Pulsus paradoxus in asthmatic children.

Pulsus paradoxus in asthmatic children. Pulsus paradoxus is a useful physical sign in the assessment of the severity of asthma in adults. Whether this is also true for asthmatic children was determined by measuring respiratory fluctuations in systolic blood pressure during attacks of asthma in 24 children. A decrease in systolic pressure during inspiration exceeding 15 mm Hg was found only when the 1-second forced expiratory volume was less tha 60 percent of the predicted value. There was a highly significant (P smaller than 0.001) correlation between the degree of pulsus paradoxus and the severity of airway obstruction. In nonasthmatic children the systolic pressure was found to fluctuate by as much as 7 mm Hg during the respiratory cycle. It is concluded that, as in adults, the presence of pulsus paradoxus (larger than or equal to 15 mm Hg) in children indicates that their asthma is very severe.


Solitary thyroid metastasis from clear-cell renal carcinoma. A 58-year-old woman underwent nephrectomy because of clear-cell renal carcinoma. Seven years later a solitary thyroid metastasis was detected. She is alive and well 17 months after thyroidectomy. The rarity of this manifestation is well known but its explanation is not clear. The long metastasis-free interval, a characteristic shared by other hormonally dependent neoplasms, has been explained in part by the concept of "dormant cells", which do not undergo division. The stimulus that provokes these cells into division is at present not known.


Follicular carcinoma of the thyroid with functioning metastases and clinical hyperthyroidism. Hyperthyroidism associated with metastatic follicular carcinoma of the thyroid gland is rare. In one patient the mass of functioning follicular tissue in the primary and metastatic tumour was so great that excessive amounts of thyroxine and triiodothyronine were produced and, as a result, clinical hyperthyroidism developed. This was in spite of the fact that the activity per unit of tissue was not supranormal and may even have been slightly subnormal. The initial response of the metastases to 131I ablative therapy was excellent.


A clinical look at the problem of drugs in pregnancy and their effect on the fetus. The first annual W. E. Upjohn Lecture concerned itself with the interrelationship between administration of drugs to the pregnant woman and fetal outcome. The epidemiology of drug intake (both prescribed and self-administered drugs) during pregnancy is reviewed, using data derived from several surveys conducted both in the United States and in Scotland. The complexities of establishing a causal relationship between drug intake during pregnancy and effects upon the fetus are considered. Special emphasis is given to the adverse effects of aspirin and cigarette smoking. The shortage of data is critical and the need for further research is stressed.


Excretion of inhibitors of calcification in urine. Part I. Findings in control subjects and patients with renal stones. The total excretion of inhibitors of in vitro calcification was measured (in inhibiting units per day) in 24-hour urine samples of 11 control subjects and 20 patients with renal calculi. A semiquantitative method incorporating the rachitic rat cartilage technique was used. In both groups there was a significant positive correlation between the number of inhibiting units per day and the daily urine volume. The mean number of inhibiting units per day was significantly (P smaller than 0.05) higher in the stone patients than in the controls. However, the stone-formers had significantly larger (P smaller than 0.01) 24-hour urine volumes. When corrections were made for urine volume there was no significant difference between the two groups. These data suggest that the underlying abnormality responsible for renal stone formation is not a persistent decrease in the total concentration of urinary inhibitors of calcification.


Diagnostic differences in psychogeriatric patients in Toronto, New York and London, England. National statistics on psychiatric illness in the elderly patient from Canada, the United States and the United Kingdom suggest great differences in morbidity in these three centres. The present study shows that these differences stem mainly from different diagnostic habits in the three countries, but also there were more alcoholics in the Canadian sample. In particular, the diagnostic bias of the New York psychiatrists towards diagnosing most elderly patients as senile was not shared by their Toronto colleagues. Some patients were psychiatrically well, in spite of receiving a psychiatric diagnosis, and could have been helped without hospitalization. In addition, some depressed patients were labelled senile. Recommendations include improvement of catchment and treatment facilities for the elderly alcoholic and the provision of psychogeriatric diagnostic centres.


Esophageal achalasia associated with gastric carcinoma: lack of evidence for widespread plexus destruction. Achalasia of the esophagus occurred in association with gastric carcinoma involving the cardia. Except in a limited area subjacent to the squamocolumnar junction, the pathologic findings were unusual in that the myenteric plexus of the body of the esophagus was intact and apparently uninvolved. The hypothesis is advanced that, in this instance, the achalasia could be classified as a tumour-associated funnctional disorder due to distant neural involvement rather than to local invasion with plexus destruction.


Fatal self-poisoning with lithium carbonate. In a fatal case of self-poisoning with lithium carbonate there was a progressive increase in serum lithium concentration for 48 hours after ingestion of the overdose. It is suggested that the continuous increase in serum lithium concentration reflects prolonged absorption of lithium from relatively insoluble aggregates of lithium carbonate in the gastrointestinal tract. In this case there was an interval of 45 hours between ingestion of the overdose and the onset of central nervous system depression. Simultaneous peritoneal dialysis and hemodialysis were effective in rapidly reducing the serum lithium concentration but there was little concomitant change in the patient's level of consciousness. The terminal event was a respiratory complication of the comatose state.


Iliacus hematoma syndrome.

Iliacus hematoma syndrome. In a patient receiving warfarin and heparin in the treatment of pulmonary embolism, a hematoma developed in the iliacus muscle, compressing the overlying femoral nerve. Femoral nerve paralysis ensued, causing inability to walk, pain and loss of sensation in the sensory distribution of the nerve. Surgical intervention and removal of the hematoma relieved the nerve compression and the condition gradually improved.


Ultrastructure of two cases of anaplastic giant cell tumor of the human thyroid gland. Electron microscopy of two cases of anaplastic giant cell tumor of the thyroid revealed that these neoplasms consisted of pleomorphic cells with large, bizarre-shaped nuclei and relatively little cytoplasm rich in rough endoplasmic reticulum. The presence of various intercellular junctions, the resemblance of tumor cells to non-neoplastic epithelial cells of the thyroid follicles and the observation that follicular remnants were identified in the tumor, support the assumption that these tumors derive from the follicular epithelium and can be regarded as carcinomas. Aggregates of cytoplasmic spherical bodies, ultrastructurally similar to virus particles, were detected in some tumor cells. Further investigation is required to determine the nature of these structures and establish their pathogenetic role. In some tumor cells, tubuloreticular arrays were noted within the dilated cisternae of the endoplasmic reticulum; these may represent ultrastructural manifestations of nonspecific injury.


Ultrastructure of anaplastic (spindle and giant cell) carcinoma of the thyroid. Three anaplastic (spindle and giant cell) carcinomas of the thyroid were studied by light and electron microscopy; two of the tumors also included foci of recognizable follicular carcinoma. The follicular carcinoma cells desplayed prominent mitochondria and rough endoplasmic reticulum, and showed evidence of secretory activity. Desmosomes and complex cellular interdigitations were evident. Basal laminae were present, with conspicuous reduplication in the well-differentiated foci. However, some epithelial clusters were surrounded by basal lamina, showing focal discontinuities through which epithelial cells protruded into the stroma. The pleomorphic spindle and giant cells showed cytoplasmic and nuclear characteristics similar to the better differentiated carcinomatous follicular elements, but showed rare desmosomes and no basal laminae. The basic ultrastructural similarity between follicular and anaplastic tumor cells confirms their common epithelial origin. However, while partially retaining their secretory capability, the anaplastic cells progressively lose their capacity to synthetize basal lamina and develop complex cellular attachments.


Anaplastic giant-cell carcinoma of the thyroid. A study of treatment and prognosis. In 79 cases of histologically verified anaplastic giant-cell carcinoma, symptoms, treatment, and prognosis were documented. Seventy-eight patients are dead, the mean survival time being 2.5 months. One patient is cured. It was concluded that surgery and/or radiotherapy alone are not sufficient. The results from an additional 8 patients also treated with methotrexate indicate a positive therapeutic effect, the mean survival time being 9.4 months. Disappearance of recurrent tumor or pulmonary metastases was noted in 2 patients.


Nonepithelial tumors of the nasal cavity, paranasal sinuses, and nasopharynx: a clinicopathologic study. IV. Smooth muscle tumors (leiomyoma, leiomyosarcoma). In a review of nonepithelial tumors involving the nasal cavity, paranasal sinuses, and nasopharynx, 256 lesions, 156 benign and 100 malignant, were identified. Of these, 8 were smooth muscle neoplasms, 2 leiomyomas, and 6 leiomyosarcomas. The clinical findings associated with these smooth muscle tumors are described, their histologic features illustrated, results of therapy presented, and clinicopathologic correlations made. The leiomyomas were small lesions found incidentally within polypectomy specimens, and were successfully treated by polypectomy. Leiomyosarcomas could not be eradicated easily by surgery, recurred frequently, did not respond well to radiotherapy, and carried a poor prognosis.


Dopamine-B-hydroxylase and catecholamines in an olfactory esthesioneuroma. In a case of olfactory esthesioneuroma, of which an unfixed specimen and blood sample were available, we demonstrated immunohistochemically and biochemically the presence of dopamine-B-hydroxylase and catecholamines in low concentration. This result indicates that this nasal tumor is probably of sympathetic origin, in whole or in part, and provides a new aid in diagnosis. Furthermore, biochemical assay of dopamine, V.M.A., and H.V.A. excretion in urine could perhaps bring information of diagnostic and prognostic value before and after treatment.


Elevated IGA in carcinoma of the nasopharynx. Fourteen patients with nasopharyngeal carcinoma were evaluated immunologically prior to standard radiotion therapy. All had elevations of serum IgA, ranging from 300 mg/100 ml to 1000 mg/100 ml, with a mean value of 549 mg/100 ml. Seven patients demonstrated depression of cell-mediated immunity as measured by delayed hypersensitivity skin tests, total lymphocyte count, in vitro stimulation with PHA, and T-cell rosette formation. Elevation of serum IgA associated with depression of cell mediated immunity may be characteristic of patients with nasopharyngeal carcinoma.


Low-dose radiation pneumonitis.

Low-dose radiation pneumonitis. A case demonstrating fulminant radiation pneumonitis following a course of prophylactic whole lung irradiation at doses below 2000 rads, resulting in death, is presented. The importance of predisposing factors and the suspected "sensitizing" factor in this case are discussed.


