to have one or more nodules. Although pregnancy appears to have no effect on the course of thyroid carcinoma and the tumor has no effect on pregnancy, because of the numerous stimuli to thyroid growth during pregnancy, we feel that pregnancy is best avoided by women with known residual disease.


Acute leukemia during reproductive life: its course, complications and sequelae for fertility.

Acute leukemia is less common during the reproductive years than in children or in post-menopausal women. Effective chemotherapy exists for adult lymphocytic leukemia, and the median survival is 18 to 20 months. Acute myelogenous leukemia still has a less favorable prognosis, with a medial survival of 12 months despite effective chemotherapeutic agents. The occurrence of acute leukemia in pregnancy does not change the overall prognosis, which depends primarily on the cytopathologic types. If leukemia occurs during the first trimester, therapeutic abortion is advised since the rate of spontaneous abortion after chemotherapy is high in the first trimester and fetal malformations are common. Acute leukemia can be treated in the second and third trimesters with little effect on the pregnancy or fetus. In patients cured of acute leukemia, the potential for subsequent pregnancies exists with little likelihood of increases in fetal malformations.


Consequences of radiotherapy and antineoplastic therapy for the fetus.

The consequences of radiation and antineoplastic therapy on the fetus are summarized. Animal and atom bomb studies clearly demonstrate the carcinogenic effects of radiation. Less information is available on neoplasia and neonatal malformations induced by chemotherapy, but there may be an increased risk. The delayed consequences of radiation and chemotherapy are not well known and require further study.


Dermatomyositis following rhabdomyolysis.

A case is presented, in which classic dermatomyositis occurred six weeks after documented rhabdomyolysis. The literature concerning the immunopathogenesis of dermatomyositis is briefly reviewed.


Polymyositis in a patient with multiple neoplasms.

A 64 year old woman with a past history of panhysterectomy and oophorectomy for carcinoma of the body of the uterus (1950) and partial colectomy for carcinoma of the colon (1971), presented in 1972 with severe weakness of the proximal girdle muscles and histological evidence of polymyositis. A detailed search disclosed no tumor and she was treated with prednisone. Two years later, investigations for iron deficiency anemia revealed two polyps in the colon. Pathological examination of the resected colon disclosed two separate foci of adenocarcinoma and a number of adenomatous polyps. Three months later, further investigations for melena led to the discovery of a gastric carcinoma. Due to the extent of the tumor, she was subjected to gastrectomy. splenectomy, and excision of the tail of the pancreas, but died of postoperative complications. At autopsy, no residual cancer was detected, but a meningioma was found. The association of polymyositis with malignant tumors has been recognized for a long time, but only two previously reported patients have had more than one cancer. Although a causal relationship is difficult to establish, continued vigilance for neoplasms is advocated during the follow-up period.


Classical rheumatoid arthritis in a patient with Reiter's syndrome.

A 44 year old white male presented with sterile urethritis, anterior uveitis, painless oral ulcers, low back pain, and synovitis of the knees and left ankle. Unilateral sacroiliitis and limited spondylitis further supported a diagnosis of Reiter's syndrome. Serum rheumatoid factor was present. The patient subsequently developed morning stiffness, symmetrical polyarthritis of the hands and wrists, and an olecranon subcutaneous nodule. Histology of the nodule and synovium was consistent with rheumatoid arthritis. Histocompatibility antigen typing established the presence of HLA B27. The occurrence of rheumatoid arthritis and Reiter's syndrome in the same patient is quite rare, and the infrequent co-existence of these two inflammatory rheumatic diseases is discussed.


Rheumatoid pericarditis: comparison of immunologic characteristics of pericardial fluid, synovial fluid, and serum.

A comparison was made of the immunological characteristics of serum, synovial and pericardial fluids obtained from a 54 year old man with classic rheumatoid arthritis and pericarditis. The synovial and pericardial fluids had low complement levels and immune complexes were detected using both biological and physical methods. The serum had normal complement levels and no immune complexes could be demonstrated. The presence of immune complexes and complement depletion in the synovial and pericardial fluids supports the concept of local production of immune complexes, and is in keeping with a Type III mechanism of immunologic injury.


Acute leukemia in rheumatoid arthritis treated with cytotoxic agents.

Acute leukemia is described in two patients treated with cytotoxic agents for a destructive, seropositive rheumatoid arthritis. Both patients had received longterm azathioprine therapy. In addition, one patient had been treated with cyclophosphamide, the other with melphalan. Chromosomal abnormalities were noted in both patients. Studies in one patient included colony forming units, ferrokinetics, electron microscopy of bone marrow, and autopsy examination. All reports of acute leukemia associated with cytostatic drugs in the literature to date are reviewed and the possible mechanisms discussed. It is suggested that patients with rheumatoid arthritis treated with azathioprine and alkylating agents may have an increased risk of developing a therapy-related acute leukemia.


Pharmacokinetic and clinical studies of a new uricosuric agent - benzbromarone.

Benzbromarone, a potent uricosuric agent, is a benzofuran derivative with a bromine on the 3rd and 5th positions of the benzene ring. Readily absorbed after oral administration, it is promptly dehalogenated in the liver and excreted via the biliary system. Peak drug concentration usually precedes maximal uricosuria following a single dose of 40 mg of benzbromarone, since benzarone, one of the two metabolites, likewise has a uricosuric action. Longterm studies in 24 gouty patients indicate that the drug is well tolerated. It has not produced any skin rash or renal colic. Renal hemodynamics, blood picture, and liver enzymes were unchanged. Since it is eliminated by the biliary tract, it may cause diarrhoea in some patients. Being a very potent uricosuric agent, it is not advocated in patients with a history of uric acid lithiasis. The uricosuric effect is not liable to be counteracted when used in conjunction with hyperuricemic diuretics. The drug is particularly useful in patients with chronic gouty arthritis and tophi, either refractory or allergic to probenecid, sulfinpyrazone, or allopurinol.


Postoperative heterotopic ossification in patients with ankylosing hyperostosis on the spine (Forestier's disease).

Heterotopic ossification following hip surgery occurred in three patients with ankylosing hyperostosis of the spine. No technical difficulty during surgery was encountered in these individuals. The occurrence of this postoperative complication, coupled with the appearance of bony outgrowths at sites of ligament attachment throughout the axial and extra-axial skeleton in patients with ankylosing hyperostosis of the spine, suggests the presence of an underlying ossifying diathesis, diffuse idiopathic skeletal hyperostosis (DISH). A significant number of patients with DISH possess the second segregant series antigen, HLA-B27, a feature they share with individuals with other arthropathies characterized by abundant ossification; this gene may be closely related to one which influences bone formation. The possible association of postoperative heterotopic ossification and ankylosing hyperostosis of the spine indicates that a radiographic examination of the vertebral column in patients undergoing hip surgery may be a useful screening procedure.


Radiologic and scintiscan findings in HLA-B27 negative patients with ankylosing spondylitis.

Of 189 consecutive patients seen with definite ankylosing spondylitis, 17 did not possess the transplantation antigen HLA-B27. These 17 patients had less severe radiological evidence of disease than the group as a whole, or a sub-group matched for age, sex, and duration of disease. This supports the suggestion that the HLS-B27 antigen itself may play a role in the pathogenesis of the disease, and does not serve merely as a marker for a linked immune response gene.


Stereochemical studies on medicinal agents. 20. Absolute configuration and analgetic potency alpha-promedol enantiomers. The role of the C-4 chiral center in conferring stereoselectivity in axial- and equatorial-phenyl prodine congeners.

Opical antipodes of the axial phenyl analgetic, alpha-promedol hydrochloride (3), were prepared and the absolute stereochemistry wasd determined by relating one of the enantiomers to its gamme diastereomer having the 2S, 4S,5R configuration. The analegetic potency of (+)-(2R,4S,5S)-3 is 20 times that of morphine, while its enantiomer, (-)-(2S,4R,5R)-3, is inactive at 50 mg/kg. These results are in accord with prior reports which indicate that substitution of a 3-or 5-alkyl group on the pro-4S enantiotopic edge of the piperidine ring leads to enantiomers which have greater potency than those substituted in an identical position on the pro-4R edge. This coupled with the fact that the torsion angle between the axial phenyl group and piperidine ring in (+)-3 is of the same sign as its equatorial congeners, suggests that the C(3)-C(4)-C(5) moiety and its substituents at C(4) are located in a similar chiral environment on the receptor. In contrast, the C(2)-N-C(6) portion of the axial and equatorial molecules does not bind in the same receptor environment, and it is suggested that different modes of interaction in the prodine series arise from different orientations of this moiety.


Irreversible enzyme inhibitors. Inhibitors of guinea pig complement derived by quaternization of substituted pyridines with benzyl halides.

A series of 83 compounds derived from hydrocarbon-substituted pyridines by quaternization with PhCH2Br usually containing a 2-SO2F or 6-Cl-2-SO2F group was synthesized and evaluated as inhibitors of guinea pig complement and in most cases its C1 component. The most active compounds were 3-(4-phenylphenylbutyl)-N-(6-choro-2-fluorosulfonylbenzyl) pyridinium bromide (43) and 3-(4-phenylphenylbutyl)-N-(2-fluorosulfonylbenzyl) pyridinium bromide (44), each showing 50% inhibition at 7.8 muM. The most effective irreversible inhibitor of the C1 component was N-(6-chloro-2-fluorosulfonylbenzyl)-5,6-benzoquinolinium bromide (87), which showed 50% inhibition at 4 muM.


Potential inhibitors of S-adenosylmethionine-dependent methyltransferases. 4. Further modifications of the amino and base portions of S-adenosyl-L-homocysteine.

