Hydronephrosis in the mouse: the effects of the short-ear gene, sex and ureteral vascular system.

The short-ear gene in the mouse, se, affects a number of soft tissues; skeletal effects result in reduced body cavities. A high incidence of hydronephrosis in short-ear genotypes has been ascribed to pressure on the lower ureter resulting from crowding of organs in the body cavity. This study concerns the ureteral vascular system as observed in 861 autopsies of mice of varying age, of the three short-ear genotypes, drawn from ten stocks. Incidence and expression of hydronephrosis is greater in short-ear males than in females, and the ratio between the two varies from one stock to another. This study seeks an explanation. Short-ear genotypes have an abnormally high incidence of unusual ureteral veins, hydronephrosis being strongly associated with the more posterior ones. Ureteraonadal and iliac veins. The spermatic vein's more posterior position, compared with the ovarian, is strongly correlated with the sex difference in posterior ureteral venation and thus with the sex difference in incidence of hydronephrosis. Stocks are compared according to the amount of selection for fitness of short-ear genotypes; there is a reduced incidence of hydronephrosis with selection, accompanied by fewer posterior ureteral veins. Age also affects hydronephrosis; its expression increases slightly with age, and the male sese progeny of young mothers appear to be particularly prone to hydronephrosis. Three skeletal mutants segregate; of these fidget, fi, causes a type of hydronephrosis differing somewhat from that caused by se.


Fine structure of satellite cells in growing skeletal muscle.

The morphology of satellite cells was investigated in skeletal muscle from mice of various ages between 7 days and 50 weeks. Satellite cells of very young muscle had abundant cytoplasm which was rich in organelles. Free ribosomes were abundant and usually arranged into polysomes of 5-6 units. Cisternae of rough endoplasmic reticulum were heavily studded with ribosomes and occupied the polar regions of the cytoplasm. Marked dilations of the cisternae, filled with an amorphous electron-lucent material, were a frequent and characteristic feature of satellite cells of very young muscle. The cytoplasm of young cells also contained a well developed Golgi apparatus as well as numerous mitochondria, microfilaments and microtubules. With increasing age there was a rapid reduction in organelles both qualitatively and quantitatively. For rxample, as the number of ribosomes decreased, their organization into polysomes was lost. The rough endoplasmic reticulum was present in cells of older muscle merely as small isolated profiles that lacked dilations. These and other features demonstrated during this study are consistent with the concept that satellite cells are metabolically very active in young muscle but rapidly become quiescent as the animal grows older.


Osteoligamentous guidance of the movements of the human thumb.

On examination of the thumbs of 20 dissected preparations of ligaments and joints, of ten dry skeletons and of a number of living hands, apoposition (from apo = away from) was distinguished as a position in which the first carpometacarpal joint is fully abducted and laterally rotated and in which one or both distal joints of the thumb are flexed. Apoposition is commonly used in writing and it has a specific osteoligamentous basis for its stability: (1) a Y-shaped intermetacarpal ligament is attached by two crura to the base of the second metacarpal bone and by a common stem to the first metacarpal. Together with the palmar and dorsal oblique ligaments it becomes taut at abduction and establishes thereby a fixed center for the circumduction. Stability is enhanced as the circumduction takes place in the radial flat part of the joint away from the center; (2) of the two palmar prominences of the head of the first metacarpal bone the radial is the larger. At 25-30 degrees flexion in the metacarpophalangeal joint the prominence fits into an excavation on the base of the proximal phalanx in a manner which together with the ulnar collateral ligament locks the joint against mutual abduction and lateral rotation, and (3) the radial part of the trochlea of the interphalangeal joint is larger than the ulnar and secures, together with the ulnar collateral ligament, the joint against a radial luxation. Apoposition does not require activity of the thumb muscles; it is brought about by applying an external force to the ulnar side of the thumb and it is checked by ligaments and the shape of the joints.


The autonomic innervation of the interstitial gland of the rat ovary during pregnancy.

The autonomic innervation of the interstitial gland of the rat ovary was studied on days 4, 6, 10, 14 and 18 of pregnancy with the acetylcholinesterase procedure, the Falck-Hillarp technique and electron microscopy after 5-hydroxydopamine treatment. Acetylcholinesterase-positive nerves were present as perivascular plexuses at all stages studied. Adrenergic nerves were present in the interstitial gland in all stages studied. The number and intensity of interstitial fluorescent adrenergic nerves increased as pregnancy progressed. Measurement of norepinephrine with the fluorometric procedure showed a highly significant (p less than 0.05) increase in the neurotransmitter in the ovary on days 14 and 18 as compared to day 4. Fine-structural studies after administration of the false transmitter, 5-hydroxydopamine, showed that the innervation of the steroidogenic cells of the interstitial gland is adrenergic.


The effects of 5-bromodeoxyuridine and isoproterenol on the postnatal differentiation of rat submandibular gland.

The effects of 5-bromodeoxyuridine (BrdU) on the postnatal differentiation of rat submandibular gland and on the isoproterenol-induced changes of differentiation were studied. The rats were injected with BrdU for three consecutive days, beginning at two days of age. The total dose of BrdU was 0.9 mg/g body weight. BrdU caused a severe retardation of growth up to 15 days of age. A rapid growth of the animals between 15 and 22 days indicated a recovery from the effect of BrdU. The growth of the submandibular gland was retarded similarly with a corresponding decrease in DNA, RNA and protein content. Incorporation of tritiated thymidine into the submandibular gland was not altered in the BrdU-treated animals at one and three days after the last injection of the analog. At days 15 and 22 the rate of thymidine incorporation was greater in the submandibular gland of BrdU-treated rats as compared to littermate controls. Isoproterenol stimulated thymidine incorporation into the submandibular glands of two-week-old rats. This stimulation was not observed in rats which received BrdU at age 7-9 days, prior to the administration of isoproterenol. Election microscopic observations, including a quantitative analysis of the frequency distribution of the various cell types in the terminal tubules and developing acini, indicated a retardation of acinar cell differentiation in the glands of BrdU-treated rats. In addition, there was an increase in the number and size of the secretory granules in the terminal tubule cells. BrdU treatment, however, caused no obvious pathologic alterations in the submandibular gland. Administration of isoproterenol for five days, beginning at five days of age, caused an apparent acceleration of the differentiation of acinar cells. In the glands of isoproterenol-treated rats the acinar cells were enlarged and were filled with homogeneous secretory granules. Pretreatment with BrdU partially inhibited the effects of isoproterenol on differentiation and hypertrophy of the submandibular gland. With the given dose of BrdU, approximately 5% of thymine was replaced by bromouracil in the DNA of the submandibular gland. Such a replacement would be consistent with a direct effect of BrdU on the cytodifferentiation in the submandibular gland. However, because of the severe retardation of growth of the BrdU-treated rats, indirect effects can not be excluded.


The systemic arterial pattern of the guinea pig: the pelvis and pelvic limb.

The systemic arterial pattern of 59 guinea pigs was examined by dissection, angiography, or corrosion casting. The blood supply to the pelvis and the pelvic limbs arises as two terminal branches of the aorta, the right and left common iliac arteries, and each of these divides into external and internal iliac arteries. Their pattern of distribution resembles a typical mammalian pattern. The external iliac artery passes throught the body wall to supply the pelvic limb and the internal iliac artery is distributed primarily to the pelvic region and its viscera.


Light and electron microscopic localization of acetylcholinesterase activity in the rat renal nerves.

Acetylcholinesterase activity is shown in the renal nerves of the rat with the technique of Karnovsky and Roots. By light microscopy, the acetylcholinesterase-positive nerves are seen in association with blood vessels, including the glomerular arterioles, and occasionally with renal tubules. By electron microscopy the precipitate appears extracellularly around axons and varicosities. DFP inhibits the deposition of precipitate. Previous demonstration by serial section electron microscopy in the rat revealed that all nerves around the glomerular arterioles contain small dense-cored vesicles characteristic of adrenergic nerves, indicating that the acetylcholinesterase-positive nerves demonstrated here are likely to be adrenergic nerves containing acetylcholinesterase.


Melatonin induction of testicular recrudescence in hamsters and its subsequent inhibitory action on the antigonadotrophic influence of darkness on the pituitary-gonadal axis.

Exposure of adult male hamsters to light-dark (LD) cycles of 0:24 (in hours) for 12 weeks induced atrophy of the testes and accessory sex organs and a drop in immunoreactive pituitary and plasma prolactin levels. The subsequent exposure of these hamsters to LD 14:10 cycles caused regeneration of the sexual organs and an increase in pituitary LH and prolactin levels. Likewise, the weekly treatment of dark-exposed hamsters with subcutaneous melatonin-beeswax pellets led to regeneration of the peripheral reproductive organs and an increase in pituitary LH and prolactin levels. After gonadal regeneration, complete darkness failed to induce atrophy of the reproductive system indicating that either long photoperiods or melatonin treatment cause the pituitary-gonadal axis to be refractory to the inhibitory influence of darkness.


Endothelial DNA synthesis in themicrovasculature of rat skin during the hair growth cycle.

Earlier studies of the vascular patterns around hair follicles revealed that actively growing follicles have an extensive microvasculature relative to that around quiescent follicles. In order to determine whether the establishment of the active perifollicular vascular pattern involves replication of endothelial and perivascular cells, we studied the 3H-thymidine labeling indices of these cells in autoradiographs of rat skin from regions containing either actively growing follicles or recently inactive follicles. In skin containing inactive follicles, the endothelial labeling index was 0.22%, a figure similar to those reported for the endothelium of small blood vessels in several other non-stimulated adult tissues. However, skin containing actively growing follicles displayed an endothelial labeling index of 2.35%. The labeling indices of perivascular cells paralleled those of the endothelial cells. Thus, endothelial and perivascular cells in vessels associated with actively growing follicles undergo significantly more DNA synthesis than those in vessels associated with inactive follicles. Replication of these cells apparently contributes to the extension of the microvascular network around growing follicles.


Relationship between the adrenal cortex and thymic involution in "lethargic" mutant mice.