Detection of skeletal involvement in Hodgkin's disease: a comparison of radiography, bone scanning and bone marrow biopsy in 38 patients. As part of the staging of 38 patients with Hodgkin's disease seen over an 18-month period, we have used radioisotopic scanning of bone, as well as radiography and bone marrow biopsy, in an attempt to assess osseous and bone marrow involvement. Of the 38 patients, 14 were found to have skeletal involvement. In 11 this was histologically proved. In 8 patients, the radioisotopic scan first raised the suspicion of localized bone involvement, which was subsequently proved by bone marrow biopsy or by radiography. We believe that bone marrow involvement may at times be localized when patients with Hodgkin's disease are first staged and may precede local osseous involvement. If this is so, a reasonable approach to the search for bone marrow or osseous involvement would be to start with a bone scan and to follow this with a bone marrow biopsy from the suspicious area or a careful radiography of the same site; the latter is important if the site of increased uptake of the radionuclide is inaccessible to the biopsy needle.


Carcinoembryonic antigen in patients with gynecologic malignancy. Carcinoembryonic antigen (CEA) was elevated (greater than 2.5 ng/ml) in 81 of 100 patients with gynecologic malignancy and in 17 of 95 patients with benign gynecologic disease. CEA concentration was, in general, related to the extent of disease, and in early stage cancer often returned to normal following complete surgical excision. Tumors were classified morphologically according to cell type, lymphoplasmacytic infiltration, necrosis, vascular invasion, desmoplasia, and degree of differentiation. The only histologic characteristic associated with elevated CEA levels was the presence of vascular invasion. Further investigation is needed to define the structure, function, and metabolism of CEA in patients with gynecologic malignancy.


Mesocolic lymph node histology is an important prognostic indicator for patients with carcinoma of the sigmoid colon: an immunomorphologic study. Histologic parameters which are thought to reflect either cell-mediated (T cell) or humoral (B cell) immune responses in lymph nodes have been studied in regional lymph nodes draining carcinoma of the sigmoid colon. Patients whose lymph nodes show morphological evidence of cell-mediated immunity, manifested either by an increased number of paracortical immunoblasts or sinus histiocytosis, survive significantly longer than those whose lymph nodes show no such changes. Patients whose lymph nodes show simultaneous paracortical activity and sinus histiocytosis have the best survival of all. Of this latter group, 11/13 (83 percent) are living without signs of recurrent tumor 5 or more years after surgery. Histologic parameters which suggest an antibody-mediated immune response (germinal center activity) were not an important prognostic indicator. The occurrence of favorable lymph node histology does not appear to significantly correlate with the modified Duke's classification. Rather, the favorable changes allow selection of a large proportion of those patients within the various Duke's categories who are destined to become long-term survivors.


Phase II study of procarbazine, CCNU, and vincristine combination chemotherapy in the treatment of malignant brain tumors. Forty-eight patients with primary or metastatic malignant tumors of the central nervous system (CNS) were treated with combination chemotherapy, consisting or procarbazine (100 mg/m2 X 14 days), CCNU (75 mg/m2), and vincristine (1.4 mg/m2 X 2, 1 week apart) (PCV) every 4 weeks. Most patients had undergone initial resection of primary tumors, postoperative radiotherapy, and a post irradiation interval of 3 months or more. Other patients harbored unbiopsied, newly-discovered primary or metastatic tumors. All patients were deteriorating neurologically when treatment began. Overall response rate for PCV combination therapy was 44%, no better than results obtained with single agent procarbazine or BCNU, the most effective drugs used alone in previous brain tumor chemotherapy studies.


Primary rhabdomyosarcoma of the cerebrum. A primary cerebral rhabdomyosarcoma is described in a 48-year-old Negro man. At autopsy two metastatic nodules were present in the liver. A review of the literature indicates that this is a rare and highly malignant tumor with no 5-year survival. The multipotentiality of the mesenchymal tissue in the leptomeninges is considered the histogenetic origin of intracranial rhabdomyosarcomas.


The nitroblue tetrazolium test in patients with advanced neoplastic diseases. The nitroblue tetrazolium test (NBT) was evaluated in 111 patients with cancer. Patients were placed into control and "presumed infected" groups. The mean NBT score for the control group, 6.3, was significantly greater than the mean for a group of normal volunteers, 3.1, but the mean score for the "presumed infected" group, 15.6 was significantly higher. Less than 10 percent of the patients with bacterial infection had scores below 10, while 15 percent of the control patients had unexplained high scores. A method for concentrating leukocytes is described which makes the NBT test feasible in patients with granulocytopenia. Morphological changes in granulocytes used as indicators of infection are unreliable markers in cancer patients, in whom such changes occur frequently in the absence of infection. We have found that the NBT test is more useful as an indicator of infection in patients with cancer.


Lymphoma presenting as bone marrow failure. In reviewing 550 patients with non-Hodgkin's lymphoma, only 3 percent were found to present with severe leukopenia or thrombocytopenia due to bone marrow infiltration. Patients with well-differentiated lymphoma had a favorable prognosis despite the presence of cytopenia. In contrast, individuals with poorly differentiated lymphoma had a median survival of only 4 months. Thus, the critical factor in survival was the degree of differentiation of the lymphoma. Conventional therapy proved of little value in the poorly differentiated group. Trials of intensive multidrug chemotherapeutic regimens seem warranted, despite the risk of exacerbating the cytopenia.


A melanocytic tumor of the esophagus.

A melanocytic tumor of the esophagus. The author describes a heavily pigmented, encapsulated tumor within the wall of the esophagus of an adult male patient. The differential diagnosis is discussed. It is concluded that the tumor is probably benign and of neurogenic origin.


Malignant histiocytosis in a patient presenting with leukocytosis, eosinophilia, and lymph node granuloma. A patient with malignant histiocytosis presented with a number of unusual features including fever, leukemoid reaction, and eosinophilia. Other confusing findings included lymph node biopsies which showed reactive changes, noncaseating granuloma, and atypical Reed-Sternberg cells. These features are compared with cases appearing in the literature. The course was rapidly progressive despite combination chemotherapy.


Hypersplenism in advanced breast cancer: report of a patient treated with splenectomy. A patient with widespread metastatic breast cancer had thrombocytopenia and severe anemia due to splenic hyperfunction, confirmed by chromium51-labeled red cell survival and sequestration studies. Marked splenic enlargement was produced by metastatic tumor. After she failed to respond to steroids, her hematologic status was improved by splenectomy, and has been stable for 16 months. Hypersplenism may be suspected as a cause of severe hemolytic anemia in advanced carcinoma. If the patient's general status is otherwise compatible with long comfortable survival, appropriate diagnostic studies and consideration of splenectomy are warranted.


Generalized melanosis complicating disseminated malignant melanoma in pregnancy: a case report. A case of generalized melanosis complicating disseminated malignant melanoma in pregnancy is described. Four features of this case, unique in combination, are discussed. First, generalized melanosis is a rare complication in macrophages of skin and other areas. Secondly, extensive bone lesions in the absence of roentgenographic changes are an uncommon occurrence. Thirdly, pregnancy probably has little effect on the course of melanoma, as illustrated by this case and a review of the literature. Finally, placental metastases may be more common than generally thought, yet may have little significance to the fetus.


Human thoracic duct cannulation: manipulation of tumor-specific blocking factors in a patient with malignant melanoma. Thoracic duct lymph was drained for 28 days from a patient with disseminated malignant melanoma. Lymphocytes were separated from the lymph by centrifugation, and returned to the patient daily. Biochemical and hematologic parameters were monitored in blood and lymph, and were maintained at satisfactory levels throughout the period. Cell-mediated immunity and specific blocking activity directed against melanoma antigens were examined by the leukocyte adherence inhibition test. Blocking factors in drained lymph fell to undetectable levels after 6 days' thoracic duct drainage, whereas it took 9 days for serum blocking factors to fall to similar levels. Peripheral blood leukocytes demonstrated cell-mediated immunity against melanoma antigens before and throughout the period of drainage, except for the immediate postoperative period. Within 24 hours of closure of the thoracic duct fistula, serum blocking activity had returned, and 17 days later the patient died.


Consecutive primary carcinomas of the breast. The incidence of consecutive primary carcinoma of the breast in 1489 women was 1 percent per year and remained constant for 20 years. The age of women with bilateral carcinomas was 6 years younger than those who had single tumors. Survival after the second tumor tended to be better in women less than 50 years. Patients who developed metastases had a shorter interval between the first and second tumors than those who remained free from the disease. Prognosis was the same in those with nonsynchronous carcinomas as in those with single tumors, and the incidence of positive nodes was the same in both groups. The prognosis was poorest in those who developed synchronous tumors. Prophylactic postoperative radiotherapy did not affect the incidence of consecutive breast carcinomas and did not alter prognosis. The results stress the importance of observing carefully the remaining breast, especially in younger women.


Sarcoma of soft tissue: clinical and histopathologic parameters and response to treatment. Radical dose radiation therapy alone or combined with limited surgery has been employed in the management of 100 patients with primary (71) and recurrent (29) sarcoma of soft tissue. Results of this experience show that a combination of conservative surgery and radiation therapy, based upon radical dose levels and sophisticated techniques, is effective: only 13 of 100 patients showed local regrowth during a followup of 2-12 years. This may be compared with an expected congruent to 25 recurrences had treatment been radical surgery (wide resection or amputation). For lesions located on the distal extremities (elbow-hand, knee-foot) there were local failures in only 3 of 59 (5 percent). Further, 75 percent of patients treated by the improved techniques utilized in the recent 8 years retained a useful limb which is free of pain or edema. Histopathologic grade is demonstrated to be an important indicator of prognosis of local recurrence and of disease-free survival. Local recurrence rates were 0/23, 9/53, and 4/24 for Grades 1, 2, and 3. Disease-free survival rates were 19/23 (86 percent), 27/53 (51 percent), and 4/24 (17 percent) for Grades 1, 2, and 3, respectively. Invasion of skin appeared to be a sign of poor prognosis; 8 of 9 such patients developed distant metastases.


