Automatic real time arrhythmia monitoring in the intensive coronary care unit. A prospective study was carried out to evaluate accuracy of a real time computer system for arrhythmia monitoring in a coronary care unit. QRS complexes in 57 continuously recorded 30 minute electrocardiographic rhythm strips from 30 patients were classified by the computer. Blinded interpretation of each beat was made by a cardiologist. A total of 146,638 QRS complexes were classified during the monitoring period of 1,710 minutes. The accuracy rate of computer detection was 99.94%. During this period 67 artifacts were identified as beats. The computer correctly identified 5,467 of 5,729 ventricular premature beats (accuracy of detection rate 95.46%). The incidence rate of false positive diagnosis of beats other than ventricular ectopic beats was 0.1%. The rate of computer accuracy in detecting ventricular premature beats was 93.33% in two patients with atrial fibrillation. In individual patients, computer interpretation did not deviate from the cardiologist's interpretation by more than 1 beat/min. The rate of computer accuracy in detecting supraventricular premature beats was lower (82.45%). The distinctly improved accuracy of computer monitoring of ventricular arrhythmia in a coronary care unit reported is the result of a new algorithm. This approach combines major elements of cross correlation of QRS signals as well as grouping of complexes into families. Normal and abnormal templates are stored and newly detected QRS complexes are matched. The program appears to be sufficiently accurate to warrant further applications.


Double outlet right ventricle: clinical spectrum and prognosis. Patients with double outlet right ventricle can be separated into four distinct groups. In the largest (Group III), patients have a subaortic ventricular septal defect and pulmonary stenosis and clinically resemble patients with tetralogy of Fallot. In the next largest group (Group I), patients have a subpulmonry ventricular septal defect and no pulmonary stenosis and clinically resemble children with D-transposition of the great arteries and a ventricular septal defect. These patients have a high rate of coarctation of the aorta leading to early congestive heart failure, and their overall prognosis is poor. In the next largest group (Group II), patients have a subaortic ventricular septal defect and no pulmonary stenosis. Their presentation is similar to that of children with a large ventricular septal defect and pulmonary hypertension. In the smallest group (Group IV), the ventricular septal defect is uncommitted. Survivors in this group also clinically resemble children with a large ventricular septal defect and pulmonary hypertension. When present, coarctation of the aorta and severe mitral valve abnormalities greatly influence the prognosis in double outlet right ventricle. Although the prevalence of associated cardiac abnormalities is large, asplenia, polysplenia, chromosomal abnormalities and other congenital noncardiac abnormalities occur in only 12.5% of patients with double outlet right ventricle.


Pulmonary vascular disease after systemic-pulmonary arterial shunt operations. More than 1,100 patients underwent a systemic-pulmonary arterial shunt operation at the Children's Memorial Hospital, Chicago, from 1946 to 1974. Of these patients, 294 were studied to assess the presence of pulmonary vascular disease and the time of its occurrence after surgery. They were selected either because lung tissue was available for histologic grading of pulmonary vascular disease (114 patients) or because hemodynamic studies were performed after the shunt operation (180 patients). The shunts, all patent at the time of the study, ranged in duration from 1 month to 23 years. After a subclavan-pulmonary arterial shunt (75 patients) there was little evidence of advatients) pulmonary vascular disease in either histologic C2 of 25 patients) or hemodynamic (1 of 50 patients) studies. After an aortic-pulmonary arterial shunt (44 Waterston, 175 Potts) there was small likelikhood of advanced pulmonary vascular disease with a shunt duration of less than 5 years (1 of 35 histologic, 0 of 27 hemodynamic studies). With a shunt duration of more than 5 years the incidence of advanced pulmonary vascular disease increased significantly (15 of 54 histologic, 17 of 103 hemodynamic studies). A mean pulmonary arterial pressure of 50 mm Hg or greater strongly suggests the presence of advanced pulmonary vascular disease. When a systemic-pulmonary arterial shunt has provided effective palliation with decreased pulmonary pressure there is small likelihood that advanced pulmonary vascular disease will develop, even with a long shunt duration of 20 to 25 years.


Pulmonary vascular disease in complete atrioventricular canal defect. The incidence and time of occurrence of pulmonary vascular disease were studied in 67 children with the complete form of atrioventricular (A-V) canal defect. Advanced pulmonary vascular disease begins to develop during the first year of life, with intimal fibrosis (grade 3 cahnges) noted between age 6 months to 1 year. Vascular dilatation with plexiform lesions (grade 4 changes) can be found by age 1 year. These changes can be found in some patients in spite of hemodynamic findings usually considered to indicate lesser degrees of vascular disease. After age 2 years advanced pulmonary vascular disease is commonly found and may persist after surgical correction of the defects. A similar rapid progression of pulmonary vascular disease was noted in 40 children who had a large ventricular septal defect without A-V canal in whom systemic pressure was transmitted directly to the pulmonary vascular bed. Thirty-six of the 67 children had trisomy-21. No difference was noted in the speed of progression of pulmonary vascular disease between these children and those without trisomy 21. Palliative or corrective surgery should be performed in these patients by age 1 year to prevent development of advanced pulmonary vascular disease.


Unstable angina: comparison of medical and surgical management. Medical versus surgical treatment of unstable angina was compared in a prospective nonrandomized study of 118 patients. Acute transient ST-T wave changes were present during chest pain in all patients. Acute infarction was excluded by serial electrocardiograms and enzyme studies. All patients admitted to the coronary care unit from 1970 to 1975 who fulfilled the entry criteria were included in the study. The starting point for data evaluation was 5 days after hospital admission. Characteristics at entry were similar in 66 medically treated patients and 52 patients who had coronary bypass vein graft surgery. During a mean follow-up period of 23 months in 66 medically treated patients with unstable angina the incidence rate of nonfatal myocardial infarction was 17% and the total mortality rate 21 percent compared with respective rates of 19% and 5.8% in 52 surgically treated patients. In the surgical group 8 patients (15%) had a perioperative infarction and only 2 (4%) had a late infarction; one patient (2%) died at operation. Symptomatic improvement was observed more frequently in the surgically treated group. Sixty percent of surgically treated patients were free of angina compared with 21% of medically treated patients. Eight medically treated patients (12%) required late surgical treatment for persistent severe angina despite optimal medical management.


Treatment of recurrent ventricular tachycardia and fibrillation with aprindine. Twenty-three patients with recurrent ventricular tachycardia or ventricular fibrillation, or both, were treated with aprindine, a new antiarrhythmic agent. It was found that: (1) no patient had a recurrence of ventricular fibrillation after aprindine therapy was begun, except as a terminal event subsequent to the development of acute myocardial infarction and cardiogenic shock or refractory congestive heart failure; (2) 6 patients experienced ventricular tachycardia after the loading dose, but with continued aprindine therapy the ventricular tachycardia was suppressed in 3 of these 6 patients, and a fourth patient was asymptomatic during brief paroxysms of ventricular tachycardia; (3) in 2 patients, aprindine was ineffective and was discontinued; (4) electrical cardioversion was not required in any patient receiving aprindine; (5) premature ventricular extrasystoles were decreased in 18 of the 23 patients treated with aprindine; (6) aprindine was discontinued in 1 patient because of intolerable side effects, although ventricular arrhythmias were suppressed in this patient; and (7) 5 patients died from acute myocardial infarction or severe heart failure while receiving aprindine.


Absorption from the peritoneal cavity: SEM study of the mesothelium covering the peritoneal surface of the muscular portion of the diaphragm. Colored tracers, injected intraperitoneally in mice, are taken up by diaphragmatic lymphatics, outlining their large, terminal cisterns, the so-called lacunae. The lacunae occur exclusively on the muscular portion of the diaphragm. The mesothelium covering non-lacunar and lacunar areas of the muscular portion was examined with the SEM. Mesothelial cells overlying non-lacunar areas are extremely flat, and their boundaries are indistinct. Mesothelial cells overlying lacunae protrude towards the lumen of the peritoneal cavity and have distinct outlines. There are openings or stomata, 4-12 micron in diameter, between them. Some of the stomata overlie a deep pit; others overlie a shallower pit in which the surface of another cell can be seen beneath the opening. It seems likely that the bulk of the fluid draining from the peritoneal cavity passes through these stomata into underlying lymphatic lacunae.


A histochemical study of aldehyde fuchsin-positive material and "high-esterase cells" in the pineal gland of the Mongolian gerbil. The pineal gland of the Mongolian gerbil consists of a superficial gland, stalk and deep pineal. The deep pineal differentiates postnatally. Histochemical studies of the superficial pineal gland indicate that it may be involved in the secretion of protein. Presumptive secretory material visualized by aldehyde fuchsin (AF) and chrome hematoxylin was observed along the course of blood vessels and among the pinealocytes. The distribution and texture of the AF-positive material was distinctive. It did not correspond to the pattern and texture of material stained with PAS, Sudan Black or acid orcein. Staining with AF was markedly reduced after incubation with trypsin, indicating that the AF-positive material is at least partially protein. The amount of stainable material increased with age. The AF-positive material was observed in what appeared to be interstitial or glial cells and processes, and in the processes of perivascular cells. Cells and fibrous processes with high non-specific esterase activity ("high-esterase cells") were observed among the pinealocytes and along the course of blood vessels. The distribution of the "high-esterase cells" and the morphology and texture of their esterase-containing processes were remarkably similar to the morphology and distribution of the material that stained with AF. It may be that the "high-esterase cells" contain AF-positive material. The "high-esterase cells" hydrolyzed both alpha-naphthyl acetate and alpha-naphthyl butyrate. The pinealocytes hydrolyzed only alpha-naphthyl acetate. The "high-esterase cells" appear to form a distinct class of cells within the superficial pineal gland. They are tentatively identified as a type of glial cell.