Structural analogues of S-adenosyl-L-homocysteine (L-SAH), with modifications in the amino acid or base portions of the molecule, have been synthesized and evaluated for their abilities to inhibit the transmethylations catalyzed by catechol O-methyltransferase (COMT), phenylethanolamine N-methyltransferase (PNMT), histamine N-methyltransferase (HMT), hydroxyindole O-methyltransferase (HIOMT), and indoleethylamine N-methyltransferase (INMT). From these studies some interesting and potentially useful differences in the structural features of L-SAH needed to produce maximal binding to these methyltransferases were detected. This paper provides evidence that 8-azaadenosyl-L-homocysteine is a potent and selective inhibitor of HIOMT, whereas N6-methyladenosyl-L-homocysteine and N6-methyl-3-deazaadenosyl-L-homocysteine are selective inhibitors in INMT. In contrast, it was found that S-tubercidinyl-L-homocysteine was a fairly potent, but nonselective inhibitor of all of the methyltransferases studied. The differences and the similarities in the requirements for the binding of SAH to methyltransferases which were detected in this study and earlier studies from our laboratory, are described. The possibilites of utilizing differences in binding requirements for the design of SAH analogues as specific inhibitors of methyltransferases are discussed.


Potential inhibitors of S-adenosylmethionine-dependent methyltransferases. 5. Role of the asymmetric sulfonium pole in the enzymatic binding of S-adenosyl-L-methionine.

The configuration at the asymmetric sulfonium pole of S-adenosyl-L-methionine (SAM) necessary for optimal enzymatic binding and methyl donation has been elucidated in this study. For the transmethylations catalyzed by catechol O-methyltransferase, phenylethanolamine N-methyltransferase, histamine N-methyltransferase, and hydroxyindole O-methyltransferase, it was demonstrated that only the natural (-) enantiomer of SAM was active as a methyl donor. The corresponding (+)-SAM, which was prepared by enzymatic resolution of synthetic (+/-)-SAM, was shown to be inactive as a methyl donor in these enzymatic reactions. The (+)-SAM was found, however, to be a potent inhibitor of each of these enzyme-catalyzed transmethylations. These results suggest that the (+) enantiomer offers a nonproductive configuration for the methyl-transfer reaction itself; however, this configuration fails to hamper enzymatic binding. These results are discussed relative to the geometric requirements necessary for the methyl-transfer reaction and the requirements for enzymatic binding.


Potential inhibitors of S-adenosylmethionine-dependent methyltransferases. 6. Structural modifications of S-adenosylmethionine.

Structural analogues of S-adenosyl-L-methionine (SAM), with modifications in the amino acid, sugar, or base portions of the molecule, have been synthesized and evaluated as either inhibitors and/or substrates for the enzymes catechol O-methyltransferase, phenylethanolamine N-methyltransferase, histamine N-methyltransferase, and hydroxyindole O-methyltransferase. To evaluate these analogues as substrates for SAM-dependent methyltransferases, the corresponding methyl-14C compounds were prepared and tested for their abilities to donate their methyl group to the appropriate acceptor molecules. In addition, the unlabeled SAM analogues were tested for their inhibitory activities in these same transmethylation reactions. In general, it could be conlcuded from these studies that methyltransferases show very strict specificity for the structural features of SAM. This strict specificity holds for the enzymatic binding and methyl-donating abilities of this molecule. In fact, it could be concluded from the results of this study that methyltransferases show a higher specificity for the structural features of the substrate L-SAM than for the structural features of the product S-adenosyl-L-homocysteine (L-SAH).


Potential antitumor agents. 19. Multiply substituted 4'-(9-acridinylamino)methanesulfonanilides.

A series of 42 multiply substituted 4'-(9-acridinylamino)methanesulfonanilides has been prepared and evaluated in the L1210 system. In addition to biologic activity changes resulting from altered agent lipophilic-hydrophilic balance variants containing both acridine 4-CH3 and 3-NH2, NHCOCH3 or NO2 substituents have reduced activity. Variants 3,6-disubstituted, using functions of differing electronic character, have depressed activity, suggesting that there is limited site bulk tolerance. Asymmetric 3,5-disubstitution should then be the preferred pattern; the 3-ND-5CH-3'-OCH variant is the most dose potent (optimum dose qd 1-5, 1.25 mg/kg/day) of the high activity agents of this series so far prepared.


Structural requirements for biological activity among antileukemic glaucarubolone ester quassinoids.

A C-15 ester substituent is required for significant antileukemic activity among the glaucarubolone ester quassinoids, and variations in the ester group are not accompanied by particularly marked changes in antileukemic activity. Unsaturation at the 3,4 position is advantageous for optimal activity, and hydrogenation of this double bond results in marked diminution in both cytotoxicity toward KB cells in tissue culture and inhibitory activity against the P-388 lymphocytic leukemia in mice.


Synthesis and antimyoctic properties of 1-(2-alkyl-2-phenylethyl)-1H-imidazoles.

The synthesis of 1-(2-alkyl-2-phenylethyl)-1H-imidazoles was accomplished starting from the corresponding phenylacetonitriles. Via alkylation, esterification, and sodium borohydride reduction-in the presence of lithium iodide-beta-phenylalconols were obtained. Mesylation of these alcohols and refluxing with imidazole in dimethylformamide furnished title compounds, which were active in vitro against dermatophytes, yeasts, other fungi, and gram-positive bacteria and in vivo as well as in vitro against Candida albicans.


9-Nor-9-hydroxyhexahydrocannabinols. Synthesis, Some behavioral and analgesic properties, and comparison with the tetrahydrocannabinols.

The racemic mixture and levo isomer of both 9-nor-9alpha-hydroxyhexahydrocannabinol and its 9beta-hydroxy isomer were prepared. Both alpha-and beta-hydroxy compounds were active in the dog ataxia test and depressed spontaneous activity in mice. However, only the beta-hydroxy compound was an analgesic in mice morphine-like potency. The behavioral and analgesic properties of these compounds may be mediated through different sites or mechanisms and may, therefore, be separable.


Study of U.S. medical school applicants, 1974-75.

The applicant activity for the 1974-75 first-year class in U.S. medical schools presents an unusual combination of statistics. There were more applicants than ever before, but the annual growth rate showed a decline, a trend that began in 1973-74; the national acceptance average remained unchanged; and the average application frequency per individual was accelerated. Most of the traditional tables cover five years of historical data (1970-71 through 1974-75), while the new features--acceptance success for first-time and repeat applicants and ability levels by acceptance success and application frequency--depict data for one year (1974-75). As in past studies, the conclusion enumerates major efforts instituted by the Association of American Medical Colleges to assist medical schools with admission problems. The most important innovations among these were two new task forces--one for minority admissions and one for financial aid.


The future of pathology: a Delphi study by pathology department chairmen.

This paper reports the results of a study by and of chairmen of pathology departments in American and Canadian medical schools directed toward discovering chairmen's perceptions and attitudes about the future of pathology. Over 100 of a total of 143 chairmen participated in some or all phases of this study in which the Delphi approach was used. Sixty-five chairmen completed all four rounds of questionnaires. Most chairmen are deeply concerned about increasing federal regulation of medicine. They expect to play a greater role in all phases of medical education with more emphasis on the basic science aspects of pathology. They also foresee a desirable shifting of residency training programs away from small hospitals to the larger medical centers. This shift will result in fewer but longer training programs.


A standardized interviewing technique for evaluating postgraduate training applicants.

In an effort to streamline the personal interview and to reduce the influence of subjectivity inpreparation of ranking lists for postgraduate year-one applicants, a standardized interview was constructed for use in evaluating condidates for admission to a training program in internal medicine. The interview was conducted in a uniformly structured manner by 14 interviewers of 260 applicants. Each applicant received an interview score which correlated well with the final decision of the Intern Selection Committee. For each interviewer various measures of performance were obtained which allowed a classification into "hard" versus "easy" interviewer and indicated the comparability of each interview's evaluations with the final decisions. Thus, the standardized interview resulted in quantifiable data in the form of uniform evaluations of applicants and interviewers.


A study of student attitudes toward a psychiatric clerkship.

Sixty-seven third-year medical students at the University of Ottawa were interviewed at the beginning and end of a month-long clerkship in psychiatry. Two attitude categories were designated: "attitude-positive" (AP) differentiated subjects with positive clerkship expectations or attitudes for "attitude-negative" (AN) subjects who had negative expectations or attitudes. Differences between preclerkship APs and ANs are described. Postclerkship interviews revealed a general improvement in attitudes toward psychiatry and the psychiatric clerkship. Statistically significant differences were noted between postclerkship APs and ANs in the following: attitudes toward psychiatry, attainment of preclerkship objectives, reduction of anxiety levels, and nature of supervisory experiences. Postclerkship attitudes may be predicted to some extent prior to the clerkship. The potential for a negative postclerkship attitude may be modified by positive clerkship experiences. The importance of identifying students vulnerable to the stresses of psychiatric clerkship is emphasized.


Pediatric-psychiatric liaison as a model for teaching pediatric residents.

The pediatrician's function as a comprehensive family health practitioner has frequently been ignored. A major problem is that pediatric residents are not trained or are inadequately trained to assess emotional, behavioral, and family problems that may be an integral part of the patient's symptoms. At the Children's Hospital of Philadelphia, a pediatric-psychiatric liaison program has evolved in which pediatric residents learn the principles and skills necessary to manage these problems. Ultimately, the liaison program will enable the staff pediatricians who use these principles to assume appropriate responsibility for educating the pediatric trainees.


Electrolyte transport by gallbladders of rabbit and guinea pig: effect of amphotericin B and evidence of rheogenic Na transport.