Vascular reactivity to noradrenaline, potassium chloride, and angiotensin II in the rat perfused mesenteric vasculature preparation, during the development of renal hypertension. The degree of reactivity to noradrenaline of the perfused mesenteric vasculature and the blood pressure of the renal hypertensive rat were correlated. Early (true) supersensitivity was demonstrated for noradrenaline and angiotensin but not for KCl. Later (apparent) hyperreactivity to all three substances was related to an elevated maximal response. The potentiating actions of endogenous angiotensin could cause the early (true) supersensitivity to noradrenaline.


Relationship of intramyocardial oxygen tension and epicardial ST segment changes following acute coronary artery ligation: effects of coronary perfusion pressure. The relationship between the magnitude of epicardial ST-segment elevation and intramyocardial oxygen tension after coronary artery ligation was examined in 11 dogs at various coronary perfusion pressures. The ST map significantly reflected local intramyocardial oxygen tension, and the level of coronary perfusion pressure proved to be an important determinant of both local myocardial oxygen balance and the magnitude of ischaemic injury.


Chronotropic response to acetylcholine injected into the sinus node artery of the isolated atrium of the dog. Injection of a single bolus of acetylcholine into the sinus node artery of the isolated atrium of the dog produces a triphasic response similar to that previously observed after a single stimulus to the  vagus nerves. There is an initial, brief but pronounced, cardiac deceleration followed by a brief, slight acceleration, which is then followed by a more prolonged deceleration which is of lesser magnitude than the initial deceleration. The most likely cause of the intermediate phase of cardiac acceleration is a direct effect of acetylcholine on the pacemaker cells, as it is also with the primary and tertiary phases of cardiac deceleration.


Design and function of a mechanical assembly for recording echocardiograms during upright exercise. It has proved difficult to record satisfactorily echocardiograms during patient motion. This report describes the design and preliminary results obtained with an echo harness with which the transducer can be held stationary or moved rapidly and predictably by remote control. With this apparatus, recordings can be made during tilting, drug intervention, and during bicycle and treadmill exercise.


Effects of hypoxia, cyanide, and ischaemia on myocardial contraction: observations in isolated muscle and intact heart. Using potassium cyanide (KCN) to stimulate hypoxia, the effects of intracoronary injections of KCN were compared with total occlusions of the same vessel. Imparied contraction as measured by segment length gauges was of equally abrupt onset following both interventions. The magnitude of systolic expansion at one minute was more marked following total occlusion than after KCN administration.


Changes in regional coronary blood flow with hypertonic mannitol in conscious dogs. Systemic haemodynamics and regional myocardial blood flow responses to hypertonic mannitol were studied in 10 conscious and 23 anaesthetized dogs. Mannitol infusion significantly increased regional myocardial blood flow in the conscious, intact dogs. Mannitol increased total coronary flow 20% in anasethetized animals compared to 80% in the awake ones. In both groups mannitol exerted a significant positive inotropic effect as evidenced by increases in maximal LV dp/dt and dp/dt/p. These studies have also demonstrated that the intact conscious dog that has not received any sedation has an inner:outer wall left ventricular flow ratio greater than 1-0.


The influence of age and the level of arterial blood pressure on the changes in forearm blood flow resulting from sudden alterations in local vascular transmural pressure. Forearm blood flow was measured by venous occlusion plethysmography in normotensive subjects of various ages and in patients with treated or untreated hypertension. Brief exposure of one forearm to pressures below atmospheric was used to study the transient local changes in arterial inflow which occurred with changes in transmural pressure induced in this way. The increase in initial arterial inflow with such an exposure to suction in a group of young normotensive women was only slightly reduced in two groups of older women. However, a group of subjects with untreated hypertension showed a significantly smaller initial inflow during the suction. There was some indication that adequate treatment of high blood pressure might reverse this effect.


Contractile and electrophysiological responses to progressive digitalis toxicity. Contractile force and intraventricular conduction during progressive ouabain infusion were examined in 15 dogs using a Walton-Brodie strain gauge arch and sequential atrial and bundle of His pacing. This permitted: (1) contractile force determination; (2) overdrive of arrhythmias; (3) maintenance of normal contraction sequences; (4) 'normal' ventricular depolarization; (5) rate control; (6) conduction measurements of the H-V interval (His-Purkinje conduction), QRS (intramyocardial conduction), and H-S interval (total intraventricular conduction). Contractile force increased 21.2 plus or minus 4.3% at the onset of toxicity. After toxicity, there was a significant further increase (P smaller than 0.01) to 50.1  plus or minus 12.4%. However, immediately before ventricular fibrillation, a 43.8 plus or minus 8.2% decrease occurred (P smaller than 0.01). H-V time showed no change (from 30 plus or minus 2.7 to 31.5 plus or minus 2.4 ms) at the onset of toxicity but after toxicity, it lengthened to 40.5 plus or minus 3.1 ms (P smaller than 0.05). QRS did show significant prolongation (69.5% plus or minus 5.3 to 79.5 plus or minus 6.9 ms; P smaller than 0.05) at the onset of toxicity, but this was more marked (79.5 plus or minus 6.9 to 130.5 plus or minus 8.1 ms; Pplus or minus 0.01) after toxicity. H-S time was significantly prolonged (99.5 plus or minus 6.2 to 111.0 plus or minus 8.9 ms) before (P smaller than 0.02) and after (P smaller than 0.01) toxicity (111.0 plus or minus 8.9 to 171.1 plus or minus 10.6 ms). During toxicity there is progressive increase in contractile force with continued ouabain infusion Progressive prolongation of intramyocardial conduction occurs in nontoxic and toxic doses, but His-Purkinje conduction is prolonged only in supratoxic doses.


Site of initial excitation and current threshold as a function of electrode radius in heart muscle. End-diastolic current thresholds have been measured in 13 open chested dogs as a function of electrode radius by stimulating the left ventricle with epicardial disc electrodes ranging in a radius from 0-3 mm to 9 mm. Thresholds for cathodal rectangular short stimuli as well as specifically for cathodal make stimulation, proved to be proportional to the electrode radius to the power 1-5. This relationship between radius and threshold can be explained theoretically, assuming that electrical stimulation results in a propagated depolarization front if a critical current density is reached somewhere in the myocardium. The current distribution measured over the electrode and the site of initial depolarization in the tissue are in accordance with this theoretical explanation.


The organization of the nervous system in the crayfish Procambarus clarkii, with emphasis on the blood-brain interface. Central neural connectives and peripheral nerves of the crayfish Procambarus clarkii are surrounded by an acellular neural lamella, beneath which lies a layer of specialised glia, the perineurium. Cell process of the connective perineurium interdigitate extensively, and are frequently closely associated with each other by gap junctions. Occasional zonulae occludentes are encountered. Nerve perineurium, however, is much less elaborate, and may be reduced to a single or incomplete cell layer. In both connective and nerve, the perineurium appears involved in the formation of the collagen-like fibrils of the neural lamella. The comparative fine structure of connective and peripheral nerve correlates well with recent experimental studies in crayfish, where it was concluded that the perineurium in connective but not nerve offers some restriction to diffusion of small ions and molecules. Within the connective, deeper glia re either closely associated with axons (Schwann cells) or lie relatively free in the extracellular space. Cytoplasmic process of both cell types possess "tubular lattice" systems, which are especially elaborate in the Schwann cells. The extracellular space contains a flocculent material and bundles of collagen, together with layers of basal lamina-like material. The physiological implications of the observations are discussed.


Identification of the vasopressin-neurophysin II and the oxytocin-neurophysin I producing neurons in the bovine hypothalamus. Immuno-enzyme histochemical investigations on the bovine hypothalamus showed that vasopressin and oxytocin are synthetized in separate neurons. Moreover, it was found that the vasopressin-producing neurons are identical with the neruophysin II-producing neurons, while the oxtocin producing neurons correspond with the neurophysin I-producing neurons. From this result it is concluded that, in the species studied, neurophysin I is the carrier protein of oxytocin and that neurophysin II is the carrier protein of vasopressin. The bovine vasopressin-neurophysin II producing neurons and the oxytocin-neurophysin I producing neurons are both present as well in the suparoptic nuclei as in the paraventricular nuclei. In the supraoptic nuclei, the vasopressin-neurophysin II neurons predominate in number; in the paraventricular nuclei, the oxytocin-neurophysin II neurons predominate. The two kinds of bovine neurosecretory neurons are partly localized in separate areas. Moreover, the vasopressin-neurophysin II neurons and the oxytocin-neurophysin I neurons show distinct morphological differences.


Thick filaments in vertebrate smooth muscle. Smooth muscle cells of the mouse vas deferens fixed with 5% glutaraldehyde contained three types of filaments, namely, thin (50-80) A) filaments, intermediate (100 A) filaments and thick (120-180 A) filments. However, in 2 out of 16 experiments, under identical conditions, the cells did not contain thick filaments. With OSO4 fixation, thin filaments were not prominent, the most obvious being thick (120-250 A) and intermediate (100 A) filaments. After soaking in a modified Ringer solution under no applied tension for one hour, thick filaments (120-180 A) appeared prominently in smooth muscle cells of the mouse vas deferens and thin filaments were in ordered bundles. By 4 hours, thick filaments had increased in size and density, with thin filaments distributed randomly around them. After 8 hours in Ringer, thin filaments were diffuse and difficult to discern, while thick filaments were large (up to 300 A) and electron-dense. Intermediate (100 A) filaments were present in association with dark bodies. Physiological experiments indicated that the intracellular components responsible for the development of a mechanical response were still functional at this time. The presence of "thick filaments" is also reported in degenerating smooth muscle cells of the guinea-pig vas deferens in tissue culture.


A study of 14C-proline and 14C-hydroxyproline incorporation in different homogenate fractions of the hepatopancreas of the snail, Helix pomatia L. The fate of 14C in snails given 14C-proline and 14C-hydroxyproline has been examined by radiometric analyses of hepatopancreas homogenates. Free 14C-proline and 14C-hydroxyproline in the structural protein of three different hepatopancreas  homogenate fractions: (a) granules, (b) small calcium spherites, and (c) large calcium sperites. The presence of hydroxyproline in granules and calcium spherites gives reason to believe that a fibrillar protein related to the collagen-type might occur within these structures. The 14C-proline and 14C-hydroxyproline incorporation test measured total radioactivity of each homogenate fraction, expressed as net counts per minute (cpm) per mg of dry weight of each fraction. The radioactivity of the granule and small calcium spherite fractions was about 6-8 times greater than that of the large calcium spherite fraction.