Esterase reactions in acute myelomonocytic leukemia. Specific and nonspecific esterase reactions of bone marrow cells from 14 patients with untreated acute myelomonocytic leukemia and six patients with acute histiomonocytic leukemia were examined. The technic for esterase determination permitted simultaneous visualization of both esterases on the same glass coverslip containing the marrow cells. In cases of acute histiomonocytic leukemia, monocytes, monocytoid hemohistioblasts and undifferentiated blasts stained intensely positive for nonspecific esterase, using alpha-naphthyl acetate as the substrate. No evidence of specific esterase activity using naphthol ASD-chloroacetate as the substrate and fast blue BBN as the dye coupler was apparent in these cells. In all of the cases of acute myelomonocytic leukemia, both specific and nonspecific esterases were visualized within monocytes, monocytoid cells, and granulocytic cells that had monocytoid-type nuclei. Nonspecific esterase activity was not observed in polymorphonuclear leukocytes in cases of myelomonocytic leukemia. The results support a current viewpoint that acute myelomonocytic leukemia may be a variant of acute myeloblastic leukemia, and that cytochemically, many of the leukemic cells in myelomonocytic leukemia share properties of both granulocytes and monocytes.


Development and evaluation of an individualized patient education program about digoxin. A study was undertaken to (1) develop an individualized audiovisual patient education program about digoxin and congestive heart failure, and (2) ascertain whether a patient who received the education program from a pharmacist would demonstrate a significantly greater gain in knowledge about digoxin and congestive heart failure than a traditionally-educated patient. The education program consisted of a slide/tape audiovisual presentation which was reinforced by the pharmacist presenting the program at the patient's bedside. Each patient was randomly assigned to either the study group or control group of patients. A 27-question pretest was given to both the control and study groups of patients to determine their baseline knowledge of congestive heart failure and digoxin therapy. Only the study group of patients received the individualized education program. All patients were then given a posttest to determine the degree of learning that took place during their hospital stay. The patients who received the individualized digoxin education program from a pharmacist demonstrated a significantly greater gain in knowledge about digoxin and congestive heart failure than traditionally-educated patients. It is suggested that hospital pharmacists should deliver an individualized education program to patients taking digoxin during their hospital stay.


Cytogenetic nomenclature.

Cytogenetic nomenclature. The advantage of a standardized nomenclature is apparent in any discipline. A standardized method for designating carbon molecules in steroid chemistry facilitates communication in endocrinology; consistent staging methods permit comparison of data in oncology. Likewise, a standardized method for designating cytogenetic data facilitates communications in genetics. Therefore, investigators should adhere to the official recommendations summarized in this report.


Amniotic fluid fibrinogen degradation products in the prenatal diagnosis of neural tube defects. Elevated levels of fibrin(ogen) degradation products (FDP) have been detected in second-trimester amniotic fluid in association with open neural tube defects (NTD'S) in the fetus. The FDP assay has been proposed for the prenatal diagnosis of NTD's and in this paper is compared with the established use of the alpha-fetoprotein (AFP) assay. FDP and AFP levels were measured in 132 amniotic fluid samples, including 20 NTD cases. The false negative and false positive rates for the FDP assay are high compared with the AFP assay, but it may be of value as an adjunct assay to reduce the over-all false positive rate.


Palliative resections in the treatment of primary colorectal cancer. Seventy-eight patients underwent palliative resections for adenocarcinoma of the colon or rectum. The operative mortality was 6.4 per cent. The high morbidity rate of 43.5 per cent, mostly attributable to errors in operative technic and sepsis, could  not be related to the extent of tumor spread. In fifty-nine patients long-term follow-up revealed a mean survival time of 12.4 months and a median of 9.1 months. Thirty-eight patients (64.4 per cent) survived six months, twenty patients (33.8 per cent) one year,  seven patients two years, and one patient five years. Patients with only local extension of disease had the most favorable duration of survival. Hepatic or peritoneal involvement alone did not preclude long-term survival, but with the two combined the outlook was less favorable. There is a small group of patients with extensive metastatic disease who will not benefit from resection. Otherwise, adenocarcinoma of the colon or rectum with local or distant metastases should be resected when feasible.


[The queen technic for ant control. I. The effect of tepa on laboratory colonies of the pharaoh ant]. The present paper discussed at the example of Tepa [Tris (1-aziridinyl) phosphine oxide] in which manner the control of pharaoh's ant in the sense of the "queen technique" with chemosterilants is possible; which points of view must be considered and which condition an acceptable substance should be fulfilled. The application of Tepa is ralized according to various techniques (e.g. dipping, baiting, tarsal contact), in the course of which the baiting technique is preferred. The influence of different concentrations in various baits on the brood, workers and queens are described. In baits with 1% of the substance a permanent sterilization could be achieved. In combination with other population depressing factors (larval and worker mortality) resulted in eradication of the colonies. The action extended also to the larvae of the sexuals, so that the queenless colonies failed in the production of new queens and males. Histological investigations showed in the females at higher concentrations distinct pathological alterations (pycnosis, vacuolizations, proliferation in the follicles epithelium); whereas the spermatogenesis in the males is decreased but not entirely suppressed. At lower concentrations only the fertility but not the fecundity was influenced. A handing-over of recessive lethal mutations to the progeny does not take place. The practical points of view for the use of chemosterilants in the control of pharaoh's ant are discussed. Whereas the low biological stability of Tepa does not exclude an introduction in the practice, the high mutagenic activity prevents an application in the field.


[Studies of the time of effectiveness and the characterization of compounds in insecticide tests with Aedes aegypti]. The contact-toxicity of 5 insecticides (2 chlorinated hydrocarbons, 2 organophosphate compounds 1 P-substance) are tested against Aedes aegypti L (adults). Because of the relationship between dosage (quantity of application) and time of effectiveness of a compound, we are able to design a specific curve of time-efficacy of each insecticide at graded intervals (= increasing dilutions). This curve may be characteristic of different pure compounds--possibly in connection with other features. The time measurement as a quantitative response was chosen according to the directions of Finney 1952 (mean time to response--dosage). The simple statistical analysis was possible after continuous observation until response-metameter as criterion for time of bioassay = time of exposure. Transformation into complete records (Finney) in feasible with a long period of observation, corresponding response-metameter, extreme values etc. This was found to be the only way to obtain a statistical analysis without complications, and only a few parameters in this model. For statistical evaluation of the differences of the mean reaction times for each dilution of DDT, gamma-BHC, Methylparathion and Trichlorofon the U-test according to Mann & Whitney has been applied. Percentages of 'inactivity' at each dilution are added (decreasing from D7). --The curve of time--efficacy is described, and the possibilities of characterization and indentification of the compounds discussed. General features of ET 50 values and mean reaction times are pointed out, and also the relation of time to response (= exposure time) and dosage, expressed by a simple hyperbolic equation (Haber's formula). The uptake of insecticides by "self-dosine" of insects (as practised in this bioassay) is the closest approximation to natural conditions, but the real dose is unknown [and will depend on the physiological condition of the insects]. Some values with Aedes aegypti (whole activity of the pure compound of each test object labelled with radioactive Trichlorfon) are added (exposure on 1 per cent deposite of insecticide).


[Determination of the frequency of Y-chromatin positive spermatozoa in relation to the parameters of spermiograms]. The percentage of y chromatin positive spermatozoa had been determined using the fluorescence microsopce technique. After staining procedure with Atebrin we counted 44.1 (+/- 3.9)% y poistive sperms, after staining with Quinacrine mustard the amount was 48,4 (+/- 4,3)%. With statistical methods we examined the correlation of the percentage y sperms to the single parameters of the semen analysis. So the sperm count, the motility, morphology, pH and fructose of seminal plasma had been compared with their influence upon the X-Y relationship of spermatozoa. In conclusion of our results there was no considerable variability in the X-Y sperm ratio by the different parameters of the semen analysis.


Transvesical prostatic adenomectomy: a modification of Lower, Harris, and Hryntschak techniques. A review of 226 transvesical prostatic adenomectomies performed by a modification of Hryntschak's technique over a 13-year span is presented. The technique incorporates closure of the vesical neck with transverse sutures of 2-0 plain catgut around a plastic Foley catheter and primary closure of the cystotomy following routine adenoma enucleation. Hemostatic suturing of the posterior vesical neck before placement of the transverse vesical neck sutures is routinely omitted. The results have been uniformly good with low incidence of mortality and morbidity. The average operative blood loss was 761 ml and postoperative bleeding was minimal. This technique is safe, simple and requires an acceptable operating time.


Hydrodynamic radii versus molecular weights in clearance studies of urine and cerebrospinal fluid. The protein permeabilities of the blood-cerebrospinal-fluid barrier and the blood-urine barrier are compared. In both instances the permeation rates of proteins can be better correlated to hydrodynamic radii than to molecular weights. The decreasing clearance rates of ceruloplasmin, IgG, and IgA reflect the hydrodynamic heterogeneity of these proteins, which have similar weights. The IgM clearance rate appears too high, possibly owing to monomer IgM, other IgM fragments, selective transport, or active immunity, so its inclusion is not recommended in clearance studies.


Structure and function of alpha-fetoprotein. AFP is one of several oncofetal proteins synthesized in large amounts by the fetus. Although synthesis drops markedly shortly after birth, small amounts of AFP continue to be produced in the adult. The function of AFP is unknown, but recent studies suggest the possibility that it may have immunoregulatory properties and/or may influence cell proliferation and growth. The high affinity of AFP for estrogen could have important biological functions, although the significance of this binding has not yet been clearly defined. Elevated levels of AFP are seen in a variety of clinical situations, including pregnancy; hepatic disorders, especially chronic hepatitis; and various malignancies, particularly hepatomas, teratomas, and those of primitive gut origin. It is also produced in murine GVH reactions and in lymphomas, both in mice and humans. In human and murine lymphomas, and murine GVH reactions, the presence of AFP-positive cells and immune suppression are highly correlated, but the role of these in the pathogenesis of the diseases is as yet unclear. It appears, however, that AFP may be produced locally in lymphoid tissues involved in GVH and lymphomatous disease without elevations in serum AFP levels. It is speculated that the local production of AFP in these situations may result from blastogenesis of lymphoid cells directed against foreign tumor or viral antigens. AFP could promote the development of tumors either by suppressing immune surveillance and/or immunity to oncogenic viruses, although this is speculative. Finally, the AFP elevations in maternal serum and amniotic fluid are valuable diagnostically in the detection of fetal abnormalities, particularly neural-tube defects.