Ion transport and electrical properties of rabbit and guinea pig gallbladders were investigated to gain further information about the active transport mechanism that mediates fluid absorption. The intracellular and transepithelial electrical potentials were measured simultaneously using the microelectrode technique. Exposure of the mucosal surface to Amphotericin B resulted in the prompt development of a serosa-positive electrical potential difference (PD) which could not be attributed to an alteration in ion diffusion potentials across either the cell membrane or across the tight junction. Because the Amphotericin B-induced PD was immediately dependent on warm temperatures and O2, and was independent of NA and K concentration gradients across the cell membrane, it is suggested that active ion transport is directly responsible for the PD. Since the PD was abolished in the absence of Na in the bathing solutions, a rheogenic Na pump is postulated; this pump also appears to be operative in tissues not exposed to Amphotericin B. The specific tissue properties altered by Amphotericin B to produce a serosa-positive PD remain incompletely defined. The results of the present study indicate that ion transport by rabbit gallbladder in vitro is a consequence of a rheogenic active Na transport mechanism at the basolateral membranes which, in conjunction with a coupled NaC1 influx process at the mucosal border, ultimately results in absorption of NaC1 and water.


A study of the relationship between inhibition of anion exchange and binding to the red blood cell membrane of 4,4'-diisothiocyano stilbene-2,2'-disulfonic acid (DIDS) and its dihydro derivative (H2DIDS).

DIDS (4,4'-diisothiocyano stilbene-2,2'-disulfonic acid) and H2DIDS (4,4'-diisothiocyano-1,2-diphenyl ethane-2,2'-disulfonic acid) binding to the human red cell membrane proteins were studied as a function of concentration, temperature and time. Most binding sites were common to both. The common sites were in band 3 of SDS polyacrylamide gel electropherograms (Steck, 1974. J. Cell Biol. 62:1), an unidentified adjacent band, and glycophorin. Reversible and irreversible binding occurred; both inhibited sulfate equilibrium exchange. The time courses of irreversible binding to band 3 and total binding to the membrane as a whole were biphasic. About 20% of H2DIDS and greater 60% of DIDS binding were rapid, independent of temperature. Slow H2-DIDS binding was monoexponential, activation enthalpy 23 kcal/mole. The stoichiometry of irreversible H2DIDS binding to band 3 was 1.1-1.2, concentration-dependent. Under the conditions studied (0-50 muM, hematocrit 10%, 5-37 degrees C) binding to band 3 was a constant fraction of total binding, 0.7 for H2DIDS and 0.8 for DIDS. Inhibition was a linear function of total binding, binding to band 3, and therefore also to nonband 3 sites, with either inhibitor during both phases, H2DIDS inhibition was complete at 1.9 X 10(6) or 1.2 X 10(6) molecules/cell total and band 3 binding respectively. For DIDS the corresponding figures were 1.3 X 10(6) and 1.1 X 10(6). It is shown how reagents of mixed function can react with biphasic kinetics. Binding to multiple contiguous sites may exhibit concentration-dependent stoichiometry. Under such conditions a linear inhibition-binding relationship is neither a necessary nor a sufficient condition for the identification of transport sites.


On the question of an electrokinetic requirement for phospholipase C action.

The phospholipase C of clostridium welchii (alpha toxin) has an absolute requirement for trace quantities of Ca2+. It attacks pure phosphatidylcholine particles (smectic mesophases) having a close-packed bilayer structure only when their surface zeta potential is made positive by the addition of certain divalent ions (e.g., Ca2+) to the aqueous phase or by the presence of low concentrations of long chain cations to the lipid. Alternatively, if the rotational freedom of individual phospholipid molecules is increased by the insertion of short n-alkanols (e.g., hexanol) into the bilayer or when a monolayer of the substrate at an air/water interface is expended, enzymic hydrolysis can occur without any requirement for a net postive charge on the surface.


"Metabolic" action potentials in Acetabularia.

The transient depolarizations in Acetabularia which fulfill the essential criteria of an action potential (all-or-none characteristics, triggering by depolarization, propagation, etc.) are investigated. These action potentials are analyzed by conductance measurements and voltage clamp experiments on the basis of the analog circuit of the membrane (Gradmann, D. 1975, J. Membrane Biol. 25:183). It is concluded that these action potentials do not arise by permeability changes of the passive diffusion channels, but by the active pathway of the electrogenic pump, which consists of a voltage source EP of about --20 mV in series with two nonlinear conducting elements P1 and P2, the latter and EP being shunted by a large quasi capacity CP of some mF cm-2. The nonlinear current-voltage relationship of the carrier system (P1) is not changed during the action potential but has an effect on its time course. However, the elements P2 and CP, which probably reflect metabolic entities, are suggested to control the action potentials.


Electrical properties of Valonia ventricosa.

The cytoplasmic electrical potential and membrane resistance of mature cells of Valonia ventricosa have been measured by inserting a microelectrode concentric with another electrode into the vacuole of the cell. The cytoplasmic region was investigated by advancing the microelectrode into the cell wall from the vascuolar side. The results revealed a unique region where the vascuolar electric potential and membrane resistance changed in a simultaneous single step to values close to zero. The measured potential always remained positive immediately after the step. At no time was a highly negative potential region encountered. Further penetration of the microelectrode revealed a low resistance negative potential region of --12.6 +/- 1.1 mV associated with the cell wall. Experiments were also carried out on aplanospores of V. ventricosa to compare mature and immature cells. The chemical composition of the vacuolar and protoplasmic phases of mature cells was determined. The results agreed with previous results except that the C1- ion content of the protoplasm was significantly higher at 381 +/- 20 mmoles/liter (H2O). It was concluded that mature cells of Valonia are significantly different from immature cells in that no highly negative potential cytoplasmic region was found in mature cells. It was considered that the measured step change in electric potential and membrane resistance occurred at the plasmalemma and that the tonoplast was a region of very low resistance. The implications of these findings in terms of models of ion transport into Valonia are discussed.


Early chick neuroretinal responses following direct exposure to methotrexate.

Explants of 4.5-day-old chick embryonic neuroretinas with mesenchyme were exposed to Methotrexate (MTX) in medium 199 with embryo extract. Proliferative responses of the cultured neuroretinas were followed radioautographically by administration of 3H-thymidine to the cultures. The DNA synthetic, mitotic and pyknotic responses of the ventricular cells of the neuroretina were followed over a 16-hour period. The responses observed suggested that MTX caused a synchronization of the ventricular cells in the pre-mitotic phases with no direct inhibition of mitosis. Furthermore, prolonged exposure to MTX resulted in the accumulation of labeled pyknotic cells, indicating a decline in the regenerative capacity of the proliferative ventricular cells.


A stereological analysis of the ultrastructure of the lungs of wild mice living at low and high altitude.

Stereological analysis of the ultrastructural composition of the pulmonary alveolo-capillary region of mice living at sea level compared with that of the same species (Phyllotis darwini) genetically adapted to life at 4,660 m reveals a trend at high altitude towards a greater volume percentage of tissue components. On a weight-specific basis, non-circulating tissue occupies a significantly greater volume in high-altitude mice, but air space and capillary contents are not correspondingly greater. Since the arithmetic mean thickness of the tissue layers and of the air-blood barrier are the same in the two altitudinal groups, the average alveolus must have a smaller volume in the high-altitude mice. Epithelial, endothelial, and erythrocyte surface areas per gram body weight are significantly greater in the high-altitude mice. Nuclear counts indicate that the larger lungs of mice adapted to high altitude are due to larger Pneumocyte I and II and endothelial cells rather than to an increase in the number of these cells. Hematocrits measured within the pulmonary capillaries in the two altitudinal groups were equal. An heretofore unrecognized feature of possible adaptive value is the surface/volume ratio of erythrocytes, which is similar for erythrocytes in alveolar space of mice at low and high altitudes but within lung capillaries is 14.7% greater at high altitude.


Formation of nucleoside 5'-polyphosphates under potentially prebiological conditions.

Aqueous solutions of linear inorganic polyphosphates incubated in presence of Mg ions depolymerize to give trimetaphosphate. The presence of a nucleoside 5'-phosphate has little influence upon the reaction. Drying the products obtained by incubating a linear polyphosphate with Mg ions in the presence of a nucleoside 5'-phosphate yields nucleoside 5'-polyphosphates. The prebiological relevance of the reactions is discussed.


Penguin evolution: protein comparisons demonstrate phylogenetic relationship to flying aquatic birds.

Quantitative immunological comparisons of three avian proteins, transferrin, ovalbumin, and penalbumin, indicate that penguins are phylogenetically most closely related to loons, albatrosses, herons, and grebes. These data support the theory that the ancestors of penguins were flying oceanic birds and that flightlessness in penguins has evolved independently from flightlessness in ratites.


Human skeletal muscle proteins. The primary structure of troponin C.

The primary structure of the major component of human skeletal muscle troponin C has been established. The troponin C was purified by ammonium sulphate and isoelectric fractionation, followed by two chromatographic steps on DEAE Sephadex. The sequence was determined from the different overlapping enzymic peptides and by dansyl-Edman degradation. The only difference between rabbit skeletal muscle troponin C and the major component of human skeletal troponin C was found at position 112: Ala (rabbit), Pro (human). The partial amino acid sequence of the first 86 residues of the minor component of human skeletal troponin C was found to resemble the troponin C from bovine cardiac muscle. The only difference between them, has tentatively been located at position 62: Glu (human), Asp (bovine). These similarities suggest that troponin C is, from the point of view of molecular, one of the most conservative proteins so far studied.


Evolution of flightless land birds on southern continents: transferrin comparison shows monophyletic origin of ratites.

A biochemical approach was used to study the evolution of ratite birds, i.e., the ostriches, rheas, cassowaries, emus, and kiwis. Quantitative immunological comparison of transferrin from ratites, tinamous, and other flying birds indicates that all the ratites and tinamous are allied phylogenetically and that they are of monophyletic origin relative to other birds. To explain the current geographic distribution of ratites and the magnitude of the transferrin distances, it is supposed that the ancestors of these flightless birds walked across land bridges between the southern continents during Cretaceous times.


A preliminary classification of human functional sexual disorders.