Unusual fine structure of sensory hair triad of the millipede, Polyxenus. Three sensory hairs are inserted at right angles to teach other at the temporal region of the head of Polyxenus. They display structural features characteristic of trichobothria and of scolopidia as well. They also manifest several unusual details: 1) The dendritic cilia are enclosed within a capsule formed by enveloping cells. 2)  The dendritic cilia are interconnected by desmosome-like junctions. 3) The 9 X 2+0 organization of the dendritic ciliary microtubules is maintained over the entire length of the cilia. 4) Neither a tubular body nor even so much as an inflation of the dendritic cilia develop. 5) Pores and pore tubules occur in the lower halves of the hairs. This uncommon combination of structural details renders the modality of the adequate stimulus uncertain. Though most features suggest a mechanoreceptor, the hairs could function as chemo-, hygro- and/or thermoreceptors as well.


The fine structure of the olfactory and vomeronasal organs of a lizard (Tiliqua scincoides scincoides). Olfactory epithelium in Tiliqua scinoides is of a loosely packed pseudostratified type. It receives secretion from the supporting cells and the underlying glands of Bowman. Its surface bears microvilli and cilia from sensory cells and microvilli from supporting cells. The vomeronasal epithelium is also pseudostratified but higher and more closely packed. Its surface carries  microville from sensory and supporting cells but lacks cilia. Vascular connective tissue penetrates it almost to the epithelial surface but is always outlined by basal cell processes and a basal lamina. There are no secretory cells in or under the sensory epithelium but some cells in the epithelium of the mushroom body contain secretion granules. Sensory cells of both epithelia are bipolar neurons. The perikarya of the vomeronasal cells are more neuronal in character. Axonic processes are similar in both, dendrites are distinctive. Olfactory dendrites end in rounded rods bearing microvilli and cilia of an unusual type. Microville with filamentous cores occur on vomeronasal dendrites. There are no cilia, but 2-6  centrioles appear below the cell surface. Basal cells are structurally similar in both epithelia, but axonic processes of olfactory cells are surrounded by supporting cell processes, while vomeronasal axonic processes are surrounded by basal cells before they leave the epithelium. The presence of cilia and microville on the surface of the sensory cells is discussed in relation to the physical conditions surrounding them.


Functional states and fine structure of the contractile apparatus of the penis retractor muscle (PRM) of Helix pomatia L. The ultrastructure of the isolated glycerinated penis retractor muscle (PRM) of Helix pomatia was investigated. The diameter distributions of thick myofilaments from birbre cross sections in the relaxed, phasic contracted, tonic contracted, and in the catch state.s show that a characteristic filament spectrum is formed in the catch state and its preceding active state. The significant structural differences are discussed in relation to earlier hypotheses related to the catch state


Electron microscopic studies on the uptake of exogenous marker particles by different cell types in the guinea pig metaphysis. Guinea pig metaphyseal bone was exposed to horse spleen ferritin in vitro and to colloidal thorium dioxide in vivo. The cellular uptake and intracellular accumulation of these marker particles were studied ultrastructurally. In vitro, the ferritin molecules were found to spread evely throughout the tissue. After 1-2 hours ferritin was mainly found in plasma membrane invaginations and in endocytic vesicles of varying size. At 4-6 hours a successive accumulation of the marker in secondary lysosomes could be observed. In addition to ferritin, the lysosomes and the large endocytic vesicles often contained other inclusions. In vivo, the pattern of intracellular accumulation of the marker particles was identical to that in vitro. Moreover, the presence within the cells of similar amounts of thorium dioxide after 1 and 4 days suggested that these indigestible molecules are stored intracellularly for a considerable time. In accordance therewith there were no definite signs of extrusion of labeled bodies or secretion of the exogenous marker by exocytosis. Ferritin and thorium dioxide were taken up by all cell types in the metaphysis. Both in vitro and in vivo perivascular cells type B ingested large amounts of marker particles, whereas chondroclasts, endothelial cells. perivascular cells type A and osteoblasts showed a more restricted endocytizing ability. On the basis of these observations, the functional significance of different cell types in the resorption of the epiphyseal cartilage and the formation of bone is discussed.


Fine structural and cytochemical observations on lamellar bodies in nerve cells of the medulla oblongata of the rat. Stuctures identified as lamellar bodies have observed in neurons of the dorsal sensory nucleus of the vagus of the rat medulla oblongata. They consist of stacks of parallel, regularly spaced cisternae which either run straight or curve forming a whorl. Finely textured, electron-dense fibrils are present between adjacent cisternae which are devoid of ribosomes. Ribosomes are attached only to the outermost surface of outer cisternae which are often continous with rough endoplasmic reticulum. Cytochemical studies reveal that these intercisternal fibrils contain abundant amino and imidazole groups as well as carboxyl groups. It is suggested that lamelar bodies arise by close alignment of parallel rough surfaced cisternae with subsqent loss of ribosomes from their surface. In addition, it is inferred that polar groups of intercisternal fibrils play an important role in the regular arrangement of cisternal membranes and in the dissociation of ribosomes from cisternae.


Organ culture of adult guinea-pig intestine. III. Mitotic-activity and cellular migration. The mitotic activity and the cellular migration have been studied in explants of adult guinea pig intestine cultured for 24 hours. The mitotic index after a significant increase in the first hours of culture, decreases steadily thereafter. The DNA synthesis persists in the crypts for 24 hours at least and cell migration can be observed. These results demonstrate that organ culture of adult intestine may be used as a model for the study of intestinal function.


Identification of the vasopressin-neurophysin producing neurons of the rat suprachiasmatic nuclei. Immuno-enzyme histochemical investigations on the hypothalamus of the normal rat showed (1) that the suprachiasmatic nuclei produce vasopressin; (2) that it is highly probable that these nuclei do not produce oxytocin. From the present and previous investigations it may be concluded that the suprachiasmatic neurons produce a vasopressin-neurophysin complex.


On the functions of the pore cells in the connective tissue of terrestrial pulmonate molluscs. The fine structure of the pore cells in connective tissue in the kidney of Achatina achatina and the skin of the slug Arion hortensis is described and evidence is presented which shows that these cells, in the latter species, are involved in the synthesis of the respiratory blood pigment, haemocyanin. The involvement of these cells in phagocytosis of colloidal particles, was demonstrated following introduction of ferritin and colloidal gold into the blood. The extracellular coat which surrounds the cells is permeable to ferritin, but is impermeable to colloidal gold. Following penetration of the extracellular coat the ferritin enters the sub-surface cisternae and is taken into the cells where it crystallises within membrane-bound vesicles.


Lymphocyte differentiation and antibody synthesis in the secondary immune response of peroxidase stimulated lymph nodes of rat. Lymphocyte differentiation and specific antibody synthesis were studied in the course of the secondary immune response of horseradish-peroxidase immunized rat popliteal lymph nodes by electron microscopic immunocytochemistry. From primary immunization, mature plasma cells containing specific antibody remained as long as 10 months. Antihorseradish peroxidase antibodies were localized in lymphocytic blast cells on Day 3 after restimulation with antigen. In the subsequent days blast cells were still present, and shifting to mature stages occured. During immunocyte differentiation and maturation vesicles and tubules of the Golgi complex became filled with specific antibody suggesting occasional secretion of antibody via the Golgi apparatus. At very mature cell stages, antibody was accumulated in distended cisternae.


The neurosecretory cells of the optic lobe in Carcinus maenas (L). The six types of neurosecretory cell in the optic lobe of Carcinus maenas described by light microscopy are recognised by electron microscopy. They are categorised according to size, distribution of organelles and type of neurosecretory product. The neuro-secretory material,produced as granules by the Golgi bodies, migrates to the cell periphery eventually reaching the sinus gland via the neurosecretory cell axon extension. No change in size occurs in the granules but the density does alter. Each cell type has its own characteristic type of neurosecretory granule based on size and electron density. Multivesicular and lytic bodies in cell types 1,2,3,4 and 6 suggest a cycle for degrading neurosecretory material. Such a cycle is not so evident in cell type 5. Peripheral release of neurosecretory material is suggested for cell type 6 although the fate of the material is unknown.


The differentiation of the acrosome in the spermatid of the budgerigar (Melopsittacus undulatus). The development of the acrosome of the budgerigar spermatid was studied under the electronmicroscope. The acrosome arises from a granule derived from the Golgi apparatus which interacts with the nucleus to form a cone shaped acrosomal cap and a perforatorium. A quanity of cytoplasm and plasma membrane is captured from the cell periphery and incorporated into the substance of the acrosome. The possible significance of the developmental phases and comparative avian spermatology is discussed.


Distribution and dimension of the T-system in different muscle fiber types in the atlantic hagfish (Myxine glutinosa, L.). Triad density relative to sarcomeres, size of T-system tubules, sarcomere length, muscle fiber diameter in native and fixed states, and size of myofibrils were measured in four straited muscle fiber types in Atlantic hagfishes (Myxine glutinosa, L.) of different sizes. Traids occur at A/I-injunctions in all fiber types. The density of traids relative to sarcomeres is higher in "white" than in "red" muscle fibers. The T-tubules show no sign of branching. The area of the T-system tubules is 3-4 times the surface area in 80 mum "white" muscle fibers and 1-2 times that in 60 mum "red" fibers. The size of myofibrils is similar in "white", "intermediate", and "red" fibers of m. parietalis, and constant through a large span of animal size. In "white" fibers, increase in diameter up to 90 mum is accompanied by an increase in the number of myofibrils, not by an increase in the individual size of the myofibrils. Above 90 mum, "white" fibers grow by increasing the amount of intermyofibrillar space. This is reflected by an extensive shrinkage of the thicker "white" fibers during the preparative procedure for electron microscopy, a shrinkage that is limited only by complete packing of the myofibrils. "Red" fibers shrink much less.