Mixed connective tissue disease syndrome. Fifteen patients with epidermal nuclear staining on direct immunofluorescence of normal skin and high titer serum antibody to ribonuclease-sensitive extractable nuclear antigen (ENA) had diffuse nonscarring and focal alopecia, abnormal pigmentation, swollen hands with sclerodactyly, and chronic cutaneous lupus erythematosus (LE) as the most common dermatologic features. Direct immunofluorescence of normal, unexposed skin revealed a particulate ('speckled') epidermal nuclear staining pattern in all 15 patients and subepidermal immunoglobulin deposits in 5. Ribonucleoprotein antibodies in high titer are associated with this characteristic type of epidermal nuclear staining. These findings provide easily detectable markers for a less aggressive subset of LE characterized by distinctive clinical and laboratory features consistent with mixed connective tissue disease.


The assessment of operability of esophageal carcinoma. The extremely poor outlook for patients with esophageal cancer necessitates careful definition of the extent of disease prior to the selection of treatment. Evaluation of regional lymph node involvement may avoid excessive morbidity and identify favorable candidates for aggressive excisional therapy. The role of combined mediastinoscopy and celiotomy in assessing the operability of epidermoid carcinoma of the thoracic esophagus was examined in 30 consecutive candidates for esophageal resection at the North Carolina Memorial Hospital. The prognostic value of combined mediastinoscopy and celiotomy in assessing the operability of epidermoid value in assessing mediastinal extension of carcinoma of the upper thoracic and midthoracic esophagus.


Carcinoma of the esophagus: experience with a philosophy for palliation. The preliminary results of a new therapeutic approach to carcinoma of the esophagus were reported in 1972. The primary objective of treatment should be palliation, with cure an important but secondary goal. Lesions in the upper third of the esophagus are treated by irradiation unless there is severe obstruction or tracheal involvement, in which case colon bypass is carried out. Limited resection and esophagogastrostomy is performed through a right thoractomy and midline laparotomy for middle-third lesions and through a left thoracotomy for lower-third carcinomas. Since 1969, 85 patients have been evaluated, of whom 65 (76%) have been treated according to the new protocol. Thirteen patients with upper-third carcinomas were treated primarily by radiation therapy and 6 by colon bypass. Resection was performed in 45 of the 46 patients with middle- and lower-third lesions. There were 5 operative deaths (9.8%). The quality and duration of palliation have been far superior to that achieved by previous methods of treatment and, perhaps surprisingly, survival rates have improved.


Demonstration of Cryptococcus neoformans in a stained bone marrow specimen. Disseminated cryptococcosis is seen with increased frequency in patients with malignant hematologic disease. Usually the diagnosis rests on spinal fluid studies, and little attention has been paid to the direct examination of a bone marrow specimen. A febrile woman with an advanced histiocytic lymphoma was intensively treated with antineoplastic agents; the antemortem diagnosis of cryptococcosis was suspected from direct examination of the bone marrow and was subsequently confirmed by culture. Visualization of fungi in special stained bone marrow specimens could be useful in the initial examination of febrile patients with neoplastic diseases and/or compromised host defenses, and would permit early institution of specific therapy.


Cytochemical methods for copper. Semiquantitative screening procedure for identification of abnormal copper levels in liver. Three previously described histochemical methods for the localization of copper were examined for applicability in the semiquantitative evaluation copper levels in human tissue. Liver tissue obtained at autopsy was stained using dimethylaminobenzylidene rhodanine, rubeanic acid, and diethyldithiocarbamate procedures. The effects of method and time of fixation, staining, incubation time, and variations in procedures were evaluated. Copper levels in tissues examined were determined using atomic absorption spectroscopy. Each staining method was evaluated for sensitivity, reproducibility, and linearity. The rhodanine method was found to produce the most reproducible results, and a linear relationship between microscopical evaluation of the stain and actual tissue copper levels was observed. It was concluded that the rhodanine copper method is applicable for the semi-quantitative evaluation of tissue copper and provides a satisfactory screening method for the identification of abnormal tissue copper levels.


Basal cell carcinoma with metastasis. Review of literature. Basal cell carcinoma (BCC) is the most common form of skin cancer, accounting for 65% to 75% of all malignant skin tumors. Metastic BCC is very rare--only 109 documented cases have been reported to date. The mean time of survival after metastasis has been reported to be ten months. No effective therapeutic modality is known for its treatment. We are reporting a case of metastatic BCC in which we have found deficiency of cell-mediated immunity. Postmortem studies showed a co-existing squamous cell carcinoma in thelungs, brain, liver, and spleen. The most unusual finding in the postmortem study was evidence of juxtaposition of BCC and epidermoid carcinoma with distinct histologic dimorphism. We speculate that a combination of immunodeficiency and stromal independence is needed for metastases in BCC.


Relaxation techniques in treatment of chronic pain. Four spinal cord injured patients with complaints of chronic pain were treated with muscle relaxation and cognitive alteration of attentiveness to pain. The patients reported pain below the level of the spinal lesion; relaxation procedures were directed to muscle groups above and below the level of lesion. Indices of improvement are the patient's subjective report and the staff observations of behavior during the rehabilitation program. Subjective reports were primarily of less pain and improved mood. Staff observations included better program attendance and improved mood. The implications of this approach for rehabilitation and its relationship to psychological theories of pain are discussed.


[Incorporation of tritiated amino acids into the ultrastructure of the cerebral cortex following phenamine stimulation]. The method of electronoscopic autoradiography has revealed an increased biosynthesis of protein by neuronal and glial cells of the motor cortex of rats under phenamine stimulation. The increased level of incorporation of labelled precursors in the molecular layer of the cortex is likely to be associated with increased accumulation of newly synthetized protein in axo-dendritic synapses due to stimulation of the rapid component of the axonal transport of macromolecules. At the same time, participation of the autonomic protein-synthetizing system in the biosynthesis of synaptic proteins is not excluded. The labelled products were found to localize in the field of the thorn apparatus in processes of the "structural-functional" adaptation of synaptic entrances (A. A. Manina, 1972).


[Demonstration of the argyrophil cells of the major glands in autopsy material]. A possibility of identifying endocrine argyrophil cells of the fundic glands of man by the method of impregnation with argentum after Grimelius in sectional material was studied. The cells detected by this method were found to be enterochromaffin-like (ECL) cells. Enterochromaffin (EC) cells in the autopsy material were not retained. Morphotopographic characteristics of ECL-cells in sectional material and bioptic specimens of the gastric mucosa were identical. One of the manifestations of post-mortem changes was adhesion of specific argyrophil granules contained in ECL-cells.


"Failure to thrive" due to pontine glioma. A 14-year-old boy with a five-year history of diencephalic syndrome was found to have a pontine astrocytoma. We review case reports of five similar children with diencephalic syndrome secondary to posterior fossa tumors. We also describe the clinical features, investigative procedures, and therapy of these tumors. These cases emphasize the minimal neurological findings that may be associated with brain stem gliomas and the need for consideration of these tumors in the syndromes of "failure to thrive," anorexia nervosa, and the diencephalic syndrome of infancy.


Increased ocular and systemic responsiveness to epinephrine in primary open-angle glaucoma. Sixteen patients with primary open-angle gaucoma (POAG) were matched as to age, sex, and race with an equal number of patients with secondary glaucoma. Although initial intraocular pressures were comparable, treatment with topical epinephrine hydrochloride, decreased intraocular pressure more than 5 mm Hg in 14 (88%) of the 16 patients with POAG but in only five (31%) of the 16 patients with secondary glaucoma (p less than .005). Eleven (69%) of the 16 patients with POAG demonstrated premature ventricular contractions during tonography as opposed to three (19%) of the 16 patients with secondary glaucoma (p less than .025). These findings suggested greater ocular as well as cardiac responsiveness to epinephrine in patients with POAG.


Urological problems in aged patients.

Urological problems in aged patients. The major urological problems encountered in geriatric patients are bladder neck obstruction, due to hyperplasia or carcinoma of the prostate in men, and urinary infection and chronic urethro-trigonitis (the urethral syndrome) in women. Senile incontinence is common to both sexes.


[Modified impregnation method for staining apical dendrite and spine (modified Golgi's method)]. A silver impregnation method for the demonstration of apical dendrites and spines in materials long preserved in folmalin is reported. This method is a modified version of Golgi's Silver method and consists of the following procedures: The formalin-fixed tissue blocks were incubated in a solution containing 3% potassium bichromate (150 ml), 96% ethyl alcohol (50 ml), and concentrated acetic acid (50 ml) for 24 hrs. at 37 degrees C, and 4 more days at room temperature after changing the solution twice. The tissue blocks were then kept for 5 days at room temperature in a 5% potassium bichromate solution. After making a thorough rinsing for one day in tap water and three washings in distilled water, the blocks were impregnated for 1/2 to 1 hr. in a 0.5% AgNO3 solution, for a further 4 days at room temperature in a 1% AgNO3 solution, washed three times briefly in distilled water and again impregnated for 4 to 5 days in a 2% AgNO3 solution. Following a thorough rinsing in distilled water the tissue blocks were embedded in paraffin and 50 to 100 micron sections were prepared.


The quatenary structure of Pseudomonas cytochrome oxidase studied by electron microscopy. Pseudomonas cytochrome oxidase (EC 1.9.3.2) was studied by negative staining in the electron microscope. The best resolution was obtained with uranyl oxalate (pH 6.0) as negative stain. Electron micrographs confirm the idea of the dimeric structure of the enzyme. A rough model of cytochrome oxidase was constructed based on different projections of the molecule seen in the electron micrographs. In this model the subunits are identical and sterically equivalent.


Characteristics of tryptophan binding in the serum of the newborn rat. During the very first period of postnatal life, tryptophan is almost entirely free in the serum of rats. This situation is in sharp contrast with the well-known ability of serum albumin to bind the essential amino acid in the adult. Three main factors accounted for the relative lack of binding during the early postnatal life when compared to the adult: (1) the lower concentration of serum albumin, the binding protein; (2) the inhibition of binding by nonesterified fatty acids, which were at a high level in the serum of young rats until weaning, and (3) the decreased number of available binding sites for tryptophan on the defatted serum albimin, whereas the apparent association constant of tryptophan binding to serum albumin was similar in newborn and adult. Since immunological characterization of newborn and adult serum albumins did not reveal a specific fetal serum albumin, we suggest that discrete changes at the association site for tryptophan are sufficient to induce large alteration in the binding capacity of the protein. In contrast to the situation observed in adult rats, serotonin synthesis in the brain of newborn animals is therefore not dependent on the equilibrium between bound and free tryptophan in serum.