To determine if the adrenal gland plays a role in the thymic involution which occurs spontaneously in "lethargic" mutant mice, three different studies were made. Morphological studies were made first to determine if there was an indication of histological changes in the adrenal glands. Next, serum levels of corticosterone were measured by radioimmunoassay. Finally, mice were unilaterally adrenalectomized to see if such treatment would improve various symptoms of "lethargic" mutants. Results of the studies showed that lipid granules in the cortical cells of "lethargic"mutants were greatly reduced in number during the time of spontaneous thymic involution, and the mutant mice had a significantly higher level of serum corticosterone than the normal controls. Mutant mice unilaterally adrenalectomized at 15 days of age showed a marked improvement in their condition and their mortality rate decreased. It is concluded that spontaneous thymic involution of "lethargic" mutants is probably associated with adrenocortical hypersecretion.


A contribution to our knowledge of Leonurus L., i-mu-ts'ao, the Chinese motherwort.

This article deals with the ethnobotanical aspects of the Chinese motherwort. Since time immemorial the Chinese people have used various parts of motherwort to meet different physical needs. By the time a written language was developed and the medical uses were recorded. , motherwort was treated as an article of superior quality. At present, under the name of i-mu-ts'ao, the plant is used for improving bloodflow both by official physicians and herbal practitioners throughout the country as well as by villagers in isolated areas. According to Chinese classical literature on materia medica, the early uses were limited to the parts of the plant which met the most obvious needs of the prehistorical people in their struggle for existence-food and pain reliever. Evidently, in their search for food, the ancient people found that the four nutlets contained in the dry and spinose calyx of the Chinese motherwort resemble the seasame seed in size and oil content. They gathered them and used them for food in similar manner as with the sesame. Consequently, they discovered the good effects to the eyesight, the improvement of strength, and the uplift of spirit. These discoveries led to the use of the seed of the species as an eye medicine for improving the eyesight, and as a tonic for the increase of strength and the elevation of spirit. Contagious skin diseases caused serious problems for the ancient people. The use of the leafy shoot for a bath to release the discomfort of itches and shingles was also recorded in the 42-word first medicinal record of the species in the earliest known Chinese materia medica-the Shen-nung pen-ts'ao-ching. Translators of the Chinese classics have included the records of i-mu-ts'ao. According to my knowledge, these works are all partial translations with the selections of the medicinal properties and the omissions on the methods of preparation. They have the outline and abandon the details. Consequently most of them are not clear. In order to provide complete information on the discoveries of the ancient Chinese people on the uses of i-mu-ts'ao, all the records up to the end of the sixteenth century are organized and translated under the following headings: (1) ecological and morphological observations; (2) preparations; (3) physical and therapeutical properties; (4) special prescriptions for internal and external uses-including pills for pregnant women, for mothers post partum, as an emmenagogue, and as a corrective agent, condensed liquid, powder, fresh juice, baby bath and washes, poultices, charred shoots, gargles, drops and cakes; (5) other economic uses-including cosmetics and food; and (6) etymology. The distribution of i-mu-ts'ao is significant in photogeography and in the nomenclature of the species. I-mu-ts'ao was purposely introduced from South China to Linnaeus in Sweden before the publication of the Species Plantarum in 1753. Linnaeus planted the seed in the botanical garden of the University of Uppsala...


Extraction of hypotensive principles from seeds of Cassia tora.

Seeds of Cassia tora Linn. (Leguminosae) are known in Chinese medicinal herbal practice as Chueh-ming-tzu. Aqueous and methanol extracts from these seeds elicit hypotensive effects on anesthetized rats. Preliminary phytochemical studies show that the active hypotensive principles are derived from the kernel of the seed and consist of mainly glycosides.


A possible reflex mechanism of hypotensive action of extract from Cassia tora seeds.

The Chinese medicinal herb Chueh-ming-tzu, seeds of Cassia tora (Leguminosae) Linn., elicits hypotensive effects in anesthetized rats. Experimental results indicate that the hypotensive effect of the Cassia tora extract possibly involves a vagal reflex which reciprocally alters the vasomotor tone of the centrally emanating sympathetic nervous system. It is shown that the capacity of the Cassia tora extract to reduce blood pressure is significantly reduced in vagotomized rats and that hypotensive effects are greatly antagonized in rats whose sympathetic nervous systems are interrupted by transection of the spinal cord.


Induction of labor by acupuncture electro-stimulation.

Induction of labor by acupuncture electro-stimulation was carried out in 31 patients. This was successful in 21 cases. The pattern of uterine contractions induced in these patients was similar to that in normal labor. No serious fetal or maternal complications occurred. The delay between the commencement of stimulation and the onset of contractions suggests that a humoral mechanism may be involved.


Acupuncture for several functional disorders. Part I.

This is Part I of a study whose purpose is two-fold, that is, to arrive at a classification of diseases under investigation according to their responsiveness to acupuncture therapy, and to discuss and identify the most effective loci for the diseases investigated. In Part I of this study, over 500 patients afflicted with hyperthyroidism, trigeminal neuralgia or intercostal neuralgia were treated with acupuncture therapy. The results of the treatment, together with the selection of acupuncture loci and the techniques of needle manipulation are reported in detail. Over 80% of the patients were found to have made excellent improvement. The three diseases are therefore classified as diseases on which acupuncture therapy yields excellent results.


ECT and Acu-EST in the treatment of depression.

This paper presents three brief case histories from a three year study comparing electroconvulsive therapy (ECT) with acupuncture treatment in functional psychoses. Acupuncture effects were augmented by the simultaneous, non-painful electrical stimulation of eight acupuncture needles. The resulting treatment is called Acupuncture Electric Stimulation Therapy (Acu-EST). Each patient was utilized as her own control, treating exacerbations of depression alternately with ECT and Acu-EST. Acu-EST was not found to be a panacea and did not enable the discontinuation of antidepressant and neuroleptic medication. Individual Acu-EST treatments were often less effective than individual ECT treatments. However, series of Acu-EST did assist in producing significant remissions in depressive symptomatology. Because it did not produce the temporary disabling memory defects which occurred with ECT, Acu-EST was more easily adaptable to outpatient treatment.


A new technique for the insertion of acupuncture needles.

A new technique to insert acupuncture needles into the tissue without touching the needle with the fingers of the acupuncturist was developed by the authors. It is easy to perform and completely eliminates the problem of contamination. The bending of the needle is less frequent and the pain sensation of the patient is also minimized.


Medical education in China.

This article concerns the changes in Chinese medical education which have taken place since the Cultural Revolution, specifically the relationship between political ideology and actual practice. It synthesizes the documentation which appeared in a series of articles devoted to a public discussion on the direction and emphasis in medical and health work published in Renmin Ribao (People's Daily), Peking, from December 8, 1968 to November 4, 1975. The major themes of the public discussion are: (a) medical and health work serving the masses; (b) insistence on the "correct" revolutionary line; (c) combining theory with practice; (d) unity of traditional Chinese and Western medicine; (e) putting prevention first; and (f) emphasis on medical personnel retaining the characteristics of the working people. This is followed by a transcript prepared by the authors from a tape recording made during a visit to Zhongshan Medical College of Guangzhou (Canton) on November 5, 1974 describing the relationship between political ideology and actual practice in the field of contemporary Chinese medical education.


The effects of 0.1 and 1.0 per cent erythrocytes and hemolysis on serum chemistry values.

Changes in serum chemistry values as a result of incomplete removal of erythrocytes and in vitro hemolysis during the preparative process have been studied. Two levels of contamination, corresponding to removal of 99% and 99.9% of the erythrocytes, were used to examine the effects of both hemolyzed and intact cells. Forty chemical procedures and methods were considered. Serum LDH values were most strongly affected by hemolyzed erythrocytes. Potassium, creatine phosphokinase, aspartate aminotransferase, alanine aminotransferase, and iron showed smaller but significant effects due to the presence of 1% hemolyzed cells, with lesser effects observed at the 0.1% level. The presence of non-hemolyzed cells at either level did not significantly alter chemistry results.


Effects of specimen evaporation on quality control.

Serum samples stored in a refrigerator and in ambient room air were studied for alteration of mean weight and mean concentration values. The storage period selected was four hours and the samples were variously stored exposed, refrigerated, and covered with a sample tray cover and by an airtight cover. Some storage procedures produced values more than 2 SD from the mean for many analytes. These findings were confirmed by a parallel study revealing a decrease of sample weight after the four-hour storage period. Storage at 4 C in sample cups covered by an airtight opaque shield alleviated the problem. Failure to treat external quality control sample pools in the same way as other samples will produce unexplained out-of-control results.


Assessment of the serum separator tube as an intermediate storage device within the laboratory.

An integral blood-drawing-serum separator tube, (SST) is evaluated for use as an in-laboratory serum storage device. Sera stored in the SST were compared with paired controls that were specimens from the same subjects stored in closed culture tubes. Eighty-six serum chemistry determinations showed no clinically significant change as a result of 48 hours of storage in the original blood-drawing tubes. Storage of serum in this manner provides the laboratory with specimens for reanalysis or additional analyses while eliminating manipulative steps, including serum removal, tube relabeling, and intertube transfers, and reducing errors due to misidentification and/or contamination.


Sources of error in glucose determinations in neonatal blood by glucose oxidase methods, including Dextrostix.

An investigation was carried out to examine why a glucose oxidase-peroxidase-orthodianisidine method for plasma glucose, without protein precipitation, gave low results for neonatal blood. The magnitude of the difference between the results with and without protein precipitation was examined in a clinical neonatal series, and in sera to which bilirubin, hemolysate, pure hemoglobin, and uric acid had been added. Systematic linear inhibition was demonstrated with bilirubin, and the results suggested that high concentrations of hemolysate and uric acid could also interfere. Use of alkaline protein precipitants eliminated the inhibition. Dextrostix test results for neonatal blood are compared with results of conventional glucose analyses and possible sources of discrepancy examined.


New diagnostic use of bone marrow acid and alkaline phosphatase.