A preliminary classification is presented for functional human sexual disorders. This system is based on objective behavior and reports of distress. Five categories of sexual disorders are proposed, including the behavioral, psychological and informational components of sexual functioning in the individual and the couple.


Primary orgasmic dysfunction: essential treatment components.

In an attempt to determine the essential components of a successful treatment regime for primary orgasmic dysfunction, the principle treatment approaches are reviewed to elucidate the similarities in different programs which have reported similar outcome data. It is concluded that the systematic desensitization studies, the masturbatory training approaches, and the Reproductive Biology Research Foundation series are all effective treatment procedures. It appears that all three approaches employ graduated exposure to sexual stimuli plus some form of directive psychotherapy emphasizing interpersonal skills acquisition. These may be the essential treatment components.


A short-term, intensive workshop approach for the treatment of human sexual inadequacy.

A rapid treatment approach to common sexual dysfunctions has been used in treating 59 couples, including 74 symptomatic individuals. Using a multidisciplinary team approach in an intensive 2 1/2 day workshop format, symptom improvement has been obtained in 86.5% of the dysfunctional individuals, with complete symptom reversal in 63.5%. The intensive workshop format has resulted in a saving of both patient and professional time and is seen as a viable and successful alternative to more time-consuming approaches of treating various sexual dysfunctions.


Perceptual accuracy as a variable in marital adjustment.

This study investigated the ability of maritally-adjusted couples, couples attaining a divorce, and couples in counseling to predict the rewarding effects of their behavior on their spouse. Twenty-six couples, five obtaining a divorce, nine in counseling, and twelve adjusted couples completed a Marital Interaction Questionnaire in which they rated how rewarding each of the behaviors depicted was to them. Then each member predicted how rewarding it was to their spouse. Behaviors depicting six areas of marital interaction were included in the questionnaire. The computed perceptual accuracy scores were analyzed by a three-way classification-Analysis of Variance (ANOVA)-for unequal n's. This analysis yielded a significant main effect of marital status and a significant interaction between marital status by sex of spouse and between marital status by area of interaction. The maritally-adjusted group was always more accurate than the other two groups in their predictions, however, they were significantly more accurate only for selected areas of interaction.


In every marriage there are two marriages.

While investigators often have commented about discrepancies in the way a husband and a wife view the same marriage, little attention has been devoted to the implications such discrepancies have for marital and family therapy. As part of a continuing study of the differences between couples who seek marital therapy and those who seek sexual dysfunction therapy, this report examines these two clinical populations on the dimension of discrepant views of the marriage. Our results suggest that overall discrepancy scores may be an important indicator of stress between partners. In particular areas, however, such as rating the quality of the marriage, specific complaints about the marriage, and concerns about male sexual difficulties, marital therapy patients obtained significantly higher discrepancy scores than sexual therapy patients.


Gender and sexual experience as determinants in a sexual behavior hierarchy.

The present study sought to assess the influence of gender and previous sexual experience regarding the structure of the basic sexual behavior hierarchy. Results indicated that both gender and previous experience have significant effects. Overall, gender appeared to have a less substantial effect than previous experience, being more noteworthy for the similarities manifest between males and females than the few differences observed. Previous experience displayed a substantial effect, particularly in the upper portion of the hierarchy, with like-experienced groups showing marked similarity in their hierarchy patterns. Several significant gender-experience interactions were found regarding oral-genital behaviors, and a general trend was observed for females indicating negative appreciation from pre to postexperience. Males revealed positive appreciation from pre to postexperience on all but the most basic sexual behaviors. Conclusions were to the effect that while both variables influenced the hierarchy, effects were complex, and often mediated by additional factors.


Complement-fixing antigen of human sarcomas.

Further investigation of the humoral immune responses of patients with sarcoma to their tumors revealed a sarcoma-associated antigen that was readily detected by complement fixation. Circulating levels of antibody to this antigen, tentatively labeled S3, rose markedly after surgical removal of the tumor. Antibody to S3, as to S1 and S2, was highly prevalent in patients with various malignant tumors other than sarcoma.


Epidemiology of renal cell carcinoma in Connecticut, 1935-1973.

Data on over 3,700 patients with renal cell carcinoma, reported to the Connecticut Tumor Registry from 1935 through 1973, were used to assess incidence, survival, and associations of risk with demographic characteristics. Incidence increased over time among men, but not among women; a birth cohort effect suggesting increasing incidence rate over time was demonstrated for men. A comparison of male and female age-specific incidence rates indicated that, in the 15- to 39-year-old age group, men were three times more likely than women to develop the disease; after age 40, renal cell carcinoma was diagnosed in men twice as often as in women. Survival probability has increased from 1940 to the present time. A high density of persons per square mile was associated with a higher-than-expected incidence. No trends in incidence according to socioeconomic status were observed.


Changes with age in the hematopoietic system in a cesarean-derived, barrier-maintained colony of Wistar rats.

In a colony of cesarean-derived barrier-maintained inbred W rats given saline injections into the right pleural cavities, histologic and cytologic changes due to age were examined in the bone marrow, lymphatic tissue, and lungs; hematologic trends were also evaluated. The thymus showed two changes with age: 1) atrophy, which was evidenced by plasma cells near the blood vessels and among the cords of epithelial cells; and 2) disruption of the normal architecture of the gland. In all available thymuses, changes showed a transition toward malignancy. As the bone marrow showed increasing cellularity with time, polymorphonuclear cells and precursors appeared to increase. In lymph nodes, lymphocytes in the paracortical area were excessive and resembled the lymphocytes of the "lymphoid bursts" found in the thymus. In the lungs, small parabronchial and paravascular collections of mononuclear cells, occurring with slightly increasing frequency with age, were consistently found; however, any lung disease associated with these cells was not evident. In the blood, absolute numbers of mononuclear and polymorphonuclear cells were altered.


Hormone-dependent mammary tumors in strain GR/A mice. II. Preneoplastic and neoplastic properties.

In a series of transplant experiments, we investigated interactions between normal, ductal phase, and tumorous phase mammary tissues in GR/A mice, with particular respect to growth regulation. Transplants from hormone-dependent mammary tumors (HDT) transplanted into mammary fat pads already containing normal mammary ducts usually could not be located subsequently or, at best, displayed minimal growth. Growth regulation was also normal when two HDT transplants, placed in a single gland-free fat pad in nonpregnant hosts, produced ductal outgrowths displaying mutual avoidance behavior in which ducts did not touch and were normally spaced. A normal and HDT transplant in a single gland-free fat pad also showed identical, normal regulatory behavior. In contrast, HDT transplants in pregnant hosts or in hosts receiving exogenous hormone therapy displayed altered growth patterns in which neighboring tumors touched and eventually fused. When surrounded by normal tissues, the HDT continued to proliferate and often appeared to overgrow and engulf normal elements. We concluded that HDT tissues grown in nonpregnant hosts fully responded to those short-range regulatory influences characteristic of normal morphogenesis. When exposed to hormones of pregnancy, however, these interactions changed, and HDT tissues exhibited many characteristics of ductal carcinomas.


Hormone-dependent mammary tumors in strain GR/A mice. III. Effectiveness of supplementary hormone treatments in inducing tumorous phase growth.

Attempts were made to initiate hormone-dependent tumor (HDT) transformation in ductal phase mammary outgrowths. These outgrowths, when carried in virgin GR/A mice, were not tumorous and usually resembled the host's mammary glands. After 2-3 months' initial growth, the following hormone treatments were initiated: 1) An isologous pituitary was implanted into each fat pad having previously received an HDT transplant. Some neoplastic transformation of the pregnancy-dependent tumor outgrowth occurred after 1-2 months; all 10 mammary glands were well stimulated and had many hyperplastic alveolar nodules. 2) In experiments involving exogenous hormone administration, estrogen or progesterone administered alone caused no neoplastic changes in the 2- to 3-month-old ductal phase outgrowths. However, 1 mg progesterone plus 1 mug estrogen daily given sc for 3 weeks to both ovariectomized and intact mice with HDT transplants caused neoplastic changes in the outgrowths and induced small ductal hyperplasias in the host glands. Termination of hormone treatment resulted in a return to the normal ductal structure. The addition of 100 mug prolactin and 100 mug growth hormone to the progesterone and estrogen mixture did not further alter transplants but increased stimulation to the host glands.


A proper sequence for the treatment of B16 melanoma: chemotherapy, surgery, and immunotherapy.

The therapeutic effectiveness of surgery, chemotherapy, and immunotherapy alone and in combination were studied in the B16 melanoma model. The sequence of chemotherapy and immunotherapy as adjuvants to surgery proved important: Chemotherapy was significantly better when given before surgery; immunotherapy was more effective when delivered after surgery. The most effective therapeutic regimen was a combination of all three modalities: a single course of chemotherapy preceding surgery followed by immunotherapy.


Inbreeding and canine mammary cancer: a retrospective study.

Using files of the Animal Neoplasm Registry (ANR) in Alameda and Contra Costa Counties, California, we conducted a retrospective study to compare the degree of inbreeding in the ancestry of purebred dogs with mammary and other cancers, and of those without tumors. Wright's coefficients of inbreeding, calculated for all animals in the three groups, ranged from 0.000 to 0.535. The median inbreeding coefficients of the mammary cancer and comparison groups (consisting of other cancers) were approximately twice that of the nonneoplastic group, but neither difference was statistically significant. Dogs with mammary adenocarcinoma and mixed mammary cancer had similar degrees of inbreeding.


High incidence of spontaneous cervical and vaginal tumors in an inbred strain of Brown Norway rats (BN/Bi).

The incidence of spontaneously occurring tumors of the cervix and vagina was unusually high in an inbred strain of Brown Norway rats (BN/Bi). Fifty-four tumors were diagnosed in the cervixes or vaginas of 252 rats. Of the tumors, 7 were squamous cell carcinomas, 4 were leiomyomas, and the rest were sarcomas. These tumors were found in nearly 20% of all female rats that died naturally.