[Preparation of paraffin sections for the immunofluorescent analysis of antigens of differing chemical nature]. The author suggests a technique for preparation of paraffine sections from tissues fixed with acetone permitting to detect antigens of various chemical nature, including alpha-fetoprotein, antigens of mouse leukemia viruses, alcohol-soluble antigens of hepatocyte membranes, and some phospholipids.


[Mechanism of the effect of  the midbrain reticular formation on the hypothalamus-hypophysis-thyroid gland system]. The role of the posterior hypothalamic nuclei in the transmission of the influences of the mesencephalic reticular formation upon the thyroid hormone secretion was studied. Stimulation of the mesencephalic reticular formation in anesthetized cats was followed by the excitation of the thyroid hormoone secretion: the content of the blood protein-bound iodine was increased. This effect was eliminated after the bilateral coagulation of the posterior hypothalamic nuclei. These findings confirmed the hypothesis on the leading role of the posterior hypothalamic nuclpeus in the stimulation of the hormone secretion.


[Iodine metabolism in the thyroid gland in chronic uranium poisoning]. The exchange of radioactive and stable iodine was studied for 21 days after the I131 injection in the thyroid gland and the blood of rats against the background of chronic uranium intoxication. The latter was accompanied by a decrease in the number of iodine-transport loci of the gland, as well as of the value of the intrathyroid iodine pool and of the stable iodine concentration in the thyroid tissue. The compensatory reaction of the thyroid gland was expressed in the increase of its mass and the rate of the thyroid metabolism as well.


[Study of the action of phytohemagglutinin on continuous human cells]. A study was made of the agglutinating and growth-stimulating properties of phitohemaagglutinin (PHA) preparations in experiments on continuous human cells (clone line HeLa k-41 and CaVe). PHA and PHA gamma-globulin fraction possessed poor hemagglutination properties against human erythrocytes of A, B and O groups, but expressed marked cytoagglutination properties against HeLa k-41 and CaVe cells. With high PHA doses (100 and 500 microng/ml) proliferation and mitotic indx of the culture cells was lower and the percentage of dead cells and the agglutinin titre in the preparations was greater (1 : 256). With lower PHA doses (5 and 25 microng/ml) the growth was much stronger and the percentage of dead cells lower. The agglutinin titre in the preparations decreased to 1 : 16-1 : 32. PHA gamma-globulin fraction produced the strongest  growth-stimulating action with the least amount of dead cells. However, the agglutinin titre in the preparations remained high (1 : 128). A conclusion was drawn that the action of PHA preparations stimulating and inhibiting the growth of continuous human cells proved to be directly connected with the agglutinin content in the preparations, since gamma-globulin PHA fraction expressed the greatest cytoagglutinating and growth-stimulating action.


[Cultivation of embryonic mouse liver epithelium]. Mouse embryo liver epithelial cells maintained in vitro were connected with each other by highly permeable cell-to-cell contacts, synthesized alpha-fetoprotein and possessed the property of contact inhibition of phagocytosis. Methods of cultivation of these cells are presented in this paper.


Relationship of contact activation cofactor (CAC) procoagulant activity to kininogen. Contact activation cofactor (CAC) facilitates the interaction of factors XI and XII. Patients lacking CAC have a coagulation defect and are deficient in high molecular weight kininogen. The coincidence of these two defects suggests that a single protein may be responsible for both physiologic functions. Immunologic and activity studies have been made on isolated CAC to clarify the relationship between CAC and kininogen. CAC forms a single precipitin line with anti-human kininogen, and antikininogen neutralizes CAC activity. CAC and high molecular weight kininogen show a reaction of identity on immunodiffusion against rabbit anti-CAC. Anti-CAC forms two precipitin lines with normal plasma which can be identified as high and low molecular weight kininogen. Monospecific immunoabsorbed anti-CAC forms a single precipitin line with plasma high molecular weight kininogen and neutralizes CAC activity. Cleavage of kinin fragment from CAC by insoluble trypsin or kalikrein does not proportionally reduce procoagulant activity. CAC neutralized by anti-CAC can release kinins on exposure to trypsin or kallikrein. The results support the conclusions that CAC procoagulant activity is a function of high molecular weight kininogen, that antigenic determinants unique to high molecular weight kininogen are shared by the CAC portion of the molecule, and that the clotting reactions may occur at a site removed from the kinin peptide.


Effects of maternal nutrition on fetal growth and infant development. The results of a food supplementation study conducted in four chronically malnourished rural villages in Guatemala were analyzed to determine possible effects on the study children's early mental and physical development. One of two food supplements, atole and fresco, were given to pregnant and lactating mothers and the infants born to them up to three years of age. The level of supplement received was noted and the subsequent course of the children's development observed. Food supplementation of pregnant mothers was found to correlate with higher weights of their babies at birth. No other major maternal variables--home diet, body height and/or weight, morbidity, obstetric characteristics, or socioeconomic status--could account for this association. At 36 months of age the children who had received a large amount of food supplementation showed a far lower prevalence of growth retardation than did those who received smaller quantities. Again, this correlation could not be attributed to any other major maternal variables. In regard to mental development, food supplementation was found to correlate with better performance in psychological tests beginning at six months of age. At 36 months the correlations were significant in five different tests. The results of this analysis have wide-ranging implications for public health. Given the recognized association between low birthweight and infant mortality, they point especially to the importance of maternal nutrition during pregnancy in programs aimed at reducing this serious problem.


The nurse's role in immediate postoperative care. From the time that a patient leaves the care of the anaesthetist after an operation until he wakes in the ward his physiological state should be continuously and expertly supervised. Postoperative nurses are provided only when the operating theatre has a recovery room. A survey among consultants and nurses in one region showed that many surgical units did not have recovery rooms and that inexperienced ward nurses were often sent to collect patients. The survey showed that most nurses were competent to care for unconscious patients so long as an emergency did not arise. In many hospitals the facilities for the safe nursing of postoperative patients were totally inadequate. The very least that is needed is good communications with the anaesthetist, adequate lighting, and a source of oxygen and suction. Because of the shortage of nurses likely to have to care for postanaesthetic patients early on and to train them accordingly. Nevertheless, recovery nurses, whose sole responsibility is to care for a patient until be has recovered from anaesthesia, should be appointed for all busy surgical units.


Detection and measurement of fetomaternal haemorrhage: serum alpha-fetoprotein and the Kleihauer technique. A raised maternal serum alpha-fetoprotein concentration was taken as an indicator of fetomaternal haemorrhage due to amniocentesis and was used to calculate the volume of the fetal bleed. The alpha-fetoprotein concentration seemed to be a more sensitive and reliable indicator than the established Kleihauer technique and may have further applications in antenatal testing.


Retrograde axonal transport of 125I-tetanus toxin as a tool for tracing fiber connections in the central nervous system; connections of the rostral part of the rat neostriatum. After previous studies had shown that 125I-tetanus toxin is taken up with high efficiency by all (adrenergic, sensory and motor)peripheral nerve terminals and that it is transported retrogradely by intraaxonal transport to the corresponding cell bodies, the present experiments were designed to investigate whether 125I-tetanus toxin could be used as a tool for retrograde tracing of fiber connections in the central nervous system and how the results obtained compared with other available retrograde tracing methods. Three to 12 h after injection of 125I-tetanus toxin into the rostral part of the nucleus caudatus of the rat, heavily labeled nerve cells were found in the substantia nigra zona compacta, in Forel field H2 and parts of the zona incerta, and in specific thalamic intralaminar nuclei (nucleus medialis pars lateralis and nucleus parafascicularis). Moderately labeled neurons were observed in the nucleus ventralis thalami and its dorsomedial part, in the nucleus raphe dorsalis and in the frontal, cingular and occipital cortex. Besides the labeling by retrograde transport, orthograde transport of radioactivity occurred in a striatonigral system. The high sensitivity and reliability of this method, even after injection of very small amounts of protein in a very small volume, represent important advantages over most of the commonly used tracing methods.


Ascending projections of the locus coeruleus in the rat. I. Axonal transport in central noradrenaline neurons. Axonal transport of protein and metabolites of L-[3H(G)]3, 4-dihydroxyphenylalanine ([3H]DOPA) was studied in the central noradrenaline neurons of the pontine nucleus locus coeruleus and was correlated with regional alterations of noradrenaline content following destruction of the nucleus. Unilateral lesions of the locus coeruleus produce a partial depletion of noradrenaline in the ipsilateral hypothalamus and telencephalon, indicating that these neurons project widely to the ipsilateral forebrain. Twenty-four to 48 h following local injections of 50 micronCi [3H]proline, locus coeruleus neurons take up labeled material and transport it, presumably as protein, to ipsilateral structures in the midbrain, diencephalon and telencephalon including the neocortex. Similarly 8 h after injection of 25 micronCi [3H]DOPA into the locus coeruleus, transport of material including catecholamines occurs to ipsilateral diencephalon and telencephalon. Axonal transport of proteins to telencephalic structures is greatly diminished by selective lesions of catecholamine terminals with 6-hydroxydopamine (6-OHDA) and following destruction of the medial forebrain bundle. These results provide further support for the view that noradrenaline neurons of the locus coeruleus nucleus project widely within the neuraxis to ipsilateral structures of the brain stem, diencephalon and telencephalon, including all cortical areas. In addition, evidence is presented for a contralateral projection with a similar distribution. The rate of axonal transport of labeled protein and metabolites of [3H]DOPA including [3H]catecholamines in central noradrenaline neurons is estimated to be 3-4 mm/h and is accordingly similar to that reported for noradrenaline neurons of the peripheral sympathetic nervous system.


[Effect of thyroidectomy on circulating thyroid hormones in dogs administered insulin]. In the blood of intact dogs, insulin increases the labelled thyroid hormones (PBI) by about 30% and doubles the T3 level. In athyreotic insulin-administered dogs, the circulating T4 and T3 remain at more or less unvarying values, the plasma disappearance slope of radiothyroxine is not altered. Such data suggest that without the thyroid gland, insulin has no action on the level of the blood thyroid hormones.