Prostatic acid phosphatase and alkaline phosphatase values in bone marrow were correlated with skeletal surveys and diagnoses during a six-month study. In cases of biopsy-proven adenocarcinoma of the prostate, bone marrow prostatic acid phosphatase was the most consistently abnormal value. Diagnoses other than prostatic cancer involving the bone marrow, e.g., myeloma and leukemias, were associated with elevated prostatic acid phosphatase and alkaline phosphatase values. In cases in which the bone marrow was not involved by metastasis, these values were normal. Bone marrow prostatic acid phosphatase assay was found to be a very good tool for detecting early osseous metastases from any site, including prostatic adenocarcinoma.


Hemangiopericytoma-like intranasal tumors. A clinicopathologic study of 23 cases.

The clinical, microscopic, and gross pathologic features of 23 cases of intranasal hemangiopericytoma-like tumors are reviewed and studied. When in the nasal cavity, these lesions often originated in a paranasal sinus and extended into the nasal cavity secondarily. They occurred most commonly in adults in the sixth and seventh decades of life; there was no significant sex predilection. Twenty-two of the 23 patients were Caucasian. These patients most commonly had symptoms of nasal obstruction and epistaxis. Clinically the lesions were generally thought to represent allergic polyps. Although appearing microscopically as non-differentiated spindle-cell neoplasms, these lesions showed little nuclear or cytoplasmic pleomorphism, minimal mitotic activity, and no necrosis or hemorrhage or other evidence of anaplasia found in malignant tumors. Follow-up data showed no evidence to suggest a malignant or biologically unpredictable lesion. Nineteen of 22 cases followed showed no recurrence regardless of the treatment; those that recurred did so locally. No metastasis or other form of aggressive behavior attributed to hemangiopericytomas in other anatomic locations was seen in this series. Another case, diagnosed as a malignant hemangiopericytoma of the nasal cavity, showed dissimilar and anaplastic histologic features. This case metastasized and is discussed, though not included in this study.


Hepatic lesions of central pericellular fibrosis in morbid obesity, and after jejunoileal bypass.

Histologic findings in liver biopsy specimens obtained from 88 patients before and one and two years after end-to-end jejunoileal bypass are compared. In addition to the expected fatty changes, mild changes of centrilobular, pericellular fibrosis were present in the initial biopsies in 8.6%; a year later they had become apparent in 46%. Portal-central bridging developed in 6.8%, and early micronodular cirrhosis in 3.4%--always in those with central pericellular fibrosis. Electron-microscopic study of pre-bypass liver biopsies from eight addtional patients showed collagen and electron-dense material resembling basement membranes within the spaces of Disse in seven, although only four had light-microscopic evidence of minimal central pericellular fibrosis. The existence of these light- and electron- microscopic changes before jejunoileal bypass suggests that there is a lesion in morbid obesity that may be exacerbated during the first year after operation.


Rhabdomyosarcoma in children. A clinicopathologic study of 35 patients.

Thirty-five patients with rhabdomyosarcoma were treated at the Children's Hospital Medical Center from 1953 to 1973. Factors important in diagnosis and prognosis included age, sex, site, stage of tumor, and specific pathologic type. Effects that surgery, radiation, and chemotherapy had on survivals were also analyzed. Survivals ranged from 2 to 20 years. The rates were 86% for Stage I disease; 40% for Stage II disease, and 0 for the more advanced lesions. A useful prognostic indicator was found in pathologic subgroupings. Survivals for the myxoid spindle-cell variant were 80% for all stages. For the partial maturation series with moderately well-differentiated rhabdomyoblasts, survival was 10% for all stages. For a combination of the above two types, survival was 40% for all stages. The alveolar types had no survivors, although these patients seemed to live longer with their disease.


The adrenal cortex in cystic fibrosis of the pancreas.

The morphologies of the adrenal cortical zones of 25 children with cystic fibrosis and 24 control patients are presented. A technic for objective measurement of these zones is described. Hyperplasia of the zona glomerulosa in the children with cystic fibrosis is significant and may be related to chronic loss of salt in the sweat or demands placed on renal salt-conserving mechanisms.


Small-cell carcinoma of the male mammary gland. A tumor resembling infiltrating lobular carcinoma.

The cases of two patients with infiltrating lobular carcinoma of the male mammary gland are discussed. They represent two of a total of 16 male patients with mammary carcinomas examined at the Medical College of Virginia between 1950 and 1975. Two previous similar cases have been reported in the literature as "small-cell" carcinoma. In one of the current cases there is unexplained benign lobular proliferation with atypical features suggesting lobular origin of the infiltrating tumor.


Probable acanthamoeba meningoencephalitis in a Korean child.

A 5-year-old Korean boy developed multiple subcutaneous, nontuberculous granulomas and died with meningoencephalitis. Autopsy disclosed amebic granulomas in subcutaneous tissue, the left adrenal gland, and the pancreas, with more acute inflammatory lesions in the liver, kidney, and brain. The causative organism is believed to be an Acanthamoeba sp.


Laboratory diagnosis of botulism complicated by pyridostigmine treatment of the patient. A method for selectively removing interfering substances from clinical specimens.

In August 1974, a case of botulism occurred; home-canned potatoes and peas containing Clostridium botulinum, type A, were strongly incriminated as the vehicle of transmission. C. botulinum, type A, was isolated from a stool specimen of the patient, but the mouse neutralization test for botulinal toxin could not be completed because the stool extract contained a highly toxic, heat-stable substance that rapidly killed mice. Historical and laboratory evidence indicated that the substance was pyridostigmine bromide, a low-molecular-weight drug with which the patient had been treated after her disease was misdiagnosed as myasthenia gravis. A generally applicable method employing dialysis by which toxic SUBSTANCED of low molecular weigth could be selectively removed from specimens without diminishing the potency of botulinal toxin contained in them was developed. Dialysis rendered a pyridostigmine solution, a stool extract from the patient with botulism, and a stool extract from a person taking pyridostigmine virtually nontoxic to mice. Dialysis did not significantly alter the toxicity to mice of crude botulinal toxin; it selectively eliminated all or almost all pyridostigmine toxicity from a pyridostigmine-botulinal toxin mixture without altering the toxicity of the botulinal toxin.


Mapping of several abnormal hemoglobins by horizontal polyacrylamide gel isoelectric focusing.

The relative mobilities of serveral human hemoglobin variants were studied by use of an isoelectric focusing method in a thin-layer horizontal polyacrylamide gel. The technic is described in detail and a preliminary mapping of these variants is presented. It appears that thin-layer gel isoelectric focusing is a method that is rapid, highly reproducible and easily applicable in laboratories concerned with the study of hemoglobinopathies.


Effects of patient racial attribution on black clinicians' inferences.

This study was done to determine the impact of patient racial attribution on black practitioners' clinical judgments. Fifty-five professionals indicated their clinical reactions to a bogus case description of a sexually maladjusted male patient identified as black or white and also completed a traditional social beliefs scale. Relatively untraditional clinicians evaluated the black-designated patient more favorably than the white-designated patient. The less traditional practitioners also evaluated the black-designated patient more favorably than did the traditional clinicians. Effects of patient race were found for both clinical impressions and treatment decisions and were not attenuated in the more highly experienced subsample. Implications and limitations of the findings are discussed.


Untrained paraprofessionals' verbal helping behavior. Description and implications for training.

The verbal behavior of untrained paraprofessionals in simulated initial helping interactions was studied. Taped interviews conducted by 131 helpers-in-training were evaluated on the Helping Skills Verbal Response System, a category system consisting of continuing, leading, and self-referent responses. Helpers were found to vary considerably in number and types of responses given. Leading responses were twice as frequent as continuing responses. The most often used response was the closed question. Few responses focusing on helpees' feelings were given. The implications for training were discussed in terms of the facilitative role of helpers in initial helping interactions.


The development and evaluation of a community mental health education program for seminarians.

Because the clergy stands in an ideal position to serve the mental health needs of the community, seminaries have, for some time, included courses in pastoral counseling and related skills. While valuable, these courses tend to focus on the traditional clinical relationship excluding the broader role of community interventionist. Viewing this need, a course was developed to train seminarians in principles and practices of community mental health. The 28 students were compared to 24 controls at the beginning and end of the term. Evaluative instruments were the Community Mental Health Ideology Scale, two scales adapted from the Theological School Inventory, a self-evaluative competence scale, and a role evaluation scale. Data within a 2 X 2 X 2 design were subjected to an analysis of variance. Experimentals were found to exceed controls on the Community Mental Health Ideology Scale (p less than or equal to .001), the competence scale (p less than or equal to .01), and role evaluation scale (p less than or equal to .01).


Evaluation of crisis intervention services with anonymous clients.

A technique is introduced for using intake data to evaluate crisis intervention services in which client anonymity prevents the usual follow-up procedures. The technique is based on the assumptions (a) that the rate of reuse of the service indicates the effectiveness of the service, and (b) that counselors' estimates of their effectiveness provide some indication of the adequacy of their training. The study was conducted at a 24-hour metropolitan hotline. In addition to obtaining the usual intake information, counselors asked callers how often they had used the hotline previously and then rated their own effectiveness in aiding the callers. Analyses show the relative effectiveness of the hotline with various types of callers and problems and suggest areas where additional counselor training is desirable.


Evaluating the crisis service of a community mental health center.

This paper describes the use of an empirically based evaluation system for the Crisis Service of a comprehensive community mental health center. Through cooperative agreements with community agencies, jailings of behaviorally disturbed individuals have decreased in number and duration. Evaluations have also measured response time and success of recommendations made by workers. The authors describe how the Crisis Service's  evaluation techniques reflect the Center's commitment to accountability, a behavioral approach, and community orientation. Data concerning evaluation of the service are presented.


Hyperamylasemia in heroin addicts. Characterization by isoamylase analysis.

Hyperamylasemia was noted in 17 (19%) of a group of 91 hospitalized heroin addicts. Thirteen of the 17 were in acute respiratory distress (12 with so-called "heroin lung" syndrome and one with status asthmaticus). Isoamylase analysis in the hyperamylasemic patients demonstrated S-type isoamylase dominance in 15, P-type isoamylase dominance in one and essentially equivalent P- and S-type isoamylase elevations in one. It would appear from these data that the hyperamylasemia after heroin in most persons addicted to the use of this drug arises from the sources other than the pancreas. Changes in the lungs occurring in association with heroin addiction seem to have an important role among the possible contributory factors.