Presence of neurophysin and vasopressin in the hypothalamic magnocellular nuclei of rats homozygous and heterozygous for diabetes insipidus (Brattleboro strain) as revealed by immunoperoxidase history. The 3-layer immunoperoxidase-bridge technique was used to study the distribution of neurophysin and vasopressin in the neurosecretory neurons of rats homozygous and heterozygous for diabetes insipidus (Brattleboro strain). In the homozygous rats there was a marked hypertrophy of the hypothalamic magnocellular structures when stained either for neurosecretory material or neurophysin-like antigens. Neurophysin was present in both the paraventricular (PVN) and supraoptic nuclei (SON) of homozygous and heterozygous animals. Less than half of the cells in the PVN and SON were stained for neurophysin. This observation was less apparent when histochemical stains were used to visualize the distribution of neurosecretory material. Although it is generally considered that the homozygous Brattleboro rat does not synthesize vasopressin, a positive reaction was observed in the PVN and SON when anti-[8-lysine]-vasopressin serum was employed in the immunohistochemical procedure.


Effects of hypoxia on the distribution of calcium in arterial smooth muscle cells of rats and swine. Exposure to hypoxia caused an increase in the hematocrit and right heart weight of experimental rats, but did not affect calcium-45 uptake by pulmonary arterial smooth muscle cells. However, autoradiographic studies showed that hypoxia apparently caused a shift of 45-Ca from primarily extracellular sites in arteries of control rats to intracellular sites in tissues of hypertensive rats. Cytochemical studies of calcium distributions in pulmonary arterial smooth muscle cells support the autoradiographic data and show that in both rats and swine the majority of pyroantimonate granules occur extracellulary in control tissues. In contrast, hypoxic tissues displayed a greatly reduced number of granules in extracellular sites and an increase in the amount of precipitate in intracellular sites. In pulmonary arterial smooth muscle cells from hypoxic rats most of the precipitate was associated with the caveolae intracellulares, while in corresponding cells from hypoxic swine in the majority of the pyroantimonate granules were localized to the sarcoplasmic reticulum. Hypoxia may produce pulmonary hypertension by interfering with the ability of the arterial smooth muscle cells to maintain transmembrane ionic gradients, thus producing an effective increase in cytoplasmic calcium levels. The increased calcium may then activate the contractile apparatus to produce a sustained vasoconstriction


Catecholamine fluorescence in the pituitary of the eel, Anguilla anguilla, with special reference to its variation during background adaptation. In the neuro-intermediate lobe (NIL) of the eel, Anguilla anguilla, a specific formaldehyde-induced fluorescence, indicating a catecholamine (CA) innervation, has been demonstrated in the neural lobe processes. Microspectrofluorimetric analyses and pharmacological treatments indicate noradrenaline or dopamine or both to be responsible for the fluorescence. The fluorescence in the NIL has displayed a definite tendency toward variation during the adaptation to a white and to a black background. The highest amounts of fluorescence were generally found in animals adapted to a black background, especially when adapted for a rather long period, and in animals recently transferred to a white background. The lowest amounts of fluorescence were generally found in animals adapted to a white background. This and the result of injections of CA-depleting drugs suggest that the monoaminergic nerves are active when the animal is on a white background, inhibiting the MSH release directly or indirectly or both, or in co-operation with other factors. Specific green fluorescent structures were also found in other parts of the neural lobe supplying the pars distalis. In some pharmacologically untreated specimens and in animals treated with CA-depleting drugs, the intermedia cells fluoresced. Microspectrofluorimetric analyses indicated that this fluorophore was not a CA.


The structure of the tapetum of the eye of the sheep. The structure of the tapetum of the sheep's eye has been examined by transmission electron microscopy. It consists of regularly arranged layers of collagen fibrils, estimated from the hydroxyproline content to make up about 60 percent of the dry weight of the tissue. There are several hundred of these layers in the whole depth, a majority being oriented in the same direction. The collagen is associated with strands of microfibrillar material as well as with cells of both fibrocyte and smooth muscle types.


An ultrastructural quantitative method for the evaluation of the permeability to horseradish peroxidase of cerebral cortex endothelial cells of the rat. A quantitative method for the evaluation of the importance of pinocytotic phenomena in cerebral cortex capillaries is proposed. The method involved the counting of labeled "caveolae intracellulares" in endothelia cells with the use of horseradish peroxidase as a tracer molecule. A mean pinocytotic value per capillary is then computed. It is demonstrated that the value obtained after irradiation of the brain is higher than in control animals. This information may provide an ultrastructural quantitative approach to the analysis of the blood brain barrier and of other problems related to vascular permeability of the cerebral cortex.


Structure and ultrastructure of the pituitary gland in the sea lamprey, Petromyzon marinus at different stages in its life cycle. The structure and fine structure of the pituitary gland in the sea lamprey, Petromyzon marinus L., are described at all major stages in the life cycle. Synthetically active adenohypophysial cells are evident in even the smallest ammocoetes examined (body length 2.5 cm). An attempt is made to correlate changes in the activity of pituitary cell types with biological events. In the neurohypophysis a single fibre type was discriminated in electron micrographs. This contained electron-dense cytoplasmic granules 800 to 1600 A in diameter.


Ultrastructure of pars nervosa and pars intermedia of the Lamprey, Lampetra tridentata. The pars intermedia of the adult lamprey is separated by perivascular spaces and a capillary plexus from the pars nervosa. No penetration of nerve fibers into the pars intermedia was found. The pars nervosa, which constitutes the posterior wall of the infundibulum, consists of an ependymal layer and a fuchsinophilic fiber layer; the latter contains at least four different types of axonal endings. The pars intermedia is avascular and is composed of a small proportion of non-secretory cells and a large proportion of secretory cells. The secretory granules in the cells of the pars intermedia seem to be discharged toward the capillaries that separate the pars intermedia from the pars nervosa. Although no direct nervous or vascular connections were found between the pars nervosa and pars intermedia, a mechanism of control of secretory activity in the pars intermedia cells by the central nervous system appears likely.


Ultrastructure of nerve plexus in flatworms. II. Sites of synaptic interactions. Synaptic components from the peripheral nervous system of the polyclad flatworm. Notoplana acticola, are described from electron microscopic observations. Quasi-neuropile, defined as clusters of neurites containing synaptic vesicles, occurs as scattered islands among the peripheral nerve cords of the plexus. Some neurite clusters only contain one type of synaptic vesicle but others are mixed. The most usual synaptic configuration consists of a single presynaptic element and a pair of postsynaptic neurites sharing a common synaptic cleft. These synapses are polarized and contain clear, 420 A vesicles. GABA-type synapses are also found. At least two kinds of solid-core vesicles also occur.


Acid phosphatase localization in neurons of Bulla gouldiana (Gastropoda: Opisthobranchia. The organization of the ganglia and the ultrastructure of the neurons of Bulla gouldiana are similar to those described for other molluscs. Acid phosphatase positive reactions were found in the large pigmented granules, small dense bodies, multivesicular bodies, and Golgi lamellae and associated vesicles. The small dense bodies and multivesicular bodies may be stages in the formation of the larger pigmented granules which are interpreted as lysosomes. Comparison is made between the pigmented granules in Bulla and the lipofuscin bodies of vertebrate neurons. The possible involvement of these pigmented granules in the hyperpolarization of Bulla and Aplysia neurons to light is discussed.


The fine structure and innervation of gill lamellae in Anodonta. Gill lamellae of a bivalve Anodonta woodiana lauta (v. Martens) were observed by electron microscopy. The Anodonta gill wall consists of a single layer of epithelial cells, its basal lamina and the underlying connective tissue layer. It was confirmed that there is no true endothelium in the vessels and that the connective tissue layer of the vessel wall is therefore in direct contact with the blood. Cells of a specific type referred to as "trabecular cells" lie in the blood lacunae. These cells closely resemble the pillar cells of fish gills, but show certain fundamental differences. Characteristic features of the trabecular cells are (1) an elongated cell body which lies across the vascular lumen and attaches to the vessel wall by means of the tips of their long processes, (2) two types of myofilaments (thick and thin) in the cytoplasm, (3) external dense plaques at the cell surface which are associated with the insertion of myofilaments into the cell membrane, (4) direct contact between the cell surface and the blood except at the regions where the cell is covered by external plaques and connective tissue fibrils. These facts suggest that the Anodonta trabecular cell is not analogous with the pillar cell of fish gills but rather with muscle cells which show a specific morphological modification and a peculiar relationship to the vessel wall due to the absence of the endothelium. These cells are assumed to regulate blood flow within the gill vessels. As to the permeability of the wall of Anodonta gill vessels, junctional complex consisting of an intermediate and a septate junction between adjacent gill epithelial cells probably plays the main role as a barrier between the blood and the surrounding water. The basal lamina underlying the gill epithelium is assumed to act as a coarse permeability barrier. Numerous nerve endings of unknown function are observed in the gill epitheliu. It is strongly suggested, however, that they are associated with the additional function of the Anodonta gill lamellae as a food-sorting device.


Nerve endings in rat carotid body.

Nerve endings in rat carotid body. The carotid body of the rat consists of "glomera" interspersed by blood vessels and nerve bundles. Each "glomus" consists of 2-12 Type I cells, incompletely invested by 1-3 Type II cells. Type I cells are characterised by the presence of numerous dense cored vesicles in their cytoplasm and may exhibit "synaptic" -like contacts with each other. Small efferent nerve endings make synaptic contact with one or more Type I cells. Large cup-shaped afferent nerve endings make multiple synaptic contacts of two kinds with one or more Type I cells. A second kind of efferent nerve ending is occasionally seen in synaptic contact with one of these afferent nerve endings. A model for the mode of operation of the glomus as a chemoreceptor is proposed.


Pituitary cell activities in gonadectomized rats treated with estrogen. The incorporation of 14C-leucine into LTH and STH, the uptake of 3H-estradiol into the pituitary and the appearance of the LTH and LH cells were studied in male and female rats gonadectomized at the age of 30 days and chronically treated with estradiol (E). The biosynthesis of LTH in the pituitary of ovariectomized rats was decreased 15 and 60 days after the operation to the level of intact males. This decrease is followed by the reduction of the number of immunochemically stained LTH producing cells. Chronical administration of estradiol stimulated the LTH synthesis and maximal incorporation of 14C-leucine was obtained in ovariectomized rats. Maximal relative increase of labeled LTH was noticed in the pituitaries of intact male rats treated with E. STH synthesis is inhibited by treatment with E and maximal decrease was obtained in intact males. The luteinizing LH cells were still hypertrophic in the pituitaries of gonadectomized E treated rats, but the number of castration cells was reduced. On the basis of these results we can conclude that the castration of 30-day-old rats of both sexes does not alter the sex difference in the reaction of LTH and STH cells to estradiol.