Dimorphic nucleolar organizer regions in the frog Rana blairi. The nucleolar organizer-specific staining procedure, ammoniacal silver (Ag-AS), has been used to study the distribution and size of the nucleolar organizer regions (NORs) in chromosomes of the frog Rana blairi (Mecham, Littlejohn, Oldham, Brown and Brown). The somatic metaphase karyotype of this frog is similar to that of other frogs of the Rana pipiens species complex, numerically (2n=26) and morphologically. Secondary constrictions are detectable in untreated Giemsa-stained metaphase preparations as achromatic gaps in the long arms of a pair of submetacentric chromosomes (no. 10). These constrictions are the only regions which are deeply stained with the Ag-AS method and are thus identified as the nucleolar organizer regions (Ag-NORs). In each of the three individuals, the Ag-NORs as visualized on the homologues are of unequal length.


Use of reduced silver staining to show loss of connections in aged rat brain. A variation of the Fink-Heimer reduced silver technique was used to show the extent of axonal degeneration in the brains of aged rats. Degeneration product was extensive throughout the white matter of the old brains, being most dense in the optic tract, but substantial in fornix, corpus callosum, cingulum, and anterior commissure. There was selective impregnation of hippocampal strata, suggesting that there may be differential atrophy of connections as a function of age.


Comparative studies of the cytostatic action and metabolism of 5-azacytidine and 5,6-dihydro-5-azacytidine. 5,6-Dihydro-5-azacytidine hydrochloride, a chemically stable, soluble analog of 5-azacytidine, has cytostatic activity against mouse leukemic L1210 cells grown in culture, but concentrations on the order of 10 micronM, 10-fold higher, than the parent drug, are necessary to inhibit cell growth. The addition of either cytidine or uridine protected against growth inhibition by 5-azacytidine and 5,6-dihydro-5-azacytidine, whereas thymidine potentiated the cytostatic action of both drugs. Deoxycytidine also enhanced the action of 5-azacytidine but had no effect with the reduced analog. Cell suspensions of L1210 cells were able to phosphorylate 5-azacytidine and, to a lesser extent, 5,6-dihydro-5-azacytidine. In cell-free extracts in the presence of ATP and Mg2+, both drugs were converted to nucleotides but at less than 5% the rate of cytidine. As a substrate for mouse kidney cytidine deaminase, the apparent Km value for 5,6-dihydro-5-azacytidine (33 micronM) is of the same order of magnitude as that for cytidine (37 micronM) but less than that for 5-azacytidine (2.1 X 10(3) micronM). The Vm for deamination of the reduced analog is one-tenth that for 5-azacytidine. 3,4,5,6-Tetrahydrouridine, a potent inhibitor of cytidine deaminase, is more effective in blocking deamination of 5-azacytidine than 5,6-dihydro-5-azacytidine.


An evaluation of leukocyte adherence inhibition in the immunodiagnosis of colorectal cancer. The leukocyte adherence inhibition technique was used to assess cell-mediated immunoreactivity and serum-blocking factors related to adenocarcinoma of the colon or rectum. In the group of 48 patients with confirmed tumors of this type, 36 of 38 had reactive leukocytes and 46 of 47 had serum-blocking factors. Patients whose tumors had been removed surgically, with no sign of recurrence, retained their leukocyte activity for up to 3.5 years in 6 of 6 cases, but only a small proportion (7 of 30) retained blocking factors. In 67 controls (who were patients with nonmalignant gastrointestinal disorders, patients with gastrointestinal tumors other than colorectal adenocarcinoma, patients with other cancers, or healthy volunteers), negative reactions were obtained, with diverticular disease the only prominent exception. The leukocyte adherence inhibition test appeared to be highly sensitive and specific. Application to the immunodiagnosis of colorectal cancer thus seems to be warranted.


Abrogation of resistance to feline oncornavirus disease by immunization with killed feline leukemia virus. Four-week-old specific-pathogen-free cats were immunized with a combined vaccine composed of killed feline leukemia virus and killed feline oncornavirus-associated cell membrane antigen-containing tumor cells. Immunization induced feline oncornavirus-associated cell membrane antigen antibody titers ranging from 1:32 to 1:256 but did not elicit detectable virus-neutralizing antibody titers. Kittens immunized with tumor cells alone developed higher feline oncornavirus-associated cell membrane antigen antibody titers (ranging from 1:512 to 1:2048) than those given the combined vaccine. All kittens were challenged with virulent Dynder-Theilen feline sarcoma virus at 12 weeks of age. Seventy-five % of the kittens vaccinated with combined vaccine and 67% of unvaccinated control kittens developed progressive fibrosarcomas after challenge. By contrast, none of the kittens vaccinated with killed tumor cells alone developed progressive fibrosarcomas after challenge. The combined vaccine did not, however, inhibit the induction of feline leukemia virus viremia.


Induction of morphological transformation in mouse C3H/10T1/2 clone 8 cells and chromosomal damage in hamster A(T1)C1-3 cells by cancer chemotherapeutic agents. Various cancer chemotherapeutic agents including alkylating agents, antimetabolites, and antibiotics or natural products were studied for their ability to produce morphological transformation in the C3H/10T1/2 clone 8 mouse cell line and chromosomal damage in the A(T1)C1-3 hamster cell line following a 24-hr exposure of each agent at different concentrations. Those drugs that were known to be carcinogenic in vivo also produced morphological transformation and chromosomal damage, whereas those agents that have not been shown to be carcinogenic in vivo produced neither transformation nor chromosomal lesions. The concentrations used for these studies were in general similar to those actually reached in the plasma of patients treated with these same drugs for malignant, as well as certain nonmalignant, conditions.


A collaborative clinical study of carcinoembryonic antigen in Japan. A radioimmunoassay for carcinoembryonic antigen with utilization of the so-called sandwich method was established and used for clinical investigation. A collaborative study was made through the cooperation of 34 institutions in Japan, and serum samples from about 400 normal adults, 500 patients with benign diseases, and 1500 cancer patients were assayed. About 90% of the normal adults showed carcinoembryonic antigen levels of under 2.5 ng/ml. The benign disease group showed somewhat higher levels than did the normal group, and the cancer group had levels significantly higher than those of the benign group. The levels were strikingly high in cases of advanced cancer with metastases. The specificity of carcinoembryonic antigen and its antiserum is discussed.


Recovery of cells from induced, potentially lethal damage. The recovery of mammalian cells after a variety of treatments is, in part, governed by the cells' ability to deal with repairable, but potentially lethal, lessions. Kinetics of such recovery show a T1/2 of 10-20 hours after ultraviolet (UV) irradiation and 1.5-2.5 hours after X-irradiation. Recovery after exposure to mechlorethamine and bleomycin (BLM) is similar to X-ray recovery; after methylmethane sulfonate, recovery has components similar to X-ray and UV recovery. The sequential treatments of cells with 43 degrees C hyperthermia and X-rays (or reverse order) modify both the immediate survival after treatments as well as the subsequent recovery kinetics. Very similar results are found after BLM and hyperthermia treatments, suggesting strongly that after exposure to that drug a real repair system is operative. However, although recovery after X-irradiation is similar in vitro and in vivo, after BLM the site of treatment and of recovery strongly influences the magnitude and kinetics of recovery.


Physical-chemical characterization of living cells by laser-flow microfluorometry. A rapid method for the laser-flow microfluorometry determination of nucleic-acid content per cell is presented. A frequency distribution of fluorescence is obtained from suspensions of living cells treated with ethidium bromide directly in their own medium (or calcium-magnesium-free Hanks' balanced solution). For a fixed number of cells, a frequency distribution of fluorescence is obtained as a function of the amount of ethidium bromide progressively added to the suspension until staturation. At any ratio of added dye per unit of DNA, histograms generated from cells stained with this method give results similar to those generated after fixation and staining by the Feulgen technique, both in terms of cell-cycle phases and ploidy-level determination. The present technique requires a minimal amount of material, is instantaneous, and is conducted directly on living cells. Furthermore, dye concentration-dependence studies of mean fluorescence per cell allow determination of association constant and binding process (primary and secondary) between the intact cell and ethidium bromide. Cells which have the same amount of DNA but vary in the amount of RNA and/or chromatin conformation (like G0 and G1) can then be distinguished.


Complete nucleotide sequence of the 5' noncoding region of rabbit beta-globin mRNA. The 5' noncoding region sequence of rabbit beta-globin mRNA has been determined. This region is 53 nucleotides long, not including the A-U-G initiator sequence or m7Gppp "cap" structure. 32P-labeled DNA complementary to the 5' noncoding region was synthesized using reverse transcriptase with the synthetic deoxyoctanucleotide d(G-C-A-C-C-A-T-T) as a "primer". The cDNA produced was then sequenced using a modification of the gel-sequencing technique previously developed for DNA sequencing (G.G. Brownlee and E.M. Cartwright, manuscript in preparation). The sequence obtained was checked by depurination and nearest-neighbor analysis. The known sequence at the 3' end of rabbit 18S ribosomal RNA cannot base-pair extensively with the 5' noncoding region of beta-globin mRNA; however, it does form 6 base pairs around the initiation codon.


Phase II study of 5-azacytidine in solid tumors. A phase II study utilizing 5-azacytidine in the treatment of patients with solid tumors was carried out by the Southwest Oncology Group (SWOG-7208). Of 214 patients entered in the study 191 were eligible and 167 were evaluable. While initially they received 225 mg/m2 iv on Days 1--5 every 3 weeks because of toxicity the dose was subsequently reduced to 175mg/m2 and later to 150 mg/m2. Five partial regressions, 2.6% of the eligible patients and 3% of the evaluable patients, lasting from 28 to 77 days were observed. Sixteen patients 8.4% of the eligible patients and 9.6% of the evaluable patients, had no significant change in their disease for 39--255 days. The major toxicities were myelosuppressive and gastrointestinal with 13 deaths attributable to drug toxicity: 11 due to sepsis and two due to cerebral hemorrhage. 5-Azacytidine induced few favorable responses; those that did occur usually were of poor quality and short duration and were associated with significant toxicity.