Colonscopic excision of sessile polyps.

Most benign sessile colon polyps can be removed colonoscopically from all reaches of the colon, thus avoiding laparotomy previously required for most of these lesions. Two hundred and fifty colonoscopy procedures were reviewed, revealing 87 sessile colon polyps ranging from 0.5-6.0 cm. in size. Sixty-eight of 87 lesions were excised from 51 patients with just three lesions found to be malignant (invasive adenocarcinoma). Sixteen lesions were felt to be unsuitable for safe colonscopic excision and were, therefore, removed by laparotomy (in 12 patients) and six lesions found to be malignant. Three sessile lesions in this consecutive series were not yet removed at the time of this writing. Thorough bowel preparation and evaluation for other possible lesions are important components of this procedure, which yielded other polyps or cancers in 24 of 66 patients. While most sessile lesions less than 2 cm. in size can be excised endoscopically, certain larger benign sessile lesions can also be removed using piece-meal snare excision technics and radiowave electrocautery (principle of less heat penetration and tissue destruction). Seventy-nine per cent of all sessile colon polyps were excised colonoscopically in this series making abdominal surgery now unnecessary for most colon polyps. Laparotomy is necessary for certain larger benign lesions and all sessile lesions containing invasive cancer.


Tuberculous peritonitis. A case report and review.

A 32-year old Dominican woman with signs and symptoms of an acute abdomen, was found to have tuberculous peritonitis. Our experience with this patient is presented along with a review of the literature. Population shifts may bring about an increased number of cases in this country. Awareness of this entity will avoid unnecessary diagnostic errors and laparotomy. The surgeon should also be versed in the total management and be prepared to handle the surgical complications of the disease.


Benign lymphoid hyperplasia of the stomach mimicking gastric malignancy.

A case of benign lymphoid hyperplasia of the stomach misdiagnosed as ulcerating gastric carcinoma is presented. The similarities in the clinical, roentgenologic and and gastroscopic features as well as in the gross appearance of the two lesions are described and the features which help differentiation are highlighted. The pathologic picture suggested that the lesion possibly arose as a peptic ulcer and the clinical history further supports such a possibility.


Optimum dose of histamine for maximal acid output in underweight subjects.

The effects of increasing doses of histamine acid phosphate on the gastric secretion of acid has been studied in a randomized fashion in five normal control and 15 duodenal ulcer subjects. The dose of histamine acid phosphate used in each individual was 40, 70, 76 and 80 mug/kg. and 3.2 mg. of histamine. In 12 of 20 subjects the highest mean +/- S.D. acid output was observed after a dose of 76 mug./kg. body weight. When the acid output was expressed as the percentage of the highest response with different doses of HAP, the response was maximum with 76 mug. kg. dose. Further statistical analysis by rank totals and X2r by Friedman's two-way analysis by ranks also revealed highest acid output after a 76 mug./kg. dose of HAP. These findings suggest that 76 mug./kg. is the optimum dose for maximal acid output in underweight subjects. Only one patient showed highest acid output after a 3.2 mg. dose of histamine. The mean +/- S.D. acid output after 76 mug./kg. was higher than that after a 3.2 mg. dose of histamine. Hence, for estimating maximal acid output, a weight related dose and not a fixed dose is recommended. Further, it was shown that there was significant correlation between PAO and MAO after various doses of histamine in both the groups. Hence, for clinical purposes, estimation of one hourly poststimulatory maximal acid output after a dose of 76 mug./kg. body weight of histamine acid phosphate is recommended for underweight subjects.


Afferent loop syndrome: a different picture.

A patient who had a 50% gastrectomy with a Billroth II gastrojejunostomy one and a half years previously, complained of recent severe weakness as the only symptom was found to have an iron deficiency anemia with a periumbilical mass. A gastrointestinal series showed a soft tissue density in the epigastric area which, by ultrasonography, was found to be fluid-containing. Laparotomy revealed obstruction of the afferent loop caused by a marginal ulcer.


Carcinoma of the gallbladder: a diagnosis aided by endoscopic retrograde and percutaneous hepatic cholangiography.

In a patient with obstructive jaundice, extrinsic compression of the common bile duct (Mirizzi syndrome) due to squamous cell carcinoma of the gallbladder was documented with the combination of endoscopic retrograde cholangiography and pancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC).


Chymotrypsin output in the stools in pancreatic and other diseases.

Chymotrypsin output in the stools (u./24 hr.) has been calculated from analysis of single stool samples, using cuprous isothiocyanate as a continuous marker. The values thus calculated agreed favorably with those calculated from three-day stool collections. In 45 controls, with and without steatorrhea, chymotrypsin output was above 10,000 u./24 hr. In six patients with pancreatic insufficiency the values were considerably lower. In 10 patients with pancreatic disease without insufficiency the values were in the normal range. The method was found very useful in the diagnosis of pancreatic insufficiency. It was not sensitive enough to detect lesser degrees of pancreatic damage.


Studies on factors affecting healing of gastric ulcer. A prospective, cooperative study in Japan.

To assess factors influencing the healing of gastric ulcer, a prospective and cooperative study was carried out in Osaka, Japan. Four hundred nineteen patients with single gastric ulcer were followed from May, 1971 to June, 1973. These patients were divided into two groups, "healing" and "delayed healing", on the basis of the criteria by the distribution analysis. By the multivariate analysis of 11 factors picked up, site, size of the ulcer and age were related to healing of gastric ulcer with the larger weight. These results suggest that ulcers of smaller lesions, ulcers of the gastric body, ulcers of the anterior wall or younger patients show faster healing in general.


The microcirculatory correlator: a new instrument for the intraoperative evaluation of visceral circulatory integrity.

The microcirculatory correlator probe has been used on multiple occasions on the abdominal viscera and clear pulse-wave tracings have been obtained from all the intra-abdominal organs. There is a linear correlation between deflection of pulse-wave and intestine blood flow in an isolated loop of intestine under low flow conditions. The probe has been used in two circumstances to good clinical advantage.


Fine needle cholangiography in the diagnosis of persistent jaundice. A case report.

The fine needle technic utilizes a sleeveless, thin, flexible needle for transhepatic cholangiography. This needle can enter small or normal bile ducts in a high percentage of patients. The value of fine needle cholangiography is illustrated in a patient with a stenosis of the common hepatic duct and a left hepatodochalduodenal fistula which eluded diagnosis by all other methods. The use of this technic is described as an alternative procedure to endoscopic retrograde cholangiography when the latter is technically impossible or as an adjunct to intraoperative extrahepatic cholangiography.


A rapid, manual test for amylase at 52C.

A simple modification of an alpha-amylase (E.C. 3.2.1.1.) procedure, using blue starch substrate, permits quantitative results after three minutes of incubation. The procedure, performed on blank, control, and unknown speciemns, takes advantage of the heat stability of the enzyme and provides immediate and reliable data for acutely ill patients. The performance characteristics of the test on serum and urine are described. The method is distinctly advantageous in prividing rapid results for serum amylase, urine amylase, and amylase clearance in patients with suspected pancreatitis.


Practical aspects of quality control for radioimmunoassays.

Mechanisms for the quality control of radioimmunoassays are described. They are useful in monitoring the possible sources of error which cause medically invalid results: errors in the radioimmunoassay system itself, in the test environment, in the instrumentation, and in the specimen quality. The application of a total control program permits early detection of malfunctions and can be used for the logical assessment of probable causes and solutions.


Automatic blood film preparation by rheologically controlled spinning.

During the past six years at the Biomedical Technical Center of Corning Glass Works, extensive studies on blood film preparation have resulted in a method and an instrument which offer the hematology laboratory better quality than that routinely attainable with the conventional wedge or cover-slip techniques. This spinning method provides the operator with a uniform blood "film" whose cell type distribution accurately reflects the distribution of the original liquid blood sample instead of a "smear." This film improves the accuracy of white blood cell differential counts performed manually; it also enhances the accuracy of recently developed machines which automatically locate and classify leukocytes.


Cognitive processes and academic achievement in EMR adolescents.

Twelve cognitive process variables were investigated as predictors of reading and arithmetic achievement and studied for internal structure, with 115 EMR adolescent subjects. Stepwise regression and factor analyses were employed to study prediction and structure, respectively. Memory variables were the most important predictors of reading. They were also involved in arithmetic but to a lesser extent. The data suggested that the ability to generate and utilize strategies facilitating the recall of unstructured material as well as the capacity to be sensitive to strategy-relevant structure embedded in stimuli were important prerequisites for the acquisition of reading skills. An oddity task, measuring the ability to maintain the same relational focus for successive applications to new stimulus material, was found to be most pertinent for predicting arithmetic computational skills.


Dimensions of adaptive behavior of retarded and nonretarded public-school children.

The AAMD Adaptive Behavior Scale, Public School Revision, was administered to 2,618 elementary-school children from 7 to 13 years of age. The sample of children included White, Black, and Spanish-surname groups from regular and special-education classes. Factor analyses of domain scores indicated four dimensions of adaptive behavior: Functional Autonomy, Interpersonal Adjustment, Social Responsibility, and Intrapersonal Adjustment. Comparison of factor structure across school classification and age groups revealed the same four dimensions for all groups. Implications for the assessment of adaptive behavior were discussed.


Treatment of self-injurious behavior by a combination of reinforcement for incompatible behavior and overcorrection.

In two related studies, a combination of reinforcement for incompatible behavior and positive practice overcorrection was applied to the elimination of head-slapping and head-banging behavior exhibited, respectively, by two profoundly retarded boys. The design for both studies also included a period in which only reinforcement for incompatible behavior was applied. The results from Study 1 indicated that, while reinforcement had little effect in reducing the frequency of the learner's head slapping, the combination of reinforcement and overcorrection had an immediate effect in significantly reducing and eventually eliminating that behavior. A 4-month follow-up indicated no significant recurrence of the behavior. In Study 2, on the other hand, both reinforcement and the combination of reinforcement and overcorrection resulted in a significant increase in the frequency of the learner's head-banging behavior. Discussion centered on several research questions left unanswered by the differing effects of the procedures applied in both studies.