Microbodies of the rat renal proximal tubule: ultrastructural and cytochemical investigations. The present study was undertaken to provide a detailed morphological and cytochemical characterization of the microbodies of the rat renal proximal tubule following perfusion fixation. The following observations were made: 1) Two basic types of microbodies (Mb-I and Mb-II) can be identified. Mb-I have both circular and tubular profiles which are located peripherally within the granular matrix of these microbodies. Mb-II have marginal plates and crystalloid inclusion in addition to circular and tubular profiles. 2) Circular and tubular profiles, 100 nm in diameter, described by previous investigators as being infrequent in occurrence, are the most consistent morphological characteristic of rat renal microbodies after perfusion fixation. These profiles have a homogeneous center surrounded by a double or single ring of granules. The uniform size and spacing of these granules within profiles establish a basic 100 A periodicity found in both types of microbodies. 3) Evidence is presented which suggests that both "nucleoids" and "tubular protrusion rods" as described by other investigators of the rat renal microbodies may result from poor fixation and/or osmotic stress. 4) The density of the matrix of Mb-I is, in contrast to previous reports, greater than the density of adjacent mitochondria. 5) Marginal plates or crystalloid inclusions were demonstrated in some microbodies (Mb-II) of all the rats studied; periodicities of 100, 200, and 300 A were identified within these structures. 6) Both types of microbodies were positive for catalase activity, but were negative for acid phosphatase activity. On the basis of both morphological and cytochemical criteria, it seems plausible that these two populations of renal microbodies (Mb-I and Mb-II) represent a morphological and functional continuum.


Ciliated sensory neurons in the lip of the squid Lolliguncula brevis Blainville. The lip of Lolliguncula brevis is a muscular fold covered by a simple columnar epithelium and overlayed medially and distally by a non-cellular cuticle. Bipolar sensory cells in the epithelium have a shallow pocket with cilia and microvilli at the free end of their dendrite. The cilia project out onto the surface through pores in the cuticle. Cells with intracellular cilia were observed below the epithelium. These cells send a process toward the surface of the lip. These two receptors are compared to the receptors previously described from the lip of Sepia.


Ciliated sensory cells and associated neurons in the lip of Octopus joubini Robson. The lip of Octopus joubini is a fleshy fold around the beak that is subdivided distally into finger-like papillae and overlayed by an uninterrupted noncellular cuticle. The muscular core of the lip has a high proportion of nervous tissue. The simple epithelium contains numerous ciliated sensory cells, especially in the papillae. In many of these cells the cilia lie deep within the cytoplasm and usually appear to extend toward the surface. Receptors with intracellular cilia also lie below the epithelium and send dendrites bearing cilia to the surface. Large unipolar interneurons that may receive synapses from the ciliated receptors lie in the musculature near the papillae. The sensory system of the octopus lip is more advanced than that of the squid, and it is very similar to that of Sepia. The relationship of these findings to the phylogeny and ecology of cephalopods is discussed.


Graphic-digitizer analysis of axon spectra in ethmoidal and lingual branches of the trigeminal nerve. Sections were removed from the lingual and ethmoidal nerves of cats and histologically prepared, and the fibers were analyzed under the light microscope. Neural dimensions were measured by a new technique, employing a graphic digitizer and computer. The outline of a neural structure was traced with the digitizer pen, and the total number of axons, their cross-sectional areas, shapes, diameter spectra, and locations within the nerve were calculated. Both nerves had unimodal axon spectra with the peak between 2 and 6 mum diameter. Differences in axon composition occurred over the diameter range of 9 to 20 mum; the lingual nerve had many axons in this range, the ethmoidal nerve only a few. The total number of myelinated axons was near 4000 in the lingual nerve, near 1400 in the ethmoidal nerve; only the latter had many large-sized Remak bundles (containing C-fibers). Most myelinated axons were not perfectly circular but exhibited various degrees of distortion.


On the fine structure of the external glial layer in the isocortex of man. The surface of the external glial layer of the isocortex in the human temporal lobe is generally slightly undulated, with a few protrusions and indentations. The surface is formed by an uninterrupted basement membrane which is continuous over the surface no matter how tortuous it becomes. The overall thickness of the glial layer is generally 15 to 25 mum, but diminishes to about 5 mum immediately beneath blood vessels. It consists mainly of a variable number of stacked glial cell processes. Two groups of cell bodies are encountered particularly in the middle and lower levels of the glial layer. Most of the cells are specialized fibrous astrocytes. They are characterized by eccentrically placed, rounded nuclei with homogeneously dispersed chromatin, and electron-lucent cytoplasm rich in filaments. Lipofuscin pigment granules occupy large areas of the perikaryon. The astroglial cells give rise to four types of processes: foot-processes, tangential and radial processes, and processes irregular in outline. The foot-processes ascend towards the cortical surface and terminate as flat expansions spreading out immediately beneath the basement membrane. Contiguous terminal expansions are connected by gap junctions. The individual profiles are irregular in form and fit together like in a jig-saw puzzle. The plasmalemma beneath the basement membrane is underlined by a fuzzy material, which is penetrated by glial filaments. In the terminal expansions individual or groups of mitochondria are abundant. The tangential processes are straight and slender and form a lattice within the middle and deep level of the external glial layer. They contain numerous filaments, evenly distributed or fasciculated. The remainder of the lattice is filled up by a considerable number of processes irregular in outline and varying greatly in size. They contain fewer filaments than the tangential processes, coursing in all directions, and glycogen particles. In both types of processes only a few mitochondria are present. These processes are also connected by gap junctions and desmosomes, too. Large cytoplasmic areas of astroglial cells localized in the deepest portion of the glial layer protrude into the neuropil of the molecular layer, giving rise to several radiate processes, which extend deeper into the cortex. The second, heterogeneous group of cell bodies is characterized by elongated nuclei, ovoid or irregular in outline, which are smaller than those of astroglial cells, and contain blocks of condensed chromatin; a thin cytoplasmic rim generating a few appendages surrounds the nucleus. The first sub-type is characterized by a nucleus with large chromatin blocks bordering the inner nuclear membrane and a medium-dense cytoplasmic matrix. The second sub-type displays smaller chromatin condensations at the inner nuclear membrane and many microtubules are scattered throughout an electron-lucent cytoplasm.


The postnatal development of the sexually dimorphic duct system and of amylase activity in the submandibular glands of mice. The submandibular glands of developing and mature Strong A mice were studied by light and electron microscopy. The glands of both sexes show the same cell types during development, but during maturation the glands display a degree of sex-dimorphism. Striated ducts, which differentiate from the larger intralobular ducts present in the neonatal gland, first appear by 5 days of age and reach their mature condition by 20 days of age. Granular convoluted tubule cells, which differentiate from striated duct cells, are first seen at 15 days of age in both sexes. Subsequently, they show a more rapid development in males than in females, and are dimorphically represented by 20 days of age. Intercalated ducts in the neonatal gland contain nongranular and granular cells. With maturation the number of granular cells decreases, apparently due to their conversion into the nongranular type, with their eventual disappearance from the glands of adult males. Their retention in adult females further defines the sexual dimorphism shown by these glands. Amylase activity in gland homogenates is first detectable at 20 days of age in both sexes. During development the male glands show a rapid rise in levels of amylase activity, whereas female glands show a more gradual rise. In mature animals, male glands have higher levels of amylase activity than female glands. The developmental and adult status of amylase activity parallels that of the granular convoluted tubules.


The size of fibroin messenger RNA and its polyadenylic acid content. The molecular weight of fibroin messenger RNA has been measured by its contour length in the electron microscope and its electrophoretic mobility under conditions of complete denaturation. These methods give values of 5.6 times 10-6 and 6.0 times 10-6 daltons, respectively. The average molecular weight of 5.8 times 10-6 (1.6 times 10-4 base residues) would be expected to code for a protein of 414,000 daltons, a value about 12 percent larger than the most recently published size for fibroin. When the mRNA is prepared carefully to avoid shear breakage, it is as homogeneous in size as ribosomal RNA. Between 43 percent and 81 percent of the mRNA molecules bind to oligo(dT)-cellulose and are presumed to contain a poly(A) sequence. This sequence, isolated after ribonuclease digestion, comprises about 0.6 percent of the molecule, or an estimated 100 nucleotides. The poly(A) has been localized at the end of the molecule by hybridizing with a small poly (dT:dA) piece and subsequent visualization by electron microscopy. This observation, along with the ability of reverse transcriptase to transcribe fibroin mRNA with an oligo(dT) primer, demonstrates that the poly(A) is at the 3' end of the mRNA.


Structural genes adjacent to interspersed repetitive DNA sequences. The observation that repetitive and single copy sequences are interspersed in animal DNAs has suggested that repetitive sequences are adjacent to single copy structural gene sequences. To test this concept, single copy DNA sequences contiguous to interspersed repetitive sequences were prepared from sea urchin DNA by hydroxyapatite fractionation (repeat-contiguous DNA fraction). These single copy sequences included about one third of the total nonrepetitive sequence in the genome as determined by the amounts recovered during the hydroxyapatite fractionation and by reassociation kinetics. 3H-labeled mRNA from sea urchin gastrula was prepared by puromycin release from polysomes and used in DNA-driven hybridization reactions. The kinetics of mRNA hybridization reactions with excess whole DNA were carefully measured, and the rate of hybridization was found to be 3-5 times slower than the corresponding single copy DNA driver reassociation rate. The mRNA hybridized with excess repeat-contiguous DNA with similar kinetics relative to the driver DNA. At completion 80 percent of that mRNA hybridizable with whole DNA (approximately 65 percent) had reacted with the repeat-contiguous DNA fraction (50 percent). This result shows that 80-100 percent of the mRNA molecules present in sea urchin embryos are transcribed from single copy DNA sequences adjacent to interspersed repetitive sequences in the genome.