Phase II study of 5-azacytidine in solid tumors. One hundred and seventy-seven patients were evaluated after therapy with 5-azacytidine using a dose of 1.6 mg/kg/day X 10 days followed by a maintenance regimen. One hundred and forty-eight of the patients received the drug by rapid iv infusion and 29 received the drug daily by and infusion that lasted between 18 and 24 hours. Hematologic toxicity was significant but transient in both groups. Nausea was severe using the rapid iv infusion and minimal with the slow infusion. Antitumor effect was seen in 17% of the evaluable patients with carcinoma of the breast and 21% of the patients with malignant lymphomas. Occasional responses were seen with a variety of other solid tumors. The responses were transient, and clinically, resistance to 5-azacytidine appeared to develop quite rapidly. No clear-cut difference was seen in response rates or duration of response between the two groups of patients. Cross resistance to other anticancer agents was not noted. It is believed that the drug is only of minimal value as a single agent in solid tumors using either of the methods of administration described.


Complete 3' noncoding region sequences of rabbit and human beta-globin messenger RNAs. The 3' noncoding regions of rabbit and human beta-globin mRNAs, 95 and 134 nucleotides in length, have been sequenced. Furthermore, these and previous studies (Baralle, 1977; Proudfoot, 1976a, 1976b) have established about one half of the 589 nucleotide sequence of rabbit beta-globin mRNA, including all of the noncoding region. These sequence studies took advantage of the plus and minus gel-sequencing procedure originally described by Sanger and Coulson (1975) and recently adapted by G.G. Brownlee and E.M. Cartwright (manuscript in preparation). The human and rabbit 3' noncoding region sequences are extensively homologous, except that the human sequence has an addition of 39 nucleotides as compared with rabbit. This extra sequence may have arisen by gene duplication.


Evolutionary relationships between gag gene-coded proteins of murine and primate endogenous type C RNA viruses. Several low molecular weight proteins of endogenous type C viruses of the RD114/baboon group are compared with the gag gene translational products of endogenous type C viruses of murine origin. The p10 proteins of each virus group are shown to be immunologically and biochemically related, while the p12 proteins of RD114/baboon viruses are demonstrated to share antigenic determinants with murine viral p15. Moreover, highly type-specific phosphoproteins, p15 of RD114/baboon viruses and p12 of murine viruses, are shown to possess very similar biochemical properties. These findings, along with previous studies indicating immunologic cross-reactivity between their major internal antigens, p30, demonstrate that each of the gag gene-coded proteins of murine type C viruses has a analogue in viruses of the RD114/baboon group. The immunologic and biochemical relatedness of their gag gene translational products supports the concept of a common progenitor in the evolution of these endogenous viruses.


Combination chemotherapy with cyclophosphamide, vincristine, methyl-CCNU, and bleomycin in advanced bronchogenic carcinoma: experience with 106 patients. A phase II study was conducted with three different combinations of cyclophosphamide, Oncovin (vincristine), methyl-CCNU, and bleomycin (COMB) in 106 patients with advanced bronchogenic carcinoma of all histologies. The response rates were 27.3% for COMB I (six of 22 patients), 18.2% for COMB II (eight of 44 patients), and 7.5% for vincristine, methyl-CCNU, and bleomycin (three of 40 patients). Complete responses were seen only in the small cell carcinoma group. Duration of remission and overall survival were of significance for the small cell group, whereas survival for the other histologic types comparing responders to nonresponders was of no statistical significance. Toxicity was significant and included nausea and vomiting, neuropathy, and myelosuppression. These drug combinations were disappointing and only in small cell carcinoma was meaningful antitumor activity seen.


Basophil histamine release in patients with hay fever. Results compared with specific IgE and total IgE during immunotherapy. Histamine release from leucocytes was demonstrated in grass pollen hay fever patients on in vitro challenge with extract of Pleum pratense (timothy). No release was found in persons without a history of grass pollen allergy. During preseasonal hyposensitization the following tendencies were found in cell sensitivity to allergen as well as in specific IgE antibody level of serum: an initial increase at the beginning of the therapy followed by a decrease during the pollen season. This is in contrast to untreated hay fever patients in whom an increase or no change at all of cell sensitivity and specific IgE was observed in the pollen season. Immunotherapy, therefore, can prevent such an increase in the pollen season. The mechanism might be due to a depression of the IgE production. In untreated as well as in treated patients the cell sensitivity was found to be significantly correlated to the grass specific IgE determined by RAST but not to the total serum level of IgE estimated by RIST. It seems likely that the sensitivity would be useful for evaluating the degree of allergy in grass pollen hay fever patients treated or not treated with immunotherapy.


Fc receptors on human blood B lymphocytes. The frequency of Fc-receptor positive B lymphocytes in human blood was investigated. Under the conditions used heat-aggregated gammaglobulin binding and EA(ox)-rosette formation labelled the same lymphocyte populations. Using various techniques, double marking and cell separations the proportion of Fc-receptor positive cells within the surface Ig carrying population was estimated to be between 11-8 and 36-2%. The proportion of SIg carrying cells within the population forming EA-rosettes was between 11 and 26-4%. This represents extreme values due to known technical circumstances.


A new index for measuring extrinsic stain in clinical trials. A staining index has been proposed which is simple to use clinically and yet is sensitive enough to detect small changes in staining levels between different groups. Accurate scale drawings from An atlas of tooth form were reproduced. Outlines of the labial and lingual surfaces of all eight incisor teeth were enlarged to scale (magnification X 4) and each tooth face divided into 4-mm squares. All areas of extrinsic stain were drawn by the examiner on the grid system. This method has been tested in three clinical trials and the reproducibility investigated. In 161 duplicate examinations a total of 1,830 stained squares were scored by one examiner, compared with 1,853 squares by the second examiner; the reproducibility ratio was 0.155 and the coefficient of correlation was 0.956. The method proved sufficiently sensitive to record differences in staining levels in groups using two dentifrices; one was a normal commercial product with an abrasivity against dentin approximately two-thirds that of the other paste. The proposed Extrinsic Stain Index provides data which can be analyzed by appling parametric or nonparametric tests.


Interaction in vitro between myocardial cells and autologous lymphocytes and sera from patients with rheumatic carditis. The cytotoxicity of antimyocardial antibodies and peripheral blood lymphocytes from patients with rheumatic carditis on autologous myocardial cells was investigated. Although sera obtained after open-heart surgery from seven out of eight patients with rheumatic carditis were bound to cultures of autologous myocardial cells, they were not cytotoxic. Peripheral blood leukocytes obtained both before and after surgery from one of these eight patients aggregated around and underwent blast transformation when exposed to autologous myocardial cells in vitro, but not after exposure to autologous skin fibroblasts. Only the postoperative leukocytes from another of these eight patients aggregated around autologous myocardial cells in vitro; however, these lymphocytes were also not cytotoxic to autologous myocardium. To investigate the effect of antimyocardial antibodies on myocardial function, antimyocardial antibodies were added to the culture medium of pulsating cultures of mouse myocardial explants. Although antimyocardial antibody from 27 patients with chronic rheumatic carditis and seven postcardiotomy patients had no effect on the pulsation of the mouse myocardial cultures, serum gamma-globulin from a patient suffering from acute rheumatic fever with myocardial involvement first accelerated and then gradually stopped the pulsation of mouse myocardial explants.


Wenckebach (type 1) behavior of ventricular reentry. Electrocardiographic excerpts from three patients demonstrate bigeminy, concealed bigeminy, trigeminy, concealed trigeminy, and Wenckebach's pattern of variation in the coupling interval from sinus beat to ventricular ectopic beat. These diverse manifestations of ventricular ectopy support the hypothesis that reentry in man reflects conduction of an initial impulse, with delay, to cause the coupled reentrant beat.


Computer interpreted fetal electroencephalogram: sharp wave detection and classification of infants for one year neurological outcome. The presence of visually discernible sharp waves (SWs) in the fetal electroencephalogram (FEEG) has been found to be associated with abnormal neurological infant outcome, but no method of programmed SW detection for FEEG was available. In order to develop an algorithm for SW detection, the first and second derivatives for visually identified SWs and non-SWs were examined and five random variables chosen for discriminant function analysis (DFA). The resulting equation, incorporated into program logic along with logic for artifact rejection, produced classifications from 85% to 89% consistent with visual identifications, suggesting that the number of SWs/epoch (NSW) corresponds with visually identified SWs. In addition, in 61 cases using a threshold for NSW derived by DFA, computer recognized SWs were found to be significantly related to the overall visual interpretation of the tracings (P less than 0.005). Finally, NSW alone produced correct classification of 65.5% of infants for 1 year neurological outcome. The overall consistency was increased to as high as 80% using additional FEEG and neonatal data. These findings imply that some forms of brain damage are present before birth and can be detected during labor using FEEG.


[Temporal organization of sleep stages in man]. By fitting orthogonal polynomials to the cumulated occurrences of sleep stages, it is possible to describe in a simple form their general trend, i.e. their temporal evolution, in the absence of cyclic ultradian variations. Thus, stages 1, 2 and 3 can be described by a cubic function, REM stage by a parabolic one, while total sleep itself is linear. The fittings can be performed on a general average or on individual data, allowing completion of the subject's clinical description. The first derivative of the general trends gives the instantaneous trend, which has the form of a probability, that of the occurrence of a given stage at a given moment of the night. The study of normal sleep with this technique reveals new aspects of its evolution as a function of time, and makes it possible to propose and test hypotheses on the reciprocal relations between stages.


Epileptic seizures and abnormal electroencephalographic findings in hydrocephalus and their relation to the shunting procedures. A total of 92 patients with hydrocephalus were studied. The incidence of seizures was significantly greater in the "shunted" group (18.2% in the "non-shunted" and 65.4% in the "shunted" group). All of the shunted patients who had seizures developed them after the placement of the shunt. Left sided focal motor seizures were the commonest focal seizures in the patients with right sided shunts. There was a higher incidence of abnormal EEG tracings in the "shunt" group (47% of the "non-shunt" patients and 95% of the "shunt" group). All types of focal EEG abnormalities, but particularly the slow wave foci, were seen more frequently over the hemisphere which had the shunt, and in more than half these localized to the neighborhood of the shunt itself. It is suggested that the shunt, which may act as a foreign body, may be responsible, at least in part, for these findings.