Ethnicity, geographic locale, age, sex, and urban-rural residence as variables in the prevalence of mild retardation.

The Wechsler-Intelligence Scale for Children-Revised (WISC-R) was administered to 950 of a stratified random sample of 1,040 children in Pima County, Arizona. The sample was stratified for ethnicity (Anglo, Black, Mexican-American, and Papago Indian), urban-rural residence, sex, and grade level. The three WISC-R IQ scores and cutoff points of 69 and 75 were used in comparisons of prevalence of mild mental retardation. This prevalence was significantly related to ethnicity and geographic locale. Sex, urban-rural residence, and grade level were not related to prevalence.


Path analysis of parents' conservatism toward sex education of their mentally retarded children.

The authors investigated three probable reasons why parents of mentally retarded children would be opposed to sex education being offered as a school subject: general sexual attitudes, specific sexual attitudes, and prejudices against the retarded child's own sexuality. A questionnnaire was given to 60 parents of retarded children and 62 parents of nonretarded children. A correlation analysis revealed evidence of all three kinds of reasons and led to a causal model of conservatism on sex education. A path analysis revealed that (a) sexual prejudices are a major obstacle to sex education, and (b) each group of parents represents a specific dynamic of conservatism on sex education. Means of pedagogical intervention to modify parents' attitudes toward sex education of handicapped children were discussed.


Comparison of nonretarded and mentally retarded children on a perceptual learning task.

The performances of 12 EMR and 12 nonretarded sixth-grade children on a perceptual learning task were compared to investigate the information processing of visually presented stimuli in individuals with different intelligence levels. A minicomputer flashed either familiar (lowercase) or unfamiliar letters (Gibson-like figures) in either a stimultaneous or successive mode on a same-different matching task. The computer automatically calculated accuracy and latency data for each subject. Results showed that accuracy was superior in the nonretarded group and that mean latencies for the EMR group was consistently higher than those of the nonretarded group. However, when latencies were corrected for differences in basic reaction time, there were no significant differences between the groups in the speed of processing the information.


Effects of price manipulations on consumer behavior in sheltered workshop token economy.

The consumer behavior of institutionalized retarded clients in a sheltered workshop token economy were evaluated by changing prices in the workshop store. In the first experiment we found that clients displayed elasticity of demand in that raising the prices of frequently purchased goods reduced the frequency and amount spent on more expendable items. Results from the second experiment showed that this change in spending pattern was not due to the relative modal unit price of item classes. The regulation of demand for consumer goods is a potentially useful way to maintain economic balance and effectiveness of a token economy.


TMR children's competence in processing negation.

Previous researchers have suggested that TMR children lack the competence to process negation. Questions about the appropriateness of using reversible sentences to test comprehension and observations on TMR children's imitative processing of simple affirmative and negative sentences led to an experimental reexamination of the earlier findings. Institutionalized students ranging in age from 10 to 21 years with a mean IQ of 30 were asked to evaluate 16 picture pairs, 8 each for nonreversible and reversible sentences. Nonreversible sentences, both positive and negative, were interpreted correctly more often than reversible sentences. There was a significant correlation between comprehension and mental age. The results were interpreted as substantiating the adverse effect of sentence reversibility on comprehension and as evidence for the position that retarded children develop basic grammatical structures including negation at a relatively late age, but in normal interrelationship and sequence with other language and cognitive abilities.


Note of an error in "Action Concept Usage by nonretarded and retarded children on structured tasks with praise for performance".

An error in calculation of MAs of the moderately retarded subjects in the above study raises significant questions about the findings that their use of action concepts is less than that of mildly retarded subjects of the same MA. Their reduced performance may instead be attributable to some unknown extent to their lower MA.


Dominantly inherited cystoid macular edema.

An apparently autosomal-dominant macular dystrophy occurred in three pedigrees with the presenting signs of typical cystoid macular edema due to leaking perimacular capillaries. Other striking features were retinal capillary leakage all over the posterior pole of the eye, whitish punctate deposits in the vitreous body, a normal electroretinogram, a subnormal electro-oculogram, and moderate to high hyperopia. In later or more advanced stages the macula developed a central zone of "beaten bronze" atrophy. Strabismus occurred frequently.


Fluorescein angiography with an optimized filter combination.

The transmission characteristics of a new filter combination for fluorescein angiography were selected on the basis of in vivo measurements of the excitation and emission spectra of fluorescein dye during its transit in the fundus. This combination of filters was characterized by separation of 530 nm between the spectral ranges of transmission of the excitation and barrier filters. In the standard filter combinations this separation is at about 495 nm. Compared to the standard filters, the new filters enhanced the film exposure for all sites of the fundus, especially for the macular area and choroidal fluorescence. There was an improvement in demonstration of the choroidal vasculature, especially in the macular area, and better visibility of retinal detail in the macular area, but a slight decrease in contrast of the retinal vessels outside the macular region. Improved visibility of the fundus for the observer and reduction of scattering in the ocular media of older subjects improved the overall quality of angiograms made with the new filters.


Acute pulmonary edema following intravenous fluorescein angiography.

A 64-year-old white man with no history of cardiac or bronchopulmonary disease developed acute pulmonary edema shortly after undergoing diagnostic intravenous fluorescein angiography. The patient responded quickly to a course of oxygen, positive pressure breathing, diuretics, and sedation.


The Miami cooperative community study on the Copeland intraocular lens (pseudophakos).

We reviewed 623 cases of Copeland iris plane implantation in an elderly population. Sixty-three percent of eyes achieved visual acuity of 6/12(20/40) or better. The incidence of significant corneal edema was low. Postoperative problems included cystoid macular edema, membranous-like structures, and iritis.


Intraocular penetrating of amoxicillin.

The enucleated eyes of New Zealand albino rabbits were injected with 50, 100, 250, and 500 mg/kg of amoxicillin to determine the drug penetration into the aqueous humor, vitreous humor, serum, and other ocular tissues after oral administration. Detectable levels were achieved after each specific dose for at least five hours. In the aqueous humor, drug levels were present at 15 minutes, peaked at 1.5 and two hours, and were present at leave five hours after oral administration.


Experimental intravitreal gentamicin.

Rabbits received intravitreal injections of gentamicin and indirect ophthalmoscopy, electroretinography, and histopathology determined relative toxicity. An intravitreal dose of 0.1 to 0.2 mg of commercially available gentamicin was well tolerated in the rabbit eye. A dosage of 0.4 mg or higher consistently produced significant ocular toxicity as evidenced by extinction of the electroretinogram, gross fundus changes, and histopathologic alterations.


Levodopa-stimulated growth hormone secretion and diabetic retinopathy.

Since growth hormone has been implicated as a possible etiologic factor in the development of diabetic retinopathy, we examined growth hormone levels in two groups of growth-onset diabetics matched for age and duration of disease. The experimental group had definite proliferative diabetic retinopathy; the control group of growth-onset diabetics had no significant retinopathy. Basal and levodopa-stimulated levels of growth hormone were determined for each group. Growth hormone response could not be correlated with the presence or absence of diabetic retinopathy (P less than .05).


Spontaneous hyphema associated with ingestion of aspirin and ethanol.

Unilateral hyphema, hematuria, and ecchymoses developed in a previously healthy 42-year-old women after the ingestion of aspirin and ethanol. There was no evidence for ocular trauma, disease, or vascular malformation by slit-lamp examination and gonioscopy. Platelet count and coagulation tests were normal. The patient's bleeding time was prolonged and there was impaired platelet aggregation. Delayed (secondary) aggregation in response to collagen, adenosine diphosphate, and epinephrine was decreased, as was aggregation induced by thrombin and serotonin. These data indicate that the qualitative platelet defect was induced by both aspirin and ethanol. Anterior chamber hemorrhage subsided after discontinuation of aspirin and ethanol, and the hyphema subsequently resolved. Bleeding time and platelet aggregation were normal two weeks after the patient's initial presentation. A prolonged bleeding time in association with normal platelet count, prothrombin time, and partial thromboplastin time indicated a qualitative platelet defect, which is most commonly drug-induced. Defective platelet function resulted in spontaneous hyphema.


Spontaneous cyclic segmental sphincter spasms in an Adie's tonic pupil.

A 43-year-old woman with bilateral Adie's tonic pupils had a segment of one iris sphincter that contracted spontaneously every few seconds, but was not influenced by light, near vision, or eye movements.


Management of the thumb-index web space contracture.

This paper focuses on the management of the thumb-index web space contracture, a contracture that can interfere significantly with hand function. The anatomy of the thumb-index web space and the contracture mechanism are reviewed. Contractures frequently result from traumatic hand injuries involving the web space or peripheral nerves. Exercises and splinting techniques for preventing or correcting these contractures are directed at achieving and maintaining maximum range of motion and strength of the thumb. Case reviews are reported that show improvements in range of motion measurements of 31 patients treated with the described techniques.


3 theoretical approaches to play: applications for exceptional children.

Three theories of play are reviewed and discussed in terms of their applicability to exceptional children. The theories--Freud's psychodynamic, Piaget's developmental, and Ellis' arousal-seeking--are compared on the basis of: 1. the validity of their constructs, 2. their ability to account for behaviors of exceptional children, and 3. the likelihood that they could generate future play research with an exceptional population. It was concluded that the only theory that could hope to meet these requirements at this time was the arousal-seeking theory of Ellis.


Components in program development.

There has been a great deal of discussion and deliberation concerning the composition of program development. Nonetheless, the question still remains--what is program development? What are possible components in program development? In this paper the following components are described, differentiated, and integrated: Statement of Purpose, Curriculum Design, Program Competencies, Content, Content Competencies, and Practice Environments.


The role of environmental ammonia in respiratory mycoplasmosis of rats.