Individual histone messenger RNAs: identification by template activity. Newly synthesized polysomal messenger RNAs from cleavage stage embryos of the sea urchin Arbacia punctulata and Lytechinus pictus that contain putative histone mRNAs have been fractionated on 6% polyacrylamide slab gels. At least 8 RNA species with unique electrophoretic mobilities have been recognized. The complex of RNAs has been eluted from the gels in three groups, A, B, and C, in increasing order of mobility. The template activity of the three fractions and the unfractionated starting material was examined in the mouse Krebs II ascites tumor cell-free protein synthesizing system. The unfractionated messenger complex programs the synthesis of proteins that co-electrophorese exclusively with sea urchin histones in both sodium dodecyl sulfate and acid urea gel systems. The products of in vitro protein systhesis stimulated by the individual polyacrylamide gel RNA fractions were similarly examined. Each stimulated protein synthesis and was enriched for specific histone templates. We conclude that RNA fraction A is template for histone f1, C is template for histone f2a1, and B serves as template for f2b, f2a2, and f3 histones. A minor degree of contamination of the A and B RNA fractions was obvious from the production of other histones by each template. The co-electrophoresis of specific template activity with specific radiolabeled RNAs supports the concept that most or all of the labeled RNAs are indeed themselves the histone mRNAs.


Abrin and hurin: two new lymphocyte mitogens. Two plant proteins, abrin from the seed of Abrus precatorius and hurin from the seed of Hura crepitans, are potent lymphocyte mitogens. The extent of stimulation of BALB/C AND CBA strain mouse spleens by these factors is significantly greater than that attained with PHA or PWM and requires thymus-derived lymphocytes. Abrin has been purified to electrophoretic homogeneity, physically characterized, and may undergo conversion from a toxic to mitogenic form. Hurin is the best mitogen we have tested.


Effects of cycloheximide on the "autocatalytic" nature of the maturation promoting factor (MPF) in oocytes of Xenopus laevis. It is shown that a factor arising during the course of maturation in amphibian oocytes is by itself capable of inducing maturation when injected into recipient oocytes even after a series of 10 transfers. The mechanism of action of this phenomenon is shown to be under translational control. Experiments using cycloheximide suggest that MPF does not need protein synthesis for germinal vesicle breakdown (GVBD), but does require a translational step when serially transferred in order to sustain its renewal ("autocatalytic") capacity. It is further shown that oocytes of Xenopus laevis lend themselves to an in vitro system, since when matured under the action of some steroids (progesterone or hydrocortisone), they are capable of supporting functional maturation with cleavage and development after having received a transplanted blastula nucleus.


Electron microscopic and biochemical evidence that chromatin structure is a repeating unit. Electron microscopic and biochemical studies demonstrate that the fundamental structure of chromatin depleted of lysine-rich histones is composed of a flexible chain of spherical particles (nucleosomes), about 125 A in diameter, connected by DNA filaments. Such a chromatin preparation can be separated by centrifugation into two fractions which differ in the spacing of the nucleosomes; In one fraction almost all of the DNA is condensed in nucleosomes, while the other fraction contains long stretches of free DNA connecting regions where the nucleosomes are closely packed. The isolated nucleosomes contain about 200 base pairs of DNA and the four histones F2alpha1, F2alpha2, and F2b, and F3 in an overall histone/DNA ratio of 0.97; In such a structure the DNA is compacted slightly more than five times from its extended length; The same basic structure can be visualized in chromatin spilling out of lysed nuclei. However, in this latter case the nucleosomes are very closely packed, suggesting that histone F1 is involved in the superpacking of DNA in chromosomes and nuclei. The chromatin fiber appears to be a self-assembling structure, since the nucleosomal arrangement can be reconstituted in vitro from DNA and the four histones F2alpha1, F2alpha2, F2b and F3 only, irrespective of their cellular origin.


Analysis of drosophila mRNA by in situ hybridization: sequences transcribed in normal and heat shocked cultured cells. Messenger RNA transcribed in cultured Drosophila cells adapted for growth under conditions permitting labeling to high specific acitivty has been analyzed by the technique of in situ hybridization. Poly(A)-containing cytoplasmic RNA binds specifically and reproducibly to about 50 bands in the salivary gland polytene chromosomes. In addition heavy labeling of the beta-heterochromatin associated with each of the chromosome arms is observed. The species which are detected probably belong to the more abundant classes of RNA. When the cultured Drosophila cells are subjected to heat shock immediately before labeling with 3H-uridine, there is a drastic alteration in the pattern of gene transcription detected by in situ hybridization. Most of the mRNA synthesis which could be detected in the normal cell is shut off. Newly synthesized RNA hybridizes strongly to seven new sites which do not bind mRNA from control cells. The new loci correspond almost exactly to the regions of Drosophila polytene chromosomes which puff when intact larvae are subjected to an identical heat treatment.


The action of arachidonic acid on experimental hypertension in the rat. Keeping in mind the vasodilator action of prostaglandins, the control that they exercise over the vascular supply of kidneys and the sympathetic activity, research was conducted in order to establish the effect of arachidonic acid, the precursor of PGE2, on experimental hypertension in the rat. The experimental hypertension was induced by unilateral nephrectomy, followed by the administration of DOCA and the elevated sodium diet. The treatment was short in one group, long in the other, and both groups were compared to a control hypertensive group which received no treatment at all. Arachidonic acid worsened the experimental hypertension by 37% in the long treatment, and by 25% in the short treatment. The administration of lysine-acetylsalicylate diminished this hypertension. A non-saturated acid, oleic acid, which is not involved in prostaglandin synthesis, has no action. The authors would like to emphasize that in one of the previous experiments, L-tyrosine, the precursor of catecholamines, diminished the experimental hypertension in the rat, and also that L-DOPA and IMAO (MAOI) have comparable effects. It seems, therefore, that the depression of the central catecholaminergic activity, which is supposed to be the action of arachidonic acid via an increase in the PGE2 synthesis, appears to increase hypertension. It is noteworthy that the medial forebrain bundle (MFB) is catecholaminergic and that the periventricular system (PVS) is cholinergic. Thus hypertension may represent the peripheral vascular response to anguish which results from the activation of PVS and from the depression of MFB.


Induced synthesis of metallothionein by pig kidney cells in vitro in response to cadmium. Cells of a line (K7), derived from the cortex of the adult pig kidney, synthesize and accumulate high levels of metallothionein when grown in vitro in the presence of low concentrations (0.5 mug/ml) of Cd2+. This indicates that the accumulation of this protein in the kidneys of animals exposed to cadmium is due at least partly to synthesis in situ, and not solely to uptake by the renal cells of metallothionein produced by the liver. It is suggested that the ability to synthesize large amounts of metallothionein indicates the tubular origin of the cells of this line.


Urinary enzymes and kidney damage by aspirin and phenacetin. Two groups of rats were given aspirin and phenacetin in their food at daily doses similar to those taken by humans suffering from analgesic abuse. Both drugs damaged the kidney proximal tubules although phenacetin affected the kidney more severely than aspirin. At the start of the experiment aspirin increased the urinary excretion of lactate dehydrogenase (LDH) while phenacetin raised the excretion of all four enzymes studies (acid phosphatase, alkaline phosphatase, glutamate dehydrogenase (GDH), LDH indicating generalised cellular injury. Subsequent samples of urine collected from rats up to seven weeks showed normal urinary enzyme levels. The value of urinary enzyme measurements in detecting renal damage by drugs is discussed.


Alterations in hepatic drug metabolism and lipid peroxidation during administration of Baygon, a pesticide. Biochemical studies during low- and high-dose administration of Baygon (a pesticide) to young male rats were performed. It was observed that the activities of drug-metabolizing enzymes were decreased even at a low dose of Baygon and the decrease was much more significant during high-dose injections. Lipid peroxidation was increased with a low dose and the increase was much more pronounced with a high dose. Besides these changes the animals showed physical changes such as salivation, fasciculations, etc. The presence of conjugated diene absorption patterns and malonaldehyde formation indicated the in vivo lipid peroxidation dut to Baygon administration. Toxic effects leading to death were noted when the animals were injected with a high dose of the pesticide, Baygon above 25 mg/kg.


A model of lateral diffusion in phosphatide bilayers and natural membranes. Lateral diffusion of phosphatide molecules in liquid crystalline bilayers has been analysed as a case of co-operative lattice diffusion. The potential energy of interaction between two molecules is assumed to arise from Van der Waals interactions of the hydrocarbon chains, and to have the form suggested by Salem [6]. From the observed values of the self-diffusion constant (of the order of 10-8 cm2sec-1) the depth of the potential "well" for two molecules at the equilibrium separation was estimated to have a lower limit of 1.95 kcal per mole, and the energy barrier to lateral motion was estimated to have an upper limit of 7.21 kcal per mole.


Lipids in plant tissue cultures. IV. The characteristic patterns of lipid classes in callus cultures and suspension cultures. Lipids from callus cultures and suspension cultures of higher plants constitute 5 to 8% of the dry tissue's weight. The predominant lipid classes are the sterols, steryl esters, steryl glycosides and esterified steryl glycosides. Considerable amounts of a variety of sterylglycolipids, whose structures are not completely elucidated, are also present. Triglycerides and phospholipids occur in small proportions, whereas monogalactosyl diglycerides, digalactosyl diglycerides and sulfoquinovosyl diglycerides are present only in traces, if at all. Beta-Sitosterol is the predominant constituent sterol, stigmasterol and campesterol as well as a variety of as yet unidentified sterols occur in smaller proportions. The major constituent fatty acids are palmitic, oleic, linoleic and linolenic acids. Saturated very long-chain fatty acids are found in smaller proportions. Unusual fatty acids, such as epoxy acids, which occur in the seed lipids of certain plants, are not found in tissue cultures derived from these plants. Clucose and traces of galactose are the only sugars obtained by acid hydrolysis of the glycolipids occurring in plant tissue cultures.


Calorimetric and freeze-etch study of the influence of Mg2+ on the thermotropic behaviour of phosphatidylglycerol. In the presence of Mg2+ ions phosphatidylglycerol shows supercooling which leads to the formation of a metastable gel phase. This contrasts with the behaviour of this negatively charged phospholipid in the presence of Ca2+ ions (Biochim. Biophys. Acta 39. (1974)432)9 It is demonstrated that the heat content of this phospholipid is dependent on the ionic environment.