Individual variations in response of human REM sleep to amitriptyline and haloperidol. The effect of amitriptyline and haloperidol on REM sleep was investigated in healthy human adults, with special attention to individual variations in these drugs' effects. In addition, an investigation was made of the rebound elevation of REM sleep occurring on the following night of partial differential REM deprivation (PDRD), again with emphasis being placed on individual variations in that effect. The administration of amitriptyline in a single oral dose of 25 mg was followed by an inhibition of REM sleep in all subjects. The per cent decrease in REM sleep was found to have a significant negative correlation with the per cent increase in REM sleep following PDRD in individual subjects. The amount of REM sleep during the recovery night following the night of amitriptyline medication tended to correlate with the per cent increase in REM sleep following PDRD in individual subjects. Haloperidol in a single oral dose of 1.5 mg caused REM sleep to augment in some subjects but inhibit in others. A significant correlation was noted to exist between drug-induced change in REM sleep and the per cent increase in REM sleep following PDRD.


[Comparative study of somatic and visual projections on the cerebral cortex of the normal adult rat, the rat enucleated at birth, and the young rat]. A comparative study of somatic and visual projections on the cerebral cortex of the adult of the normal rat or of the rat enucleated at birth, and of the young rat. This study was first designed to examine the developmental features of somate, sensory and visual projections to the rat cerebral cortex, together with their alteration as a consequence of early sensory deafferentation. We were led to a reevaluation of these projectins in the normal adult rat. This study specifically shows that topical projections exist, for both the somatic and the visual system. However, projections that are highly convergent in nature are present over most of the superolateral aspect of the cerebral cortex and we were unable to demonstrate any simple change resulting from early visual deafferentation.


Transcallosally evoked potentials and the EEG in the decerebrate dog: actions of tryptaminergic, dopaminergic and adrenergic agonists. The midpontine decerebrate dog, immobilized with gallamine, was used to determine the changes in the transcallosally evoked potential (TEP) produced by intravenous infusions of various drugs. A total of 50 TEPs, recorded from the g. ectolateralis, was computer analyzed before, during and after administration of the drugs. Changes in the TEP were also correlated with changes in the EEG recorded from the g. ectolateralis. The EEG was analyzed by inspection and amplitude integration (electrogenesis). LSD (30 microng/kg) significantly depressed the TEP, and the effect persisted for at least 80 min. DMT (1 mg/kg) caused a significant and reversible increase in the amplitude of the TEP. LSD and DMT reduced the alpha activity of the EEG and enhanced the amplitude of the low-frequency waves. DMT produced a significant and LSD a marginal increase in electrogenesis. Tryptamine (10 and 20 mg/kg), mescaline (6 mg/kg), methoxamine (0.88 mg/kg) and apomorphine (5 mg/kg) had no significant effect on the TEP or EEG. These results suggest that depression of the TEP is not related to spinal reflex facilitation in the dog or hallucinogenic activity in man.


Event-related cortical desynchronization detected by power measurements of scalp EEG. Changes in the background EEG activity occurring at the same time as visual and auditory evoked potentials, as well as during the interstimulus interval in a CNV paradigm were analysed in human subjects, using serial power measurements of overlapping EEG segments. The analysis was focused on the power of the rhythmic activity within the alpha band (RAAB power). A decrease in RAAB power occurring during these event-related phenomena was indicative of desynchronization. Phasic, i.e. short lasting, localised desynchronization was present during sensory stimulation, and also preceding the imperative signal and motor response (motor preactivation) in the CNV paradigm.


[Radial nerve potential at the wrist of man]. Radial nerve potential was studied at the level of the wrist in 13 normal subjects. Simultaneous recording at the level of the median nerve potentials and of a block of its conduction showed that median activity spreads to the area of recording of radial potentials. However, the radial latency is shorter so that potentials of each nerve can be distinguished. This technique could be applied in current practice.


Computer analysis of the electroencephalographic activity of the Caiman olfactory bulb. Bipolar EEG records of olfactory activity of Caiman sclerops were computer analyzed and the derived power spectral density functions (PSD) were statistically compared by the method of Bendat and Piersol (1971) and Fails and Verlander (1977). These recordings included surface and underwater episodes. The Caiman olfactory EEG may legitimately be divided into four types of activity: a spindle form of high amplitude and long duration (1-3 sec), a spindle of lower amplitude, short duration (less than 1 sec) and significantly lower power generation irregular surface background activity, and an irregular underwater activity. PSD analysis showed a great deal of moment-to-moment variability in both quantity of power generated and the frequency regions containing significant power generation during surface background activity. A statistical comparison of surface background and underwater background activity also showed significant differences.


Statistical detection of individual evoked responses: an evaluation of Woody's adaptive filter. The practical performance of the adaptive filter developed by Woody (1967) and Harris and Woody (1969) is assessed in terms of its ability to distinguish evoked responses from the background EEG. It is concluded that selection of good initial template, in this case the Averaged ER, renders iterations beyond the first doubtful validity in the majority of subjects. It is stressed that where iterations are pursued care should be taken over the choice of a suitable statistic to index the process. Finally, given the efficacy of the cavariance function in detecting the grosser features of ER morphology in individual responses, a single trial approach to the analysis of ERs is recommended.


Microelectrode tip in five seconds. A new simple, rapid, inexpensive method. A method using a oxyacetylene torch flame is described; it makes it possible to obtain easily and rapidly, without skill or special equipment, a tungsten micro-electrode tip in a very few seconds.


Sequential frequency analysis: a method to quantify event related EEG changes. A hybrid method of frequency analysis is described by means of which EEG changes related to stimulus-response tasks have been studied. Frequency analysis was carried out using a bank of 20 analog filters by means of which quantitative spectral data were obtained as a function of time. Storing, averaging and statistical analysis of these time-varying spectral data were performed, using a general purpose computer (PDP 11-20). The method proved to be useful for analysis of the non-stationary properties of EEG changes related to certain behavioural events.


[General trends of sleep stages studied by applying orthogonal polynomials]. In an attempt to describe in a dynamic way the evolution of sleep stages or of total sleep as a function of time, we applied to the totality of stages a method of fitting by orthogonal polynomials. With some precautions, the proposed method is of very general application, in man as in animals. It permits description of the evolution of a sleep stage throughout the night by a simple analytical function; further it allows comparisons and statistical treatment separately for each characteristic of this evolution (level, slope and curvature). Finally, the calculations can be done on a general average of a series of measurements or on individual data.


Dihydrotestosterone-binding protein in cytosols of normal and hypertrophic human prostates, and influence of estrogens and anti-androgens on the binding. Dihydrotestosterone-binding protein was observed in cytosols of the normal and hypertrophic human prostates. Association constant for dihydrotestosterone of cytosol of the normal prostate differed slightly from that of the hypertrophic prostate. However, maximum binding capacity was almost identical in these tissues. No distinct correlation was detected between proportion of glandular constituent and binding characteristics (Ka and maximum binding capacity) in the hypertrophic prostates. Influence of some steroids on the binding with dihydrotesterone was examined. Testosterone, estradiol-17beta, estriol, cyproterone acetate and SK & F 7690 inhibited the binding competitively. However, Sch 13521 did not exhibit any influence on the binding.


On the dye spraying method in colonofiberscopy. Dye spraying method was applied in colonofiberscopy; 111 cases of normal colonic mucosa and 26 cases of ulcerative colitis were examined by this method. Using indigocarmine in this method, we could recognize the fine mucosal changes more easily and clearly and get better information for differential diagnosis. Furthermore, the degree of staining of the mucosa by methylene blue, one of the ultra vital staining dye, is different according to the stage of the inflammatory process of colonic mucosa itself in ulcerative colitis. Namely the stainability of the colonic mucosa is corresponding to the healing process of the disease.


Positioning of a plastic prosthesis under fiberendoscopic control in the palliative treatment of cardio-esophageal cancer. A method is described for non surgical peroral positioning of a plastic prosthesis under visual control in patients with obstructing cardio-esophageal malignancy or with pulmonary-esophageal fistula. The ACMI-F7 small calibre endoscope is well suited for guiding the prosthesis mainly because of easy maneuvrability and sufficient sturdiness to withstand substantial pushing force.


An improved cold punch resectoscope.

An improved cold punch resectoscope. The introduction of an improved cold punch resectoscope is reported. The advantages of cold punch resection of the prostate over electroresection are described. Improvements of other direct vision urethro-cystoscopes are mentioned.


Recent advances in investigations of toxicity of automotive exhaust. The influence of auto exhaust on man's health is difficult to gauge considering the intricacy of human environmental urban stresses and particularly of other air polluting (industrial, domestic) emissions. Epidemiological surveys made in road tunnel employees and in traffic officers have not demonstrated specific effects and have often been complicated by cigarette smoking as a factor. Long-term animal experiments run mostly on small rodents give evidence of little effect of the pathological actions of dilutions such as those encountered in high polluted cities. However the acute toxicity of gasoline exhaust emission is well known and mostly due to carbon monoxide. Considering the different types of cycles and operating conditions of vehicles (gasoline and diesel), auto exhaust gases constitute no more a chemical entity than they show, a definite toxicity. A great number of substances that they contain (nitrogen oxides, aldehydes, antiknock additives, heavy metals, possible catalysts are highly toxic as shown by in vivo and in vitro (mutagenic) tests. Interactions of the components are for the moment ignored or poorly understood. Besides, the evolution of the physicochemical properties and natures of the auto exhaust emission in the gaseous biotope of man under determined conditions of ultraviolet irradiation, temperature, and hygrometry provoke the formation of secondary products such as oxidants and ozone. Several experiments show clearly that irradiation increases the toxicity of auto exhaust significantly. For these reasons, geographical, meteorological, and chronological (circadian and seasonal) factors should be taken into consideration, especially with regard to emission standards.


Studies on the synovia in healthy horses with particular reference to the protein composition. Synovial fluid and blood were collected from 18 clinically healthy brood mares in resting conidition. The following parameters were analysed: total leucocytes, glucose, alkaline phosphatase (AP), lactate dehydrogenase (LDH), total protein, albumin, total globulin, albumin/globulin ratio and electrophoretic protein picture. The serum/synovia ratios were calculated for all parameters. It was considered to be of greater diagnostic value to compare these serum/synovia ratios rather than to look at the individual concentrations in synovia. The results obtained did not materially differ from those in the existing literature. In addition, this study confirmed that small protein molecules could more easily penetrate the synovial membrane than high-molecular proteins.