Young adult, pathogen-free rats of Sherman and Fischer (F344) substrains were inoculated intranasally with 10(8) colony-forming units (GFU) of M. pulmonis and housed for 4 to 6 weeks in environments with ammonia maintained at specific concentrations from 25 to 250 ppm. All levels of NH3--whether produced naturally from soiled bedding or derived from a purified source--significantly increased the severity of the rhinitis, otitis media, tracheitis, and pneumonia (including bronchiectasis) characteristic of murine respiratory mycoplasmosis (MRM). The prevalence of pneumonia, but not that of other respiratory lesions of MRM, showed a strong tendency to increase directly with environmental NH3 concentration. In contrast, NH3 exposure of rats not infected with M. pulmonis caused anatomic lesions that were unlike those of MRM and were limited to the nasal passages. It was concluded that environmental NH3, at concentrations commonly encountered in present day cage environments for rats, plays an important role in pathogenesis of MRM.


The pathology of viral hepatitis types A and B in chimpanzees. A comparison.

The histologic manifestations in the livers of chimpanzees inoculated with hepatitis A and B virus were compared with each other and correlated with biochemical, serologic, and virologic observations. Both types of hepatitis reveal alterations similar to those seen in human hepatitis, but the lesions--particularly the hepatocellular necrosis--are far milder. Hepatitis Type A in chimpanzees is a disease of short incubation period and duration. The hepatocytic alterations are mainly restricted to the periportal areas, and the parenchymal changes are less severe than the portal inflammation. The lesions correlated well with biochemical changes, the presence of virus in the liver, and its shedding in the stool. In contrast, experimental Type B hepatitis has a long incubation period and longer duration, involves the entire lobular parenchyma, and is, if anything, more severe in the lobular centers while portal inflammation is less conspicuous. Biochemical alterations and presence of virus in the liver correlate with these lesions, and the antibody response is similar to that seen in man. The chimpanzee is a useful model for studying the pathogenesis of viral hepatitis; additional study of serial morphologic events may contribute to our understanding of the clinical differences between hepatitis Type A and Type B.


Isolation of myotoxic component from rattlesnake (Crotalus viridis viridis) venom. Electron microscopic analysis of muscle damage.

The pathogenesis of myonecrosis induced by a purified component of rattlesnake (Crotalus viridis viridis) venom was studied at the light and electron microscopic levels. Crude venom was fractionated by gel filtration (Sephadex G-50) followed by cation exchange chromatography (Sephadex C-25). Electrophoretic homogeneity of the isolated myotoxin (Fraction II from C-25 column) was demonstrated in isoelectric focusing and disc gel polyacrylamide gel electrophoresis. White mice were injected intramuscularly with 1.5 mug/g of the purified protein in 0.1 ml of physiologic saline. Light microscopic examination of injected muscle revealed a series of degenerative events including partial vacuolation of muscle cells at 6, 12, and 24 hours and complete vacuolation and loss of striations at 48 and 72 hours. Hemorrhage was not observed. At the electron microscopic level the perinuclear space and sarcoplasmic reticulum were dilated in all samples. By 48 and 72 hours the myofibrils lacked striations and the sarcomeres were disorganized. Plasma membranes and T tubules remained intact in all samples. These results correlated well with the myonecrosis induced by crude Crotalus viridis viridis venom except for several important aspects. The pure component altered skeletal muscle cells specifically, with the sarcoplasmic reticulum being the primary site of action.


Ultrastructural observations on experimentally produced melanin pigmentation of the corneal epithelium.

Melanin pigmentation of the corneal epithelium was induced in pigmented guinea pigs by the topical application of colchicine to their eyes or by corneal cauterization with silver nitrate. With colchicine the pigmentation was preceded by the development of an abnormal corneal epithelium in which numerous cells became arrested in cell division. The corneal melanosis resulted largely from the migration of melanocytes into the corneal epithelium from the normally pigmented contiguous conjunctiva and to a lesser extent from the presence of melanin granules within corneal epithelial cells. In both models a leukocytic and vascular invasion of the cornea proceded and accompanied the migration of melanocytes into the corneal epithelium. Electron microscopy disclosed cells with the same morphology as conjunctival melanocytes between the epithelial cells of the cornea. Mature melanin granules were also present within some squamous epithelial cells as individual granules or as clusters. The ultrastructural findings are viewed in relation to how melanin granules are transferred from melanocytes to epithelial cells. Evidence is presented which suggests that malanin granule transfer may follow the fusion of the membranes of the melanocytes and epithelial cells.


Goiter formation following prostaglandin administration in rats.

Prostaglandins (PGE1 and PGE2) induced a hyperplastic microfollicular goiter with a high radioiodine (131I) thyroid uptake, increased endocytosis, a heavy autoradiographic (125I) reaction, and a moderate increase of thyroid hormones (T4, T3), thyroxine-binding globulin (TGB), and thyrotropin (TSH) concentrations in adult rats. Ultrastructurally, both prostaglandins (E1 and E2) markedly stimulated the thyroid cell activity and increased the number of pseudopodia, the size of colloid and dense granule populations, and the number of polysomes. Conversely, a hypofunction of thyroid glands with low radioiodine (131I) thyroid uptake, a decreased autoradiographic (125I) reaction, and a moderate decrease in T4, T3, TGB, and TSH concentrations were observed following prostaglandin F 2alpha. Ultrastructurally, a decrease in size of the colloid and dense granule population and the number of degenerative mitochondria occurred infollicular cells. An intense hyperplasia of parafollicular (C) cells, with abundant population of characteristic dense granules, could be seen in PGF 2alpha-treated rats. A marked decrease of radioiodine (131I) uptake, endocytosis, and autoradiographic (125I) reaction and a sharp decline in T4, T3, and TBG were observed in hypophysectomized and chronically prostaglandin-treated rats. Light and electron microscopy revealed signs of an advanced thyroid hypofunction with flat cuboidal cells, reduced microvilli, scarce endoplasmic reticulum, and few dense droplets. The present findings demonstrate that the chronic administration of prostaglandins exerts significant effects of thyroid gland and goiter formation (goitrogenesis), radioiodine metabolism, and hormone synthesis, and that these effects are mediated by TSH secretion.


Reticular cell hyperplasia and amyloidosis in a line of mice with low leukocyte counts.

Two pathologic conditions, reticular cell hyperplasia and amyloidosis, were studied in a strain of mice selectively bred for low leukocyte counts (LLC). At the age of 3 to 6 months, 70% of the mice developed reticular cell hyperplasia in the inguinea lymph nodes, and at 11 to 18 months, about 100% of them developed amyloidosis in the spleen and in the kidney, liver, and adrenal glands. Immunofluorescence was revealed in the glomeruli, interstitium of the tubules, and the amyloid skeleton of the papilla when the kidney sections were incubated with fluorescein-labeled antimouse immunoglobulins. Both intracellular and extracellular amyloid fibrils were found in the liver, spleen, and kidney sections by electron microscopy. Distended rough endoplasmic reticulum (RER) cisternae and hypertrophy of RER with or without the simultaneous presence of amyloid fibrils in the reticular cells of the spleen and Kupffer cells of the liver were observed. In this light, we believe that the pathologic conditions are manifestations of immunologic events that are characteristic of the LLC mice with immune deficiency or abnormality in the immune system. We conclude that the origin of amyloid protein is at the RER. We discuss processes of amyloid fibril formation and some genetic aspects of amyloid development.


Histopathology of spontaneous regression in virus-induced murine leukemia.

The histopathology of the spontaneous regression of murine leukemia induced by a particular strain of Friend leukemia virus was studied in Swiss ICR/Ha mice. Animals inoculated with the regressing strain of Friend virus exhibited an initial pathologic response identical to that induced by conventional strains of Friend virus. Unlike the fatal leukemia produced by conventional Friend virus, the pathology of the disease induced by the regressing strain of Friend virus appeared to be self-limiting. The histopathology of the two diseases is compared in this report.


Striated membranous structures in human hearts. An ultrastructural study.

Straited membranous structures (SMS), which consisted of sheets or ribbons of 130 to 220 A in thickness, showed variable patterns of periodic substructure, and resembled SMS described in renal and ocular tissues in various diseases, were found in extracellular locations in a) mitral valve (2 patients) and tricuspid valve (1 patient) of 2 patients with mitral valvular prolapse, b) mitral valve and femoral artery of 1 patient with Marfan's syndrome and prolapsed mitral valve, and c) myocardium (2 patients) and thickened endocardium (3 patients) of 3 patients with congenital heart disease associated with muscular obstruction to right ventricular outflow. Striated membranous structures measured up to several microns in diameter, often were highly folded and convoluted, and sometimes appeared circular in outline. Some SMS measured from 130 to 150 A in thickness and had indistinct edges and poorly defined periodicity. The majority of SMS, however, had greater thicknesses, in the range of 200 A, and a periodicity characterized by alternating light and dark bands with a spacing that varied from 100 to 160 A. The structures were associated with thickened basement membranes, elastic fibers, and membrane-bound bodies of the type thought to be involved in elastogenesis. Evidence available suggests that SMS results from an unusual pattern of arrangement of a component, possibly Type IV collagen, of basement membrane material.


The morphologic similarities of human and canine globoid leukodystrophy. Thin section and freeze-fracture studies.

Human and canine globoid leukodystrophy are shown to be indistinguishable morphologically. Both have characteristic deposits with polygonal cross-sectional profiles in addition to twisted ribbon-like structures. The specificity of the deposits is emphasized, and their laminated nature is corroborated by the freeze-fracture studies. Their apparently hollow profiles in cross section are thought to be produced by the tight arrangement of the bilayers that prevent penetration of the stain.


Effect of dehydration on stimulation of ADH release by heterologous renin infusions in conscious dogs.

Unanesthetized dogs were infused with heterologous (hog) renin at 0.33 Goldblatt U/kg per h for 2 h, once normally hydrated and once after 48 h of dehydration. Dehydration increased the average plasma osmolality from 306 to 322 mosmol/kg, the plasma renin activity (PRA) from 0.5 to 1.4 ng/ml per h, and the plasma antidiuretic hormone (ADH) concentration from 1.7 to 3.7 muU/ml, although the latter was not statistically significant. Renin infusion resulted in approximately the same average PRA, about 10 ng/ml per h, in both states of hydration. Mean arterial blood pressure increased during renin infusion in both states of hydration, although the increase was greater when the dogs were normally hydrated. There was no apparent effect of renin infusion on plasma ADH concentration when the dogs were normally hydrated, but in the dehydrated state renin infusion was accompanied by an increase from 3.7 to 6.3 muU/ml in plasma ADH concentrations after 80 min of infusion. There were no apparent changes in plasma osmolality or sodium or potassium concentrations due to the renin infusions; however, plasma osmolality and potassium concentration decreased during the course of the experiment. The results suggest a possible role for the renin-angiotensin system of renin released by the kidney in the control of ADH during dehydration. The metabolic clearance rate of the hog renin was 37 ml/min-kg.