Intimal ultrastructure of human umbilical arteries. Observations on arteries from newborn children of smoking and nonsmoking mothers. The umbilical artery was chosen as a possible model for evaluating the vascular injury provoked by tobacco smoking in humans. Cords from newborn children delivered by 15 nonsmoking and 13 smoking mothers were studied in the transmission and the scanning electron microscope. Pronounced intimal changes were seen in the arteries from smoking mothers; the most important findings were degenerative changes of the endothelium such as swelling, blebbing, contraction, and subsequent opening of the endothelial junctions with formation of subendothelial edema. Other observations included dilation of the endoplasmic reticulum in the endothelium and reparative changes such as a considerable widening of the basement membrane. Since similar changes can be induced in arteries of animals by exposure to carbon monoxide or perfusion with nicotine, we conclude that the present study supports the concept that tobacco smoking is harmful to the vascular endothelium. This study also contributes to an understanding of the mechanism through which vascular injury is provoked in heavy smokers.


Hypertension, transmural pressure, and vascular smooth muscle response in rats. The effect of transmural pressure on the responsiveness of vascular smooth muscle was studied using rats with chronic occlusion of one external iliac artery. The arterial pressure in the occluded leg was reduced to approximately half of that in the contralateral unoccluded leg. Helical strips from the low- and high-pressure femoral arteries of spontaneously hypertensive rats and rats with deoxycorticosterone acetate-induced (DOCA) hypertension were compared with corresponding tissues from normotensive controls. The sensitivity of both low- and high-pressure artery strips from the spontaneously hypertensive rat was greater than that of controls when strontium or lanthanum was used as the agonist. The sensitivity of strips from both low- and high-pressure arteries from the DOCA-hypertensive rat was greater than that of controls when potassium, epinephrine, or calcium was the agonist. There was no difference in sensitivity between strips from the low- and high-pressure arteries in any group of rats. Maximum contractile force (contractility) was reduced in femoral artery strips from both legs of all hypertensive rats. The KCl-induced contraction of vascular smooth muscle from both femoral arteries of either form of hypertensive rat was not as readily depressed by high calcium concentrations as was that from the normotensive rat. Changes in sensitivity and contractility associated with hypertension could not be reversed by lowering blood pressure in one leg of a spontaneously hypertensive rat or prevented by protecting one leg from high pressure prior to the induction of DOCA hypertension. The altered sensitivity and contractility of arterial strips in these models of hypertension are not, then, secondary to the increase in wall stress.


Local cerebral blood volume determined by three-dimensional reconstruction of radionuclide scan data. We developed a method to determine in man absolute values of local cerebral blood volume (LCBV) localized throughout the brain in three dimensions and presented in a cross-sectional picture format. Previously, absolute values of LCBV have been determined in vivo by stimulated X-ray fluorescence, but these determinations have been limited to one point in the brain at a time. All other previous estimates of LCBV by external emission counting have been contaminated by the significant contribution of blood in the overlying scalp and cranium. In our method, a transverse section scan is made after the injection of -99m-Tc-labeled red blood cells into a peripheral vein. Data processing then gives a point-to-point estimate of absolute radionuclide concentration analogous to an autoradiograph. After the concentration of blood activity is determined, counting data are converted to a two-dimensional map of LCBV representing a cross section at a known level of the brain. In a series of five baboons, the following equation was obtained for the regression plane that relates LCBV in the center of the brain to arterial carbon dioxide tension (P-ALPHA-CO2) and mean arterial blood pressure (MABP): LCBV equals 2.88 + 0.049P-ALPHA-CO2 MINUS 0.013MABP. In patients, LCBE values ranged from 2 to 4 ml/100 g depending on location; higher values corresponded to regions of cerebral cortex. Differences in blood volumes of focal brain lesions were also quantified.


Effect of sympathetic nerve stimulation on cerebral and cephalic blood flow in dogs. The effect of sympathetic stimulation (stellate ganglion) on dog cerebral and cephalic blood flows was studied via a cervical or a thoracic approach to the stellate ganglion under sodium pentobarbital or chloralose anesthesia. Two different stimulation voltages (3v and 5v) of monophasic pulses were applied for 1 minute. Venous outflow was measured at the confluence of the sagittal, straight and lateral sinuses with the lateral sinuses occluded and with them patent. When the lateral sinuses were occluded, stellate ganglion stimulation resulted in a marked decrease in common carotid blood flow to 38 plus or minus 2.5% (SE) of control and dilation of the ipsilateral pupil, but cerebral blood flow did not change. Similar effects were observed with each of the anatomic approaches, anesthetics, and voltages used and in dogs with low cerebral vascular tone induced by hypercapnia. When the lateral sinuses were kept patent, sympathetic nerve stimulation decreased the venous outflow to 89 plus or minus 2.9% of control and clamping both of the external jugular veins increased venous outflow to 120 plus or minus 2.7% of control. When the lateral sinuses were kept patent and the extracranial venous pressure was increased by clamping both of the external jugular veins, the decrease in venous outflow in response to sympathetic stimulation was even larger: venous outflow was only 65 plus or minus 4.9% of control. We conclude that stimulation of the stellate ganglion has no effect on the cerebral vasculature. Sympathetic stimulation significantly decreases venous blood flow measured at the confluence of the sinuses only when communications between the intracranial and extracranial venous vasculatures are present.


Inherited depression of arterial lipoamide dehydrogenase activity associated with susceptibility to atherosclerosis in pigeons. The activity of lipoamide dehydorgenase (E.C.1.6.4.3) was measured in arterial homogenates from very young pigeons (5-8 weeks old) known to differ in their susceptibility to atherosclerosis. The activity of the arterial enzyme was significantly lower in the atherosclerosis-susceptible White Carneau pigeons than it was in the atherosclerosis-resistant Show Racer pigeons. Lipoamide dehydrogenase is a component of the pyruvate dehydrogenase and alpha-ketoglutarate multienzyme complexes. The first complex catalyzes the conversion of pyruvate to oxaloacetate via acetyl-CoA, and this reaction represents a crucial link between glycolysis and the Krebs cycle. The second complex is essential for the oxidative breakdown of carbohydrates, fats, and amino acids via the Krebs cycle. Reduced activity of these complexes, resulting from low activity of lipoamide dehydrogenase, favors reduction of pyruvate to lactate and a shift to glycolysis. This situation is in accord with other results obtained in avian and human arteries which appear to indicate a higher rate of glycolysis in atherosclerosis-susceptible and atherosclerotic arteries. It appears that the increased dependence of the White Carneau arteries on glycolysis, suggested by the reduced lipoamide dehydrogenase activity, facilitates the development of atherosclerosis in this pigeon strain.


Histamine potentiation of nerve- and drug-induced responses of a rabbit cerebral artery. Rabbit basilar artery rings are normally relatively unresponsive to transmural stimulation of their sympathetic nerve supply. However, in the presence of histamine (0.55 muM), contractile responses to nerve stimulation were markedly increased. Norepinephrine and serotonin concentrations that produce 50% of a maximum contractile response (ED50) were considerably decreased in the presence of histamine; maximum responses to both norepinephrine and serotonin were increased. Although a prejunctional effecto of histamine has not been eliminated, potentiation of responses to transmural nerve stimulation is probably due to an increase in smooth muscle responsiveness to norepinephrine. In rabbit saphenous artery rings, histamine produced a qualitatively similar potentiation of responses to nerve stimulation, norepinephrine, and serotonin except that maximum responses were not increased. Serotonin (0.084 muM) did nog potentiate contractile responses of the basilar artery to transmural nerve stimulation or norepinephrine. Since histamine and serotonin are released from rabbit platelets in response to tissue injury the synergistic effect of these agents on vascular smooth muscle contraction might be advantageous in minimizing hemorrhage. But such a response could also be deleterious if the effects of these vasoconstrictors were prolonged.


Simulation of action potential propagation in an inhomogeneous sheet of coupled excitable cells. Cable theory and active equivalent circuits have been used to simulate the propagation of action potentials along a single nerve or muscle fiber by representing the cell as a unidimensional cable composed of isopotential segments. We extended this method to a two-dimensional sheet of cells which in many ways represents the atrium. Our method consisted of solving for the potential profile of a sheet composed of a large number of isopotential membrane patches, each of which was represented by an active equivalent circuit in which the ionic conductances were functions of voltage and time. The patches were arranged in a rectangular array with resistive interconnections that could be varied over the sheet. We used this model to study the effect of various inhomogeneities on conduction velocity and the resulting wave fronts in a sheet of excitable tissue. Some of these inhomogeneities included different effective internal resistances in the x and y directions, preferential pathways, and discrete regions of changing resistive connections. The results showed that very localized changes in membrane properties or cellular interconnections produce changes in the wave front over broad areas. This model provides a method for computing the wave fronts of action potential propagation in any two-dimensional inhomogeneous sheet of coupled excitable cells.


Correlation between the response of the heart to sympathetic stimulation and the release of endogenous catecholamines into the coronary sinus of the dog. The relationship between the increase in catecholamine levels of the coronary sinus blood and the amplitude of various cardiac responses to adrenergic nerve stimulation was studied in anesthetized dogs. Plasma catecholamine levels in both coronary sinus and aortic blood were measured by a modification of the radiometric enzymatic assay for tissue catecholamines and were found to be 0.622 plus or minus 0.104 (SE) ng/ml and 0.933 plus or minus 0.116 ng/ml, respectively, under basal conditions. The catecholamine levels in coronary sinus blood increased linearly during right cardioaccelerator nerve stimulation up to a frequency of 10 Hz. At this frequency, maximum values were observed in both coronary sinus blood catecholamine levels and cardiac responses. The correlation between the response in heart rate, mean coronary blood flow, and dP/dt of left ventricular pressure and the increase in endogenous catecholamine levels of coronary sinus blood was significant, but the relationship was nonlinear. The present experimental design may prove to be a reliable means of studying the role of the sympathetic nervous system in the regulation of cardiovascular function in vivo.


Wolff-Parkinson-White syndrome. The problem, evaluation, and surgical correction. Physiological studies of the type we have described, when performed in patients with the WPW syndrome, can yield diagnostic information regarding the mechanism of arrhythmia, demonstrate functional properties of therapeutic import, facilitate therapeutic decision-making about drug regimens and presumptively localize the site of pre-excitation as a basis for possible surgical intervention. Based on our experience, we feel that in selected patients, surgical correction of the WPW syndrome is entirely feasible, and can be accomplished in the majority of patients in whom free wall A-V connections are present. The continuing challenge of identification and correction of septal accessory pathways directs our present work with the WPW syndrome.