Comparison of the potentiation of specific tumor immunity in mice by Corynebacterium parvum or BCG.

Two independent studies have compared killed C. parvum (CP) vaccine with viable BCG (Pasteur) and BCG (Glaxo) vaccines, respectively, for potentiation of antitumor immunity when injected with irradiated tumor cells into B6D2F1 AND CBA-T6T6 mice. Both studies concurred that, for a given number of irradiated tumor cells, larger amounts (dry weight equivalent) of BCG than CP were required to produce similar degrees of tumor immunity. Evidence also showed that stronger and more protracted immunity was mediated by CP than by BCG.


Spontaneous ovarian tumors in domestic carp (Cyprinus carpio): light and electron microscopy.

Massive abdominal enlargement was discovered in 8 adult carp (Cyprinus carpio) 4-6 years old, living in breeding ponds of carp fisheries in northern Japan. The abdominal enlargements rapidly progressed and the affected fish died within a few months. At necropsy, single or multiple tumors up to 20 cm in diameter were found in the abdominal cavities. Ovarian tissue identified within the tumor capsule in 4 fish supported the impression, based on gross anatomic features, that the neoplasm arose in the ovaries. Histologically, the tumors were composed mainly of various types of mesenchymal cells. In one sample, striated muscle was identified by electron microscopy; in another, squamous cell nests were intermixed with mesenchymal elements. Although some tumors had areas of cellular pleomorphism suggesting a malignant character, no evidence of invasion or metastasis was found. These neoplasms were classified tentatively as dysontogenetic tumors of the ovary, possibly teratoid in nature.


A phase I-II trial of multiple-dose polyriboinosic-polyribocytidylic acid in patieonts with leukemia or solid tumors.

Polyriboinosinic-polyribocytidylic acid (poly I - poly C), an interferon inducer, was administered in multiple doses of 0.3-75 mg/m2 to 26 patients with a variety of solid tumors, 9 with acute leukemia, and 2 with chronic myelogenous leukemia in blast crisis. Forty-four separate drug trials were comprised of various schedules and routes of administration. Toxic reactions included fever (in 66% of the trials), transient elevation of serum glutamic-oxaloacetic transaminase and serum glutamic-pyruvic transaminase (25%), minimal laboratory evidence of coagulation abnormalities (59%), and hypersensitivity (5%). These toxic manifestations did not relate to dose level or magnitude of interferon induction. Poly I - poly C administered iv induced low serum concentrations of interferon in 24/38 trials (63%), but the correlation between drug dose and peak interferon titer was not linear. Poly I - poly C administered iv or im was not effective as an inducer of interferon in the cerebrospinal fluid. Similarly, poly I - poly C administered im or by inhalation did not produce detectable serum levels of interferon. No patients experienced an objective tumor response to the administration of poly I - poly C, and most (76%) had progression of their disease while receiving the drug.


Glycoproteins on the surface of neuroblastoma cells.

Three neuroblastoma systems were used to define fucose-containing glycopeptides on the cell surface and to relate them to the phenotypic expressions of neuronal functions. These systems were a) clonal lines of mouse neuroblastoma C-1300, b) cell hybrids of mouse neuroblastoma and rat glioma, and c) human neuroblastomas, primary cells from the tumor, and cell lines. The results suggest that similarities exist in the membrane glycopeptides available at the surface of the mouse and human cells. It is proposed that these similarities correspond to the ability of the cells to perform the differentiated functions of neuronal cells or to exist as tumors. Based on analogy with other cell membranes, a schema is given for the structure of the membrane glycopeptides on the neuroblastoma cell.


Cell kinetics and chemotherapy in neuroblastoma.

The proliferative behavior of neuroblastoma cells in bone marrow was evaluated before and after perturbation by chemotherapy. The data presented indicated that the proliferating fraction of the tumor cells before therapy was small. In most of the patients, initial therapy with a non-cell-cycle specific agent increased the mitotic and labeling indices. If initial therapy was followed by a cell cycle-specific agent, variable kinetic responses were observed. Although the number of patients was small and the follow-up was short, there was a correlation between the clinical response and the kinetic changes induced by the chemotherapy. Evaluation of cell kinetic changes during the initial course of chemotherapy might identify early those patients who are unlikely to have a good clinical response. Similar studies in the evaluation of new drugs to aid in identifying agents that favorably change cell kinetics and thus therapy for children with neuroblastoma was urged.


Lymphocyte transformation in children with neuroblastoma.

Using a simple fingerstick-whole blood technique, we demonstrated that patients with disseminated neuroblastoma have diminished lymphocyte responses to phytohemagglutinin (PHA) and that their sensitivity to antilymphocyte serum inhibition of PHA responses was increased over that of tumor-free controls. These altered immunologic reactivities led us to question the chronologic sequence between the occurrence of the tumor and the lymphocyte defect. Tumor-bearing patients had serum substances that exerted an inhibitory effect on the transformation responses of lymphocytes from unrelated normal individuals; these substances may be present in sera for long periods after the tumor is eliminated.


Immunotherapy and chemotherapy in children with neuroblastoma.

Recent advances with immunotherapy in animal tumors suggested that trials with a combination of chemotherapy and immunotherapy in human malignant tumors might be worthwhile. A pilot program with Vibrio cholera neuraminidase-treated tumor cells plus BCG was tested in 3 patients who had had chemotherapy for disseminated neuroblastoma. Two of these children were in "complete remission" after radiation therapy and chemotherapy before the administration of immunotherapy. Relapse occurred in 5-6 months in all 3 patients. These disappointing results are discussed in relation to problems of current chemotherapy in disseminated neuroblastoma including results obtained at second-look operations in patients obtaining "complete remission."


Reactions to dinitrochlorobenzene in patients with neuroblastoma and survival.

To determine the relationship of cell-mediated immunity (CMI) to survival, I studied 67 children with the histologically confirmed diagnosis of neuroblastoma. CMI was measured by testing the ability of patients to develop sensitization to dinitrochlorobenzene (DNCB) and to respond to challenge. Reactions at the challenge sites were considered positive only when induration and swelling were present. Ninety percent of the patients with localized neuroblastoma and 27% of those with disseminated neuroblastoma were DNCB reactive. This suggested that patients with DNCB-positive reactions have a better chance of survival than those who are DNCB negative. Some patients with disseminated disease were evaluated in longitudinal studies, and alterations in reactivity did occur with changes in disease status and/or chemotherapy. The suggestion was made that this test systme is potentially useful in estimating survival in children with neuroblastoma.


Carcinoembryonic antigen in children with neuroblastoma.

Plasma carcinoembryonic antigen (CEA) was assayed with a radioimmune procedure in 27 healthy control children. The upper limit of plasma CEA (mean +2 SD) was derived from healthy controls and was 3.35 ng/ml. This value was compared with those obtained from 15 children with active neuroblastoma, 7 with active embryonal rhabdomyosarcoma, 16 with treated neuroblastoma and without evidence of disease, 14 disease-free patients with embryonal rhabdomyosarcoma, and 17 patients still on therapy. The neuroblastoma and embryonal rhabdomyosarcoma patients with active disease had higher CEA values than did the successfully treated neuroblastoma and embryonal rhabdomyosarcoma patients. CEA plasma values greater than 3.35 ng/ml were found in 35% and 24% of patiens with neuroblastoma and embryonal rhabdomyosarcoma, respectively.


Recrudescence of neuroblastoma after apparent cure.

Many years after apparent cure recrudescence of neuroblastoma was reported in 2 patients. In 1 patient, two recurrences occurred 5 and 10 years after apparent disappearance of tumor. Factors contributing to the extraordinary clinical course are unknown. Speculation rests on tumor characteristics, environmental influences, immunity, or the development of a second primary tumor.


Homologous interference of lymphocytic choriomeningitis virus: detection and measurement of interference focus-forming units.

Lymphocytic choriomeninigitis (LCM) virus defective interfering (DI) particles form foci of protected cells in a monolayer under an agarose-containing overlay medium. Foci originate from one cell dually infected with at least 1 interference focus-forming unit and infectious virus. As a result, an interfering factor is produced and released which interacts with neighboring cells, thereby protecting them against cytopathic lysis by challenge virus. The property of individual LCM virus DI particles to induce countable foci has been made the basis of quantitative assay that is comparable in every respect to the plaque assay of infectious virus and is much more sensitive and probably more accurate than other procedures used to measure LCM virus DI particles. LCM virus was passaged, undiluted, 10 times in cell cultures. When yields were analyzed as to concentrations of PFU and interference focus-forming units, both entities were found to fluctuate with the pattern expected from theoretical considerations.


Interaction of elongation factor 1 with aminoacylated brome mosaic virus and tRNA's.

Tyrosylated Brome mosaic virus RNA was found to interact with a binary complex of wheat germ, elongation factor 1 and [3H]GTP. Increasing amounts of the aminoacylated viral RNA proportionately reduced radioactivity bound to a nitrocellulose filter, as has previously been noted by others for the charged forms of tobacco mosaic virus, turnip yellow mosaic virus, and tRNA's. However, Sephadex chromatography of the products showed that instead of forming the ternary complex elongation factor-GTP-aminoacyl RNA, the viral RNA caused release of GTP from its complex with elongation factor. Acetylated tyrosyl Brome mosaic virus RNA did not react with the binary complex,and only a slight degree, if any, of stabilization of tyrosine bound to viral RNA was observed after interaction with elongation factor 1. Although such interactions are similar to the reaction of elongation factor with aminoacyl-tRNA , the release of GTP is different and accentuates the possible role for aminoacylation in transcription rather than in translation events.


Characterization of ribonucleoproteins and ribosomes isolated from lymphocytic choriomeningitis virus.