Canine gut receptors mediating pancreatic responses to luminal L-amino acids.

Pancreatic protein and bicarbonate outputs were measured in dogs with pancreatic fistulas receiving intravenous secretin while individual L-amino acids or mixtures of L-amino acids were perfused into proximal intestine, Both phenylalanine and tryptophan were potent stimuli of pancreatic secretion; alanine, leucine, and valine increased protein outputs but their effects were small and not statistically significant. Six other amino acids were ineffective. Tryptophan perfused together with phenylalanine augmented responses to phenylalanine; methionine, ineffective when perfused alone, did not alter responses to phenylalanine when perfused with the latter. Responses to phenylalanine perfused at concentrations above 8 mM were dependent on load and were mediated by lengths of proximal bowel greater than 10 cm.


Canine pancreatic response to intestinally perfused oligopeptides.

Although older work indicated that luminal peptides are stimulants of pancreatic secretion, these earlier experiments were performed with crude peptide mixtures containing amino acids that are also known stimulants. Furthermore, no information was provided about size or composition of stimulating peptides. For this reason, the problem was reinvestigated with commercially synthesized oligopeptides in dogs equipped with chronic gastric and pancreatic fistulas. Synthetic peptides at 30 mM concentrations were perfused into the proximal bowel when luminal pancreatic proteases were reduced to undetectable concentrations and dogs were receiving intravenous exogenous secretin infusions. Increases in pancreatic outputs of protein and bicarbonate were measured. Of the peptides tested, only glycylphenylalanine, glycyltryptophan, and phenylalanylglycine stimulated, whereas both di- and triglycine were without effect. It was concluded that some, but not all, oligopeptides in the gut lumen are stimulants of pancreatic secretion.


Canine pancreatic responses to intestinally perfused proteins and protein digests.

Pancreatic bicarbonate and protein secretory responses to intestinally perfused proteins or digests of proteins were measured in dogs with chronic gastric and pancreatic fistulas when luminalpancreatic protease concentrations were reduced to undetectable levels. Protein digests were analyzed for amino acid content, and various other indirect met-ods were used to assess the composition of the digest mixtures. Of five undigested proteins, none evoked more pancreatic secretion than a control perfusion with saline. Peptic digestion of these same proteins converted four of them to polypeptides that were poten stimuli of a pancreatic juice similar in HCO3-/protein ratios to that evoked by luminal amino acids. Dialyzed peptic digests of one of the proteins, bovine serum albumin (BSA), retained potency. Likewise, digestion of BSA with endogenous or exogenous pancreatic proteases converted the protein to a stimulus about equipotent with the peptic digest, though the composition of the pancreatic digests differed markedly from that of the peptic digests. We conclude that a) luminal peptides of four or more amino acids can stimulate the pancreas and b) during protein alimentation a wide array of luminal protein products may evoke pancreatic secretion.


Adrenergic receptors mediating depolarization in brown adipose tissue.

Adrenergic receptors mediating depolarization in in vitro neonatal rat brown adipose tissue (BAT) have been characterized by use of adrenergic agonists and antagonists. Releasable endogenous catecholamine was present in BAT as demonstrated by tyramine- and 1,1-dimethyl-4-phenylpiperazinium iodide- (DMPP) induced depolarization in BAT from normal rats and its absence when BAT from reserpinized rats was used. In BAT from reserpinized rats l-norepinephrine, l-phenylephrine, and l-isoproterenol all similarly depolarized the bronw adipocytes over the concentration range of 10(-8) to 10(-6) M with a maximal depolarization of about 25 mV. Dopamine and d-norepinephrine were more than 100 times less potent. The beta-adrenergic blocker propranolol competitively inhibited isoproterenol-induced depolarization, whereas the alpha-adrenergic blackers, phentolamine and phenoxybenzamine, inhibited the phenylephrine-induced depolarization with much smaller inhibitory effects on the isoproterenol-induced depolarization. Both phenylephrine and isoproterenol elicited transient depolarizations when briefly added to the bathing medium while continuously recording from the same cell. Both the agonist and antagonist studies are interpreted as indicating the presence of both alpha- and beta-adrenergic receptors on BAT cells which mediate catecholamine-induced depolarization.


Mechanisms of temperature regulation in heat-acclimated hamsters.

Mechanisms of temperature regulation were assessed by measurements of oxygen consumption (VO2), body temperature (Rre = rectal, Tsk = skin), evaporative water loss (EWL), regional distribution of blood flow, and blood volume. Hamsters (Mesocricetus auratus) were acclimated to ambient temperatures of 34 or 22 degrees C. VO2 of 34 degrees C-exposed animals was reduced to 50% of that of controls at 22 degrees C, whereas EWL with heat exposure was almost double that of controls. Heat-acclimated animals had a slightly elevated Tre in comparison to 22 degrees C-acclimated animals, whereas there was a marked elevation in Tsk with heat exposure, in contrast to control animals at 22 degrees C. Blood flow distribution measurements indicated that with 34 degrees C exposure there was a decreased flow in liver, kidney, and intestine, whereas there was an increase to the carcass. Red cell and plasma volumes in heat-acclimated hamsters were decreased belwo the values of the 22 degrees C controls. Heat acclimation of the fhamster appears to involve reduced VO2 and increased WEL. Convective and radiative heat loss appear to be maintained by increased Tsk with heat exposure. Nonevaporative heat dissipation mechanisms are of primary importance in thermoregulation of the heat-acclimated hamster, and it is suggested that this is mediated by increased peripheral blood flow with reduced flow to the viscera.


Inhibition of proximal tubular hydrolysis and reabsorption of bradykinin by peptides.

[3H] bradykinin ([3H] BKN) was microinfused alone or in the presence of a 390- or 780-fold excess of BKN or angiotensin I (AI) into proximal tubules in Inactin-anesthetized rats. Urinary excretion of 3H-labeled material was measured, and intact peptide and its metabolites were identified and quantified. When [3H] BKN was administered with BKN or AI, urinary recovery of 3H-labeled material was increased in a manner directly proportional to tubular length, suggesting that reabsorption of [3H] BKN is related to extent of tubular contact. BKN and AI were equally effective in inhibiting the reabosroption of [3H] BKN and its metabolites from proximal tubular fluid. In contrast, BKN but not AI effectively inhibited the enzymatic hydrolysis of [3H] BKN in the proximal tubule, The data suggest that the proximal tubular mechanism for reabsorbing BKN and its metabolites is of high capacity but not high specificity and that the mechanisms for enzymatic cleavage and reabsorption of BKN and its metabolites may had different specificites and capacities.


Glucose and bicarbonate reabsorption in edematous dogs.

Glucose and bicarbonate reabsorption were studied in dogs made edematour by aortocaval fistula (A-V dogs) and in sham-operated dogs. Following construction of the A-V fistula, there was a significant increase in body weight; glomerular filtration rate, renal plasma flow, hematocrit, and sodium excretion decreased significantly. Bicarbonate reabosorption was significantly higher in A-V than in sham dogs both during control and volume expansion. Volume expansion depressed bicarbonate reabsorption significantly in both groups. Glucose reabsorption fell following volume expansion in both groups; glucose reabsorption was significantly higher in A-V dogs than in sham dogs during control and volume expansion. Volume expansion led to a minimal increase in sodium excretion in A-V dogs when compared to the increase in the sham dogs. These data demonsttate that chronic sodium retention is associated with enhanced reabsorption of glucose and bicarbonate. The site in the neophron responsible for the increase in reabsorption of these substances cannot be determined with certainty based on these clearance studies although it is possible that proximal reabsorption may be enhanced in this model.


Effect of prostaglandin E2 on ovine maternal placental blood flow.

The effect of PGE2 on regional blood flows in the chronically catheterized near-term pregnant sheep was investigated using radioactive microspheres. The injection of 20 mug PGE2 per kilogram into the left ventricle of eight sheep resulted in no change in maternal brain and noncotyledonary uterine flow. The renal blood flow increased from 692 to 892 ml/min (P less than 0.004). The uterine blood flow decreased from 673 to 317 ml/min (P less than 0.001). The trium was bypassed by injecting 7 mug PGE2 per kilogram of sheep into a fetal venous catheter and permitting it to reach the placental vasculature after placental transfer. Eleven sets of observations were made in eight animals. We observed no change in the intrauterine pressure, maternal brain flow, and noncotyledonary uterine blood flow secondary to this procedure. The maternal renal blood flow changed from 592 to 669 ml/min (P less than 0.007). The uterine blood flow increased from 762 to 853 ml/min (P less than 0.02). The uterine vascular resistance decreased from 0.124 to 0.115 mmHg x min/ml (P less than 0.04). It was concluded that 1) PGE3 crosses the placenta quite readily, and 2) PGE3 causes dilatation of the maternal placental vascular bed.


D-Glucose enhancement of water reabsorption in proximal tubule of the rat kidney.

Water reabsorption in the proximal convoluted tubule of the rat kidney was examined by in vivo microperfusion techniques in order to examine the effect of D-glucose within the tubular lumen. When tubules were perfused with a balanced artificial solution containing Na, K, Cl, HCO3, urea, and D-glucose, absolute reabsorption averaged 4.01 +/- 0.24 nl/min per mm. Addition of D-glucose to the NaCl perfusate enhanced water reabsorption to values similar to those obtained with the balanced artificial perfusate. The enhanced water reabsorption consequent to the addition of D-glucose to the NaCl perfusion solution was completely inhibited by addition of phloridzin to the perfusate. The addition of an unabsorbed hexose, 2-deoxy-D-glucose, to the NaCl perfusate failed to enhance water reabsorption, whereas the addition of an incompletely reabsorbed sugar that is not metabolized, 3-O-methyl-D-glucose, resulted in partial enhancement of theabsolute rate of water reabsorption. These studies demonstrate that D-glucose has the specific effect of augmenting water reabsorption in the proximal tubule of the rat kidney.