Kinetics of 3H-testosterone and 3H-dihydrotestosterone metabolism in patients with benign prostatic hypertrophy. Effect of cyproterone acetate. The response of 3H-testosterone and 3H-dihydrotestosterone to the administration of cyproterone acetate (CA) over a period of 5 days was investigated. Both tracers were injected intravenously in patients with benign prostatic hypertrophy. Blood was withdrawn for up to 5 h. Benign prostatic hypertrophy tissue was obtained by transurethral resection. Nine patients served as controls. Eleven patients received 300 mg CA intramuscularly. Cyproterone acetate suppressed testosterone and FSH, but not LH. 3H-testosterone was cleared more rapidly from plasma in the patients given CA presumably due to increased metabolism in the liver. 3H-dihydrotestosterone, however, remained virtually uninfluenced. Moreover, CA did not significantly alter the 3H-testosterone and 3H-dihydrotestosterone uptake and metabolism within prostatic tissue.


Stereology, a new quantitative morphological approach to study prostatic function and disease. Although a considerable amount of quantitative biochemical data of the prostatic gland is available the current morphological information is restricted up to now to descriptive findings. Stereology is the application of mathematical axioms and allows one to quantitate three-dimensional structures from the measurement of two-dimensional cross sections thereof. The stereological techniques provide values for volumes, surfaces and number of tissue and glandular cellular components found within the prostatic gland. Four examples are presented to illustrate how quantitative morphology can be applied to study prostatic function and disease. A stereological model, which provides information on the structure of the prostatic gland is shown for the rat prostate (ventral lobe). The model consists of morphologically defined space and membrane components of the prostatic gland and the glandular cell. The alteration, induced in the glandular cells of the ventral lobe of the rat prostate by administration of a synthetic progestine (ethinyl-norgestrienone) were studied by stereological methods. An attempt was made to quantify the morphological aspects of both, the epithelial and stromal components of the normal human prostate (3rd decade of life) and of benign prostatic hyperplasia. In comparing the stereological data of the glandular prostatic cell in the normal human prostate with that in benign prostatic hyperplasia, a diminished secretory activity of the glandular cell in benign prostatic hyperplasia is indicated. A high volume density of the fibromuscular tissue, as well as an activation of the smooth muscle cell in the fibromuscular tissue is observed in benign prostatic hyperplasia.


Spontaneous, augmentable cell-mediated cytotoxicity with limited target cell specificity in human blood. Nonadherent and nonphagocytic lymphoid cells from human peripheral blood became strongly cytotoxic against 51Cr-labeled chicken red blood cells and cells from an established human myeloma cell line when subjected to repeated cycles of washing in phosphate buffered saline or treated with trypsin or lecithinase. Prior to augmentation the effector cells pass nylon wool columns that remove practically all surface IgG-positive cells, but after augmentation they are retained in such columns. Augmentation does not make them phagocytic or adherent to plastic surfaces. Incubation at 37 degrees C of augmented cells prior to addition on the target cells restores the original nonaggressive state. Morphologically the cells making contact with the target cells are small or intermediate-sized mononuclear cells.


Analysis of the antigenic structure of the thymocyte surface membrane by heterologous anti-thymocyte serum. The surface membrane of rat thymocytes and lymph node cells was analyzed by comparing the capability of different rat cell types and of solubilized and chromatographically separated rat thymocyte membrane fractions to absorb cytotoxic antibodies on rat thymocytes and lymph node cells from a heterologous anti-rat thymocyte serum. The experiments described cause distinct antigenic specificities of the thymocyte membrane to be brought into relationship to structures of defined physio-chemical properties, and thus are an approach of a thymocyte cell surface mapping in antigenic as well as in molecular terms. Futhermore, the data presented allow conclusions on the distribution pattern of single antigenic determinants on different cells or tissues used as absorbents and target cells.


The induction of specific resistance in F1 hybrid rats to local graft-vs.-host reactions: nature of the eliciting cell. A specific state of resistance to local graft-vs.-host (GVH) reactions can be induced in F1 hybrid rats, derived from Ag-B incompatible matings, as a consequence of inoculation with low numbers of parental strain lymphocytes. The magnitude of GVH resistance is markedly and directly dependent upon the number of parental strain lymphocytes used in the pretreatment regimen. The relevant constituents of the resistance-inducing parental cell population are thymus-derived (T) lymphocytes possessing immunologic competence for host alloantigens. B cells, themselves incapable of inducing GVH resistance, adversely effect the induction or display of this effect by T cells.


Nonspecific genetic regulation of antibody responsiveness in the mouse. Four lines of mice were produced by selective breeding for quantitative agglutinin responsiveness to flagellar (f) or somatic (s) antigens (Ags) of Salmonellae: high (H) or low (L) responder lines to fAg and H and L responder lines to sAg. The Salmonellae contained both f and sAgs, the Ag used to perform the selection was the Selection Ag and the other was the Associated Ag. The selective breeding produced a progressive interline separation with an equivalent effect for both Ags. After 15 generations (F15) the level of agglutinin response was about 60 times higher in H than in L responders. About 50% of the phenotypic variation of the character investigated is determined by a group of immune response genes, the rest is due to environmental factors. The nonspecific effect of this group of immune response genes was investigated by measuring the responses to three independent antigens: Sheep erythrocytes (SE), dinitrophenyl-conjugated human IgG (DNP-HGG) and bovine IgG (BGG). The selection for fAg response produced an equivalent modification in the respnsiveness to the Associated Ag (97%) and to BGG (130%). This nonspecific effect was smaller for responsiveness to SE and DNP-HGG, 58% and 41% of the Selection Ag response, respectively. The selection for sAg response produced a nonspecific modification of responsiveness of 94% for the Associated Ag of 74% for BGG and 63% for DNP-HGG. An important exception concerned SE to which an equal antibody response is produced in high and low lines of sAg selection.


A heterophile carbohydrate moiety common to mammalian IgM and erythrocytes detected by chicken IgM antibody. Sequential treatment of chicken lymphocytes with normal sheep serum (NSS), chicken antiserum against sheep erythrocytes (SE) and formaldehyde results in rosette formation with SE. The identity of reactive components and the mechanism of rosette formation has been elucidated. The binding activity of NSS to chicken lymphocytes was ascribed to "natural" IgM anti-species antibodies. Subsequently, chicken IgM anti-SE antibody reacted with sheep IgM bound to the lymphocyte surface, and, following formaldehyde fixation, rosettes were formed by the addition of SE. The reaction of chicken anti-SE antibody was competitively inhibited with a hog blood group substance suggesting that it had binding specificity for a carbohydrate moiety which is shared by sheep IgM and SE. This specificity represented only a fraction of the bulk of chicken IgM anti-SE antibodies and was not manifested by antibodies of the IgG class. The analysis by the above-described "sandwich rosette assay" was extended to chicken antisera against horse, rat and mouse red cells and to normal sera from these species. Cross-matching of chicken antisera, with the normal sera and red cells from the tested species revealed a distinct pattern of cross-reactivities. These results imply that the saccharide epitope which is shared by IgM and red cells has a wide distribution between various mammalian species and may be classified as a new system of heterophile antigens.


Experimental allergic neuritis induced by a basic neuritogenic protein (P1L) of human peripheral nerve origin. Experimental allergic neuritis (EAN) in the peripheral nervous system, without involvement of the central nervous system, was produced in laboratory animals by the injection of a basic neuritogenic protein, P1L, purified from human peripheral nerves. The animals manifested a positive skin test with P1L, and their lymphocytes were found to be transformed in vitro in the presence of this protein several days before the appearance of the clinical signs. Passive transfer of the disease was performed with lymph node cells from donor guinea pigs immunized  with P1L protein. EAN, the experimental model for the human disease Guillaain-Barré syndrome, was shown to be a transient disease and could be suppressed by the administration of hydrocortisone.


Immunofluorescent detection of differentiation alloantigens (CA1) in the chicken. Lymphoid cell surface alloantigens were detected by a triple-layer immunofluorescence technique. An antiserum raised against B locus-incompatible lymphoid cells also reacted with previously undefined differentiation antigens (CA1) which segregated between B locus homozygous (B14/B14) chickens of the same strain as the antiserum donor. CA1-positive chickens reacted with the antiserum by agglutination of red cells and staining of all peripheral lymphocytes and thymocytes but not bursal cells. Cross-absorption experiments have demonstrated that antigens expressed by red cells, T cells (both thymic and peripheral) and B cells (peripheral only) respectively, were of distinct specificity.


Orientation of Giemsa C-bands in interphase cells of Allium cepa L. Orientation of Giemsa C-bands in Allium cepa was studied in both mitotic and interphase cells. It has been shown that telophase orientation of the chromosome is maintained throughout the interphase and early phophase. It has been assumed that this non-random orientation is due to anchorage of the telomeres with the nuclear membrane. Contrary to earlier observations, 2 by 2 pairing of the telomers could not be traced to this species.


[Toxic action of lindane. Biochemical and ultrastructural changes in the lysosome system in cultured hepatocytes]. Lindane, in contact with cultured foetal chicken liver cells over a period of 40 hours, has a biphasic action on the lysosomal system of the cells. For the concentrations between 1 micronM and 25 micronM not affecting the cellular growth, the decrease of the acid phosphatase activity and the absence of any reaction in the Golgi saccules might indicate a reduction in the synthesis of the lysosomal enzyme. For the concentrations above 25 micronM slowing down cellular growth, acid phosphatase activity is partialrogeneous content and an increase in the relative acid phosphatase activity in the soluble extralysosomal fraction, for doses over 150 micronM, might indicate the development of the phenomenon of autophagocytosis.


Zinc biochemistry in normal and neoplastic growth processes. Zinc is essential for the growth of all species. Growth arrest results from its deficiency and presumably reflects important roles for this metal at critical points of metabolism. Studies of zinc metalloenzymes show that zinc serves as a coenzyme to more than 80 enzymes, among which are the reverse transcriptases which cause leukemia in many species. Its role in nucleic acid metabolism is emphasized.