Disruption of purified lymphocytic choriomeningitis (LCM) virus with Nonidet P-40 in 0.5 M KCl followed by sucrose gradient centrifugation in 0.3 M KCl led to the isolation of two viral nucleoproteins (RNPs) as well as 40S and 60S ribosomal subunits. The largest viral RNP sedimented heterogenously at 123S to 148S and was associated with 23S and 31S viral RNA. The other viral RNP sedimented at 83S and was associated with 23S viral RNA. The buoyant density in CsCl was determined to be 1.32 g/cm3 for the viral RNP. Densities of 1.52 and 1.60 g/cm3 were determined for the 40S and 60S subunits, similar to those of the BHK-21 cells subunits dissociated by 0.5 M KCl. The viral RNPs were partly sensitive to RNase.


Genetic studies of coliphage P1. III. Extended genetic map.

An extensive genetic map of coliphage P1 has been constructed for 113 amber mutants, using primarily a modification of the conventional complementation spot test. These spot tests failed to classify the mutants into cistrons, but when they were quantitated they permitted assignment of the mutants into 10 linkage clusters. Furthermore, a linear order could be deduced for most of the mutants within each cluster. This strongly suggested that recombination was the predominant event generating plaques and that, for the practical purpose of rapid genetic mapping, such spot tests could be considered as a series of two-factor crosses. Six of the 10 linkage clusters correlated with the P1 genetic map established by Scott (1968). The locations of the remaining four clusters were determined by three-factor crosses and by prophage deletion mapping. The nonrandom occurrence of termini for 14 deletion prophages, which we established previously (Walker and Walker, 1975), and the coincidence of these termini with five out of ten regions demarcating the linkage clusters are discussed. Complementation tests in liquid frequently gave ambiguous results. Therefore, cistron designations were not assigned.


Selection and identification of influenza virus recombinants of defined genetic composition.

The RNAs of influenza virus recombinants were analyzed on polyacrylamide gels under conditions in which the derivation of specific RNA segments (including those coding for hemagglutinin and neuraminidase) could be determined. Analysis of the RNAs of recombinant viruses with identical hemagglutinin and neuramindase revealed that the derivation of the remaining genes could be influenced by UV irradiation of one of the parent viruses. In five of seven such recombinants all of the remaining identifiable genes were derived from the nonirradiated parent, whereas in two others only the three largest RNA segments were derived from the nonirradiated parent. Analysis of the RNA pattern of a recombinant isolated from mixed infection in which neither parent was irradiated demonstrated a random mixture of RNA segments derived from the two parent viruses.


mRNA from the transforming segment of the adenovirus 2 genome in productively infected and transformed cells.

We have identified two mRNA species transcribed from the adenovirus 2 genome section (HindIII-G fragment) believed to harbor genes for initiation and maintenance of cell transformation. The HindIII-G fragment occupies the left 7.5% of the genome and is transcribed from left to right [poly(U:G) r strand]. Poly(A)-terminated labeled mRNA was isolated from polyribosomes of adenovirus 2 early infected KB cells and from the transformed cell line 8617, hybridization purified using the HindIII-G fragment, and electrophoresed on formamide-polyacrylamide gels. Viral mRNA's of 24S (1.2 X 10(6) daltons) and 14S (4.5 X 10(5) daltons) were isolated from early infected cells and of 22S (1.0 X 10(6) daltons) and 14S from 8617 cells. Hybridization competition indicated that HindIII-G-specific mRNA was present in the polysomes at one-sixth the concentration late after infection as compared with early, indicating that the proteins coded by the transforming segment may be synthesized at reduced amounts during late stages. Only 1/10 the amount of RNA labeled late annealed to the G fragment as compared with that labeled early (per weight of RNA). Thus, synthesis of transforming gene mRNA is probably "turned off" late after infection. Both 24S (22S) and 14S mRNA's from infected and 8617 cells were complementary to the Hpa I-E fragment (left 4.1% of genome). The Hpa I-E fragment is too small to encode 24S and 14S species, which implies that the 5'-terminal regions of both species are coded by the same DNA sequences.


Size, subunit composition, and secondary structure of the Friend virus genome.

Electron microscope and gel electrophoresis studies show that the high-molecular-weight (50 to 70S) RNA extract from Friend virus (FV) is a dimer with the same basic structure previously observed for the RNAs from RD-114 virus, baboon virus, and woolly monkey virus. This observation greatly strengthens the inference that the dimer structure is a general characteristic of the RNAs of all mammalian type C viruses. The FV dimer is slightly less stable than the RNA dimer of woolly monkey virus, which is, in turn, much less stable than those of RD-114 and baboon virus. There are three FV monomer components, small (S), medium (M), and large (L), with molecular lengths of 6.7 +/- 0.6, 7.7 +/- 0.6, and 9.5 +/- 0.6 kilobases, respectively. There are approximately equal amounts of the S and M components and much less of the L component. Most of the dimers are homodimers (SS, MM, and LL). The frequency of heterodimers (SM, SL, ML) is much less than expected for a random assortment model.


Multiplication of parvovirus LuIII in a synchronized culture system. IV. Association of viral structural polypeptides with the host cell chromatin.

Newly synthesized structural polypeptides of parvovirus LuIII, VP1 (62,000 daltons) and VP2 (74,000 daltons), were detected in nuclei of synchronized, infected HeLa cells at 11 to 12 h postinfection, i.e., after cells had passed through the S phase of the cell cycle. At this time, most of intranuclear viral polypeptides were associated with the chromatin acidic proteins. However, 13 to 14 h postinfection, about one-third of intranuclear VP1 and VP2 also could be extracted in the fraction containing nuclear sap proteins. According to pulse-chase experiments, VP1 and VP2 accumulated in the chromatin with a time lag of 20 to 30 min. About 90% of these chromatin-associated viral polypeptides represented empty viral capsids. In addition, chromatin prepared at 14 h postinfection contained 90 to 95% of the total intranuclear viral 16S replicative-form DNA. Since viral replicative-form DNA and empty viral capsids seem to be associated specifically with cellular chromatin, we assume that this subnuclear structure is the site of the synthesis of progeny viral DNA and the formation of complete virions.


Read-through proteins of group 4 RNA bacteriophages TW19 and TW28.

Group 4 phages TW19 and TW28 of Escherichia coli possess a "read-through" (IIb) protein, although group 2 phage GA does not. This may have implications concerning the evolution and classification of RNA phages.


Recombination and complementation between temperature-sensitive mutants of a Bunyavirus, snowshoe hare virus.

Complementation and recombination have been observed with temperature-sensitive mutants of Bunyavirus snowshoe hare virus.


Mapping of two isoleucine tRNA isoacceptor genes in bacteriophage T5 DNA.

T5 bacteriophage codes for the synthesis of more than 14 different tRNA species, which map in four separate clusters in the C segment of the T5 chromosome. In this study, two tRNAile isoacceptor species have been identified by reverse-phase chromatography and shown to be transcribed from two different tRNA loci along the T5 chromosome. The map positions of the tRNA isoacceptors were aided by the use of several T5 deletion mutants in which the position and size of the deleted DNA segments had been previously determined by heteroduplex mapping. Hybridization analysis suggests the presence of some sequence homology between the two tRNAile species.


Multiple methylated cap sequences in adenovirus type 2 early mRNA.

The methylated constituents of early adenovirus 2 mRNA were studied. RNA was isolated from polyribosomes of cells double labeled with [methyl-3H]methionine and 32PO4 from 2 to 7 g postinfection in the presence of cycloheximide. Cycloheximide ensures that methylation and processing are performed by preexisting host cell enzymes. RNA was fractionated into polyadenylic [poly(A)]+ and poly(A)- molecules using poly(U)-Sepharose, and undergraded virus-specific RNA was isolated by hybridization to viral DNA in 50% formamide at 37 degrees C. Viral mRNA was digested with RNase T2 and chromatographed on DEAE-Sephadex in 7 M urea. Two 3H-labeled RNase T2-resistant oligonucleotide fractions with charges between -5 and -6 were obtained, consistent with two classes of 5' terminal methyl "cap" structures, m7G(5')ppp(5')NmpNp (cap 1) and m7G(5')ppp(5')NmNmpNp (cap 2) (Nm is a ribose 2'-O-methylation). The putative cap 1 contains all the methylated constituents of cap 1 plus Cm. The molar ratios of m7G to 2'-O-methylnucleosides is about 1.0 for cap 1 and 0.5 for cap 2, consistent with the proposed cap structures. Most significant, compositional analysis indicates four different cap 1 structures and at least three different cap 2 structures. Thus there is a minimum of seven early viral mRNA species with different cap structures, unless each type of mRNA can have more than one 5' terminus. In addition to methylated caps, early mRNA contains internal base methylations, exclusively as m6A, as shown by analyses of the mononucleotide (-2 charge) fraction. m6A was present in the ratio of 1 mol of m6Ap per 450 nucleotides. Thus viral mRNA molecules contain two to three internal m6A residues per methyl cap, since there is on the average 1 cap per 1,250 nucleotides.


Replication of semliki forest virus: polyadenylate in plus-strand RNA and polyuridylate in minus-strand RNA.

The 42S RNA from Semliki Forest virus contains a polyadenylate [poly(A)] sequence that is 80 to 90 residues long and is the 3'-terminus of the virion RNA. A poly(A) sequence of the same length was found in the plus strand of the replicative forms (RFs) and replicative intermediates (RIs) isolated 2 h after infection. In addition, both RFs and RIs contained a polyuridylate [poly(U)] sequence. No poly(U) was found in virion RNA, and thus the poly(U) sequence is in minus-strand RNA. The poly(U) from RFs was on the average 60 residues long, whereas that isolated from the RIs was 80 residues long. Poly(U) sequences isolated from RFs and RIs by digestion with RNase T1 contained 5'-phosphorylated pUp and ppUp residues, indicating that the poly(U) sequence was the 5'-terminus of the minus-strand RNA. The poly(U) sequence in RFs or RIs was free to bind to poly(A)-Sepharose only after denaturation of the RNAs, indicating that the poly(U) was hydrogen bonded to the poly(A) at the 3'-terminus of the plus-strand RNA in these molecules. When treated with 0.02 mug of RNase A per ml, both RFs and RIs yielded the same distribution of the three cores, RFI, RFII, and RFIII. The minus-strand RNA of both RFI and RFIII contained a poly(U) sequence. That from RFII did not. It is known that RFI is the double-stranded form of the 42S plus-strand RNA and that RFIII is the experimetnally derived double-stranded form of 26S mRNA. The poly(A) sequences in each are most likely transcribed directly from the poly(U) at the 5'-end of the 42S minus-strand RNA. The 26S mRNA thus represents the nucleotide sequence in that one-third of the 42S plus-strand RNA that includes its 3'-terminus.


Genome expression and mRNA maturation at late stages of productive adenovirus type 2 infection.

RNA from adenovirus 2-infected KB cells was annealed in liquid with RNA in vast excess to viral heavy (l) and light (r) 32P-labeled DNA strands. Hybridization kinetics were analyzed by computer to estimate the number of viral RNA abundance classes, their relative concentrations, and the fraction of each DNA strand from which they originated. Early whole cell RNA extracted 5 h postinfection annealed rapidly to 10 to 15% of l and r strands and then slowly to final values of 60 and 40% of l and r strands. By 9 h postinfection the expression of late genes was apparent and whole cell RNA annealed to 20 and 75% of l and r strands. Whole cell RNA extracted between 12 and 36 h postinfection annealed to 7 to 15% and 75 to 90% of l and r strands. Late nuclear RNA hybridized to 10 and 90% of l and r strands, and late polyribosomal RNA hybridized to 20 and 75% of l and r strands. Based upon kinetic analyses, we estimate that mRNA synthesized exclusively during late stages arises from about 6 to 8% and 45 to 49% of l and r strands. This assumes that the early class I mRNA (in low concentration late) originates from 8 to 10% and 6 to 10% of l and r strands and that early class II mRNA (in high concentration late) is derived from 2% and 8 to 13% of l and r strands. Mixing experiments indicated that early mRNA is a subset of RNA extracted from polyribosomes late after infection and that late nuclear RNA contains sequences complementary to early l strand class I nRNA. RNA-RNA hybrids were isolated from late mRNA containing sequences from 60% of l and r strands, but it is not known when these were synthesized, and therefore whether complementary RNA transcripts are synthesized late after infection, as they are known to be synthesized early. These results demonstrate that portions of the genome are transcribed into RNA sequences that remain confined to the nucleus and are not exported to polyribosomes as mRNA.


Nature of the single-stranded DNA in replicating adenovirus type 5 DNA.

Single-stranded regions in replicating adenovirus type 5 DNA were isolated and hybridized in solution to the separated strands of adenovirus 2 or 5 DNA. The results showed that the two strands of adenovirus 5 DNA are exposed to almost the same extent during replication, suggesting that displacement synthesis may start from either end of the viral DNA.


Hypernephroma in the solitary kidney: experience with 20 cases and review of the literature.

Twenty patients with renal cell carcinoma in anatomically or functionally solitary kidneys were treated and followed for up to 18 years. Factors pertinent to management and survival of these patients and 66 other well documented similar patients reported in the literature are analyzed. Most of the patients were unusually young and a significant number had had nephrectomy for contralateral renal cell carcinoma. Survival was closely related to the earlier presence of malignant disease in the other kidney, the duration of the interval between detection of the 2 neoplasms and the stage of the lesion in the solitary kidney. Partial nephrectomy has been the most successful treatment. The mean survival in the Mayo Clinic series has been 6 years for patients still alive and 2.4 years for those dead at the time of this analysis. Results in this and other series emphasize the importance of thorough long-term followup after nephrectomy for hypernephroma and of aggressive therapy when the remaining kidney becomes involved. It is foolhardy to abandon hope merely because there is a malignant tumor in a solitary kidney.


Vesicoureteral reflux and end stage renal disease.

Thirty per cent of 50 consecutive patients with end stage renal disease were found to have vesicoureteral reflux. This finding is at variance with the usually published etiologies of end stage renal disease. Forty per cent of the patients with reflux had no history to suggest the presence of this entity. The clinical importance of reflux in the post-transplant period as well as its possible etiologic role in end stage renal disease is discussed.


The surgical fate of ureteral calculi: review of Mayo Clinic experience.

A review of 1,061 patients who underwent ureterolithotomy of transurethral manipulation revealed 2 factors that are important to consider; 1) the roentgenographic size of the calculi measured at the largest diameter and 2) the location of the calculus. These 2 facotrs in addition to the general medical condition of the patient, the duration of severity of symptoms and the status of the upper urinary tract provide suitable guide lines for individual management of ureteral calculi.


Gunshot wounds of the ureter: a 15-year review of 63 consecutive cases.

We reviewed 63 consecutive cases of gunshot wounds of the ureter seen during a 15-year period. The importance of prompt recognition and aggressive surgical management is emphasized, with particular attention being placed on adequate debridement and spatulated splinted watertight ureteroureterostomy. Our philosophy of management for individual injuries is discussed along with our complications and results. This series is the largest reported to date of ureteral gunshot wounds.


Idiopathic rupture of the bladder.

Non-traumatic spontaneous rupture of the otherwise normal bladder is a rare occurrence. The literature is reviewed and 4 new cases are reported. Experimental data are presented and a theory is reviewed regarding the frequent intraperitoneal location of the rupture. The frequent paucity of symptoms compared to the high mortality rate is stressed.


Urine cytology in the detection of bladder tumor recurrence.

Of 118 patients with primary bladder tumors seen since 1966, 73 have been followed with urine cytology since 1969. Of the 406 tests there have been 85 positive, 296 negative and 25 ambiguous reports. The incidence of falsely positive results is estimated at 4% but the incidence of falsely negative results cannot be assessed in this study. Currently, 51 patients are living, 2 of whom had been seen in 1966. Of the 51 patients 43 are being followed with urine cytology. Bimonthly urine cytology has been found to be a relaible, convenient, safe, less hazardous and less costly method for the detection of bladder tumor recurrence.


Partial cystectomy in the treatment of primary and secondary carcinoma of the bladder.

We reviewed 50 patients who had undergone partial cystectomy for primary carcinoma of the bladder. Specific indications and operative technique are discussed. The 5-year survival rate was 67% for patients with stages O and A disease, 53% for stage B and 20% for stages C and D1. Survival was improved for patients with tumors on the posterior bladder wall. Patients in whom free margins of resection were accomplished for unifocal disease had longer survival, with a diminished propensity for developing recurrent bladder cancer. There was no hospital mortality and postoperative complications were minimal. An additional 12 patients underwent partial cystectomy for adjacent carcinomas secondarily invading the bladder with less favorable results.


Non-invasive papillary carcinoma of the bladder associated with carcinoma in situ.

We evaluated 129 patients with low grade, low stage transitional cell carcinoma of the bladder with a minimum followup of 5 years. In addition to the phenomena recognized as indicators of a serious clinical problem (grade greater than I, rapid recurrence, multiple tumors and lamina propria invasion) the identification of carcinoma in situ and/or atypia in normal, incidentally resected mucosa adjacent to the tumor was found to be a positive predictor for subsequent muscle invasion. Ten of 12 patients with carcinoma in situ and 9 of 25 patients with atypia were among 39 who experienced invasion.


Treatment of urethral syndrome with triamcinolone acetonide.

A new method for the treatment of the urethral syndrome is presented. Therapy involves the submucosal injection of triamcinolone acetonide around Skene's glands to decrease inflammation and scarring. It is a simple office procedure, while all other therapeutic modalities are surgical.


Congenital anomalies associated with hypospadias.

We did a retrospective survey on 200 patients with hypospadias to determine what other congenital anomalies were present. The 56 patients with associated anomalies included 16 who had abnormal excretory urograms and 10 of these 16 patients had defects requiring surgical correction.


Urological care of patients with acute spinal cord injury using tidal drainage.

The function of urological care of patients with spinal cord injuries is is 3-fold: 1) prevention of complications until the bladder has recovered, 2) surgical and medical intervention when recovery is not spontaneous and 3) diagnosis and treatment of complications and/or sequelae. Tidal drainage in these patients is easy, convenient, economical, and readily available and adaptable for use at any institution.


Altered bladder function and non-specific epididymitis.

Disorders of bladder function characterized by physiological urethral obstruction were identified in nearly 50% of patients with non-specific epididymitis and anatomically normaly urinary tracts. This association supports the concept that reflux of urine into the ejaculatory ducts may occur and produce epididymitis. The pathophysiology of retrograde urination is reviewed and the predisposing conditions are discussed.


The Doppler stethoscope and the diagnosis of the acute scrotum.

We evaluated 30 patients who had acute scrotal swelling with the Doppler stethoscope. Every case of epididymitis and torsion of the appendix testis demonstrated an increased testicular blood flow. The cases of spermatic cord torsion had no blood flow on ultrasound examination.


The effects of urine on the viability and activity of lymphocytes.

Circulating lymphocytes were incubated for 72 hours in either pure culture medium or a medium-urine mixture in the presence of phytohemagglutinin, concanavalin A or pokeweed mitogen, and assayed for blastogenesis and viability. The amount and osmolality of the urine were varied. Between 80 and 90 per cent of the cells remained viable during the entire study despite the culture mixture. If 50 percent of the culture was replaced by urine at an osmolality of 150, 300 or 500 mOsm, a severe but uniform depression of lymphocyte activity was seen. However, if only 25 percent or less of the medium was replaced by urine at 300 mOsm, the cells stimulated as well as they did in pure medium.


Neuromuscular dysfunction of the lower urinary tract in patients with lesions of the cauda equina and conus medullaris.

Bladder and urethral function was studied in 21 patients with lesions of the cauda equina or conus medullaris using gas cystometry, integrated sphincter electromyography, uroflowmetry and computer assisted measurement of detrusor and urethral innervation. An areflexic cystometrogram, impaired electromyographic sphincter activity and delayed reflex-evoked potentials from stimulation of the detrusor muscle and urethra were the most consistent indicators of lesions of the conus medullaris and/oather than the ice water test is suggested.


A catheter withdrawing apparatus for clinical urethral pressure profile studies.

An apparatus for withdrawing a urethral catheter at a constant speed is described. The motor and the puller assembly are separate components so that the puller assembly can be autoclaved. By matching pulling speed to recorder chart speed a reproducible representation of urethral length can be obtained without using a displacement transducer. The apparatus has been used clinically for measuring urethral pressure profiles.


Complications of vesicoureteral operations from incoordination of micturition.

Recently, a study was made of 8 boys with complications after corrective surgical procedures for dysfunction of the voiding mechanism. One of these patients already had been subjected to irreversible diversion before the basic disorder was recognized but the majority was treated with suggestion (often with hypnosis) as well as with drugs affecting the smooth muscle (1 adolescent was too hostile to accept treatment). Because the bladder was dysfunctional, the operations either failed or sequelae persisted until measures such as suggestion, hypnotherapy and retraining reversed the incoordination of micturition. Operation or reoperation in 5 children might not have been necessary if bladder coordination had been established earlier. The case of boys with poor urinary control but free of neurologic stigmas are suspect. If they require an operation for repair of congenital urinary defects such as reflux, equal attention must be paid to psychologic and habit patterns causing bladder dysfunction. Otherwise, the operation is done essentially into a neurogenic bladder. It is concluded that psychologically conditioned incoordination of voiding may alone produce mid and upper tract damage. The cases of boys with problems of urinary control not explained by neurologic or anatomic defects should be suspected and corrective surgical procedures may fail if bladder dysfunction is not corrected by retraining, suggestion and even hypnotherapy.


Calcified solitary renal cyst in childhood.

There is a 20% incidence of malignancy in renal masses with rim calcification in adults. A case of rim calcification in a solitary renal cyst in a child is presented and the diagnostic approach and surgical management are described. Solitary renal cysts are extremely rare in children, with no reported cases of rim calcification.


Hypertension and post-traumatic renal arteriovenous fistula: demonstration of unilaterally elevated renin secretion.

Ipsilateral elevation and contralateral suppression of renin secretion have been established in a patient with a post-traumatic renal arteriovenous fistula associated with diastolic hypertension. This finding is rare because of the dilutional effect of arterial blood shunted in the renal vein. Increased renin secretion in this instance supports the proposed mechanism of diastolic hypertension with renal arteriovenous fistula.


Anatomical variation of the renal veins with varicosity presenting as pseudotumor of the kidney.

Multiple renal veins opening separately into the inferior vena cava are rare, particularly in the left kidney. To my knowledge there have been no reports of this anatomical variation in the radiologic or urologic literature.


Acute pyelonephritis simulating poorly vascularized renal neoplasm. Non-specificity of angiographic criteria.

A case of acute pyelonephritis associated with venous encasement and amputation is described. Although venous encasement and amputation have been considered previously as specific signs of malignancy, it is now clear that these signs are non-specific, occurring also in inflammatory diseases of the kidney.


Inverted papilloma of the renal pelvis.

A case of an apparently benign urothelial tumor of the renal pelvis is reported. Morphologically, the lesion resembles an inverted papilloma. An article summarizing the findings in 28 of these tumors occurring in the bladder is quoted.


Bilateral simulataneous kidney tumors of dissimilar cell type: a case report with emphasis on operative approach.

The first reported case of bilateral, simultaneous renal tumors of dissimilar cell type treated in a living patient is presented. The operative approach is outlined to support single in situ operative procedures in young patients. A second look laparotomy at 1 year and a creatinine clearance of 60 ml. per minute at 2 years substantiate our enthusiasm for this approach to bilateral renal lesions.


Filling defects in the renal pelvis and ureter owing to bleeding secondary to acquired circulating anticoagulants.

A case of transient filling defects in the renal pelves and ureters, secondary to spontaneously occurring acquired anticoagulants, is presented. The relationship of this entity to hemophilia, immunologic disorders, such as systemic lupus erythematosis, and normal post partum patients is discussed. The differential diagnosis for filling defects in the renal pelvis is reviewed.


Ureteral obstruction owing to endometriosis: reversal with synthetic progestin.

A case of unilateral ureteral obstruction owing to extensive pelvic endometriosis is presented. There was complete resolution of ureteral obstruction following treatment with synthetic progestin. Sequential assessment of renal function was provided by renal imaging and renograms. It would appear that selected patients with obstructive uropathy may respond favorably to medical management, which would allow for preservation of reproductive capabilities and restoration of renal excretory function.


Epispadias associated with phimosis.

proximal to the coronal sulcus-proximal to the cornarl sulcus


Torsion of scrotal testis in a persistent processus vaginalis.

A case of an unusual association between hernia and testicular infarction, namely torsion of a normally descended testis within a persistent processus vaginalis, is presented. The advantages of the inguinal ingulinal approach for the exploration of suspected torsion are discussed. Although an operation was performed more than 30 hours after the onset of symptoms the testicle was viable and recovered.


Klinefelter's syndrome and extragenital seminoma.

An extragenital metastatic seminoma in a patient with Klinefelter's syndrome is described. The increased incidence of many types of malignancies in patients with this chromosomal abnormality and the increased susceptibility of XXY cells to transformation by oncogenic SV-40 virus are discussed. A relationship is suggested circumstantially by these observations.


Hemangioma of the testis in an infant.

Testicular tumors in infants and children are rare and most of them are malignant. Embryonal carcinoma is the most common childhood neoplasm, while seminoma is predominantly found in adults. Hemangioma of the testis is an extremely rare tumor, only 2 cases having been reported in infants.


A new biological assay method for histamine-sensitizing factor using survival time as a response.

A new biological assay method using survival time of mice as a graded response after histamine challenge has been developed for the histamine-sensitizing factor of pertussis bacilli. The method is relatively precise and reproducible in estimation and fairly sensitive in the validity tests of biological assay. Effect of endotoxin on the estimation by the proposed method was also investigated in case the method is applied to the control test of pertussis vaccine.


Studies on delayed-type hypersensitivity to hen egg-white lysozyme. I. Peptide fragments of lysozyme inducing delayed-type hypersensitivity.

Eleven peaks were separated by Carboxymethyl-cellulose column chromatography of peptic digest of lysozyme. Being stronger in antigenic activity two peaks of them, P-3 and P-9, were selected and purified further respectively by Amberlite IRC-50 and Sephadex G-50 column chromatography. As the results, PP-3 and PP-9 were obtained each as a single peak. For estimation of their capacities to induce delayed-type hypersensitivity, the antigen-induced 3H-thymidine incorporation, the migration inhibition of peritoneal cells and the delayed-type skin reaction were tested in guinea pigs immunized with native lysozyme or any of its fractions. PP-9 was almost as active as intact lysozyme in these capacities. On the other hand, PP-3 showed a slight inhibition of migration of peritoneal cells and no stimulation of 3H-thymidine incorporation into the lymph node cells. Moreover, the delayed-type skin reaction elicited by PP-3 was always weaker than that elicited by PP-9. Guinea pigs immunized with either PP-3 or PP-9 were also tested for these reactions. PP-9 and native lysozyme elicited these reactions in guinea pigs immunized with PP-9, but PP-3 did not. On the other hand, PP-3 and lysozyme elicited these reactions in those immunized with PP-3, but PP-9 did not. The possibility of recognition of two functionally different areas, one for production of the circulating antibody and the other for induction of delayed-type hypersensitivity, on the lysozyme molecule was discussed.


Biological activities of endotoxins from Yersinia enterocolitica.

The chemical properties and the general biological activities of lipopolysaccharide (LPS) and Boivin-type endotoxin obtained respectively by phenol-water and trichloroacetic acid extraction from Yersinia enterocolitica serotypes O3 and O9 were studied. The yield of LPS from the O9 strain was about 10% of the O3 strain possibly because of the lower solubility of O9-LPS in aqueous phase. However, the chemical composition of O9-LPS was similar to that of O3-LPS in the proportions of reducing sugar, glucosamine, heptose, KDO, and lipid A. In pyrogenicity and local Shwartzman reactivity in rabbits and lethality for mice, there was also no difference between O3 and O9-LPS. The anthrone-positive carbohydrate and lipid A contents of Boivin-type endotoxin from O3 were higher than those of the endotoxin from O9. The biological activities of Boivin-type endotoxin from O3 were also remarkably higher than those of the endotoxin from O9. It seems that endotoxin of Y. enterocolitica serotype O3 may play an important role in infection by this organism.


Tolerance and other biological properties of Vibrio parahaemolyticus endotoxins.

Biological properties of endotoxins prepared from three strains of Vibrio parahaemolyticus were compared with reference to commercially prepared Salmonella typhi endotoxin. Endotoxin assays performed in rabbits included dermal Shwartzman reactivity, pyrogenicity, heat stability, and ability to induce tolerance as well as cross-tolerance. Mice were used for endotoxin LD50 determinations. Results showed V. parahaemolyticus endotoxins were similar to that of S. typhi strain O901. Induction of tolerance to V. parahaemolyticus strain 11590 endotoxin resulted in complete cross-tolerance to S. typhi endotoxin, and vice versa. Partial cross-tolerance to S. typhi endotoxin was demonstrated with rabbits rendered tolerant to endotoxin from V. parahaemolyticus strains Sak-3 and FC1011. Absorption spectra, nitrogen, phosphorus and carbohydrate analyses revealed additional similarities between endotoxins from V. parahaemolyticus and endotoxin from a member of the Enterbacteriaceae.