Cat heart acetylcholine: structural proof and distribution.

The distribution of acetylcholine (ACh) in the cat heart was investigated by a pyrolysis-gas chromatography (PGC) method. The hearts were dissected into various regions and homogenized in acetonitrile in the presence of propionylcholine, internal standard. Following extraction with toluene and hexane, the choline esters were precipitated as the enneaiodide complex. The isolated choline esters were analyzed by PGC, and the peak corresponding to ACh was quantified. The compound extracted from heart tissue that eluted with the retention time of authentic ACh was identified by mass spectrometry as dimethylaminoethylacetate, the pyrolysis product of ACh. ACh concentrations were found to be higher in the atria than the ventricles. In both the atria and the ventricles, a higher content of ACh was found in the right than the left portions: right ventricle, 5.0 compared to left ventricle, 2.0 nmol/g; and right atrium, 16.8 compared to left atrium, 11.3 nmol/g. Some cats were subjected to a bilateral cervical vagotomy 3 wk before removal and analysis of heart tissue. Hearts from vagotomized cats contained less ACh than controls in the right ventricle (-31%), right atrium (-54%), SA node (-42%), and papillary muscle (-53%), but no decreases were found in the left ventricle, left atrium, or interventricular septum.


Ascending pressor and depressor pathways in the cat spinal cord.

Blood pressure responses to stimulation of the cervical dorsolateral sulcus (DLS) of the spinal cord and lumbar dorsal roots were studied in anesthetized, vagotomized, and paralyzed cats. Stimulation of the lumbar dorsal roots elicited pressor responses with high-frequency stimulation (50 Hz, 10 V, 1 ms) and depressor responses with low-grequency stimulation (1 Hz, 10 V, 1 ms). Pressor responses were converted to depressor responses after bilateral lesions were made in the DLS area rostral to the site of stimulation. These results suggest that the ascending spinal pressor pathways are localized in the DLS region. Furthermore, these depressor responses were abolished by placing additional bilateral lesions in the dorsolateral funiculus (DLF) rostral to the site of stimulation. These data indicate the presence of ascending depressor pathways in the DLF which are anatomically separate from pressor pathways. Both pathways were found to be bilateral systems, and decussation of fibers appears to be complete within three segments rostral to their entry into the spinal cord. Ascending depressor pathways have a low optimal frequency of activation, as opposed to the ascending pressor pathways which have a relatively high optimal frequency of activation. Neurophysiological evidence obtained by recording unit activity from the cervical sympathetic trunk confirmed the localization of the ascending pressor and depressor pathways.


Effect of histamine on intestinal fluid secretion in the dog.

Intra-arterial infusion of histamine into the small intestine caused about a onefold increase of blood flow, edema of the intestinal tissues and mesentery, and produced a copious secretion of fluid. The jejunal secretions had an ionic composition similar to that of plasma, whereas ileal secretions contained high concentrations of HCO3 with relative low concentrations of Cl. The secretions contained protein (1.5 +/- .2 g/100 ml, range 0.5-2.4) with a similar electrophoretic pattern of plasma protein. When lissamine green was present in the blood, it also appeared in the secretion to a considerable concentration. It is inferred from these findings that a major mechanism of fluid secretion by the action of histamine involves a filtration process across the mucosal epithelium by the incrreased tissue fluid pressure due to extensive capillary leak.


Changes in CNS responsiveness during hibernation.

The ability of the midbrain reticular formation (MRF) to produce thermogenic responses and to trigger arousal from hibernation was tested during successive quarters of individual hibernation bouts. Golden-mantled ground squirrels (Citellus lateralis) were implanted with bilateral cannula guides into the MRF. Single, bilateral, 1-mul injections of acetylcholine (ACh) at concentrations of 50, 100, or 200 mug/mul were delivered in each quarter of the same bout or in selected quarters of different bouts. The results show that the magnitude of thermogenic responses evoked by ACh stimulation of the MRF was depressed during the early portion of the bout and increased as time in the bout elapsed. Furthermore, the magnitude of responses evoked during hibernation was depressed in comparison to those evoked during euthermia, indicating the influence of inhibition on the responsiveness of the CNS during hibernation. We suggest that during hibernation, a progressive change in responsiveness of the CNS, perhpas focused in the MRF, controls the duration of each hibernation bout.


Correlation of plasma corticosterone levels with running activity in the blinded rat.

Blinded female reats were placed in running-wheel cages to monitor the phase of their activity cycle. After approximately a month of adaptation to the wheels, jugular vein blood samples were withdrawn at the beginning and end of the running phase of activity and analyzed for plasma corticosterone. By the time blood samples were obtained, the blined rats' activity cycles had desynchronized from the lighting cycle of the room in an apparently free-running fashion, and were out of phase with each other. The corticosterone levels were high at the beginning of the running phase and low at the end: begin run corticosterone was 34.5 +/- 13, end run corticosteronewas 14.2 +/- 10 (mean +/-SD in mug/100 ml of plasma; t = 7.93, df = 82, P less than 0.001). It was concluded that blinded rats do have an adrenocortical rhythm and that it is in phase with the activity cycle of each individual rat.


Early postglomerular plasma concentrations of chloride, sodium, and inulin in the rat kidney.

Sodium, chloride, and inulin concentrations were measured in plasma collected from the terminal portions of long efferent vessels at the subcapsular surface of the rat kidney. Sodium concentration equaled and the concentrations of chloride and inulin were less than those in peripheral plasma. During benzolamide infusion, chloride concentration equaled while inulin concentration remained less than in peripheral plasma. In free-flow micropuncture samples collected randomly during control conditions, chloride concentration rose rapidly in the early proximal tubule and then remained elevated and constant throughout the remainder of the proximal tubule accessible to micropuncture. These experiments indicate that normally tubular reabsorbate low in chloride and inulin is added to the blood traversing the early postglomerular vessels before reaching the kidney surface. Bases on the analyses of proximal tubular fluid, this type of reabsorbate appears available only from the early proximal tubular segment. We conclude that a close functional relationship exists between the first segment of the proximal tubule and the early postglomerular blood supply characteristic of the superficial cortical nephron.


Development of the renal response to blood volume expansion in normal and fast-growing rats.

Male rats from reduced (fast-growing) litters between 14 and 50 days of age were studied. Standard renal clearnce techniques were employed. After a 60-min control period, the animals were infused (2.3% body wt) with heparinized donor blood obtained from lillermates of the same age. Renal function was followed for an additional 60 min. The efficiency of the diuretic response, the percent infused volume excreted above control levels, and the sodium efficiency, the percent infused Na excreted, were calculated. Results indicate that both efficiencies develop in a discontinuous pattern and that they are comparable. This pattern of development, as well as the magnitude of the mature response, is comparable to that previously reported for rats from intact (normally growing) litters. The onset and attainment of the mature response is, however, shifted in time, such that reduced-litter animals achieve the mature response 10-15 days earlier than intact-litter rats. Results exclude chronological age or body weight alone as principal determinant of the mature response and suggest that some function of growth rate is responsible for the maturation of this regulatory function.


Effect of rapid temperature change on mean body temperature and gill ventilation in carp.

Carp were transferred from 25 degrees C water to a calorimeter at 15 degrees C or from 15 degrees C water to a calorimeter at 25 degrees C. During cooling, dorsal muscle temperature (Tdm) and mean body temperature (Tb) were continuously monitored. During the first minutes Tb changed rapidly, while Tdm changed only slightly. In a 0.468-dg fish, Tdm decreased to two-thirds of the final value in 8.05 min, while Tb attained this value in 3.6 min. Tdm changed faster during heating than during cooling. Carp were also placed in a device where gill ventilation (VG) could be continuously monitored while rapid shifts in the temperature of the inspired water (TPINSP) AND/OR BODY SURFACE (Tbs) were effected. Changing Tinsp and Tbs both effected rate-sensitive changes in VG, although Tinsp was more effective. Decreases in Tinsp or Tbs produced decreases in VG; increases in Tinsp or Tbs had an opposite effect. The fish respiratory system is sensitive to the rate of change of external temperature. This sensitivity provides evidence for the existence of peripheral thermal input to the systems regulating respiration in teleost fish.


Sex and estrogens in protection against circulatory stress reactions.

From Wistar rats, data are presented which indicate that inbred females a) have a greater ability to clear particulate matter from the blood stream than do males of the same strain; b) are significantly more resistant to two different forms of lethal circulatory stress (e.g., intestinal ischemia and whole-body trauma) than are males; and c) exhibit a greater resistance to undergo reticuloendothelial system (RES) phagocytic depression after both forms of lethal trauma than do males. Estradiol treatment of males, using either acute, massive (1 or 10 mg/kg) or multiple, low dose (10 or 100 mug/kg) regimens, confers trauma resistance on such animals. Such estradiol treated male rats exhibit hyperactive RES's. These estradiol-treated males, when subjected to either lethal ischemia or trauma, fail to demonstrate the early RES phagocytic depression seen in untreated controls. Untreated female as well as estradiol-treated male rats exhibit significantly higher arterial blood pressures post-trauma than do untreated male rats. Direct microscopic observation of rat mesenteries indicr whole-b0dy trauma, the untreated females as well as the estradiol-treated males exhibit significantly less dilatation of microscopic capacitance vessels (i.e., venules) than do untreated male rats. The data reported herein could be used to suggest that estrogenic hormones may play pivotal roles in a) the amelioration of an organism's reaction to systemic stress; and b) control of macrophage and peripheral vascular functions.


Osmoltye and tryptophan receptors controlling gastric emptying in the dog.

The effect of three monosaccharides, three disaccharides, two dipeptides, combinations of tryptophan with two hexoses, one hexitol, and two amino acids ongastric emptying was studied in dogs to further define the samll intestinal receptors responsive to osmolytes and tryptophan. On a molar basis the disacchardies and dipeptides were almost twice as potent as their respective constituent monosaccharides or amino acids implying that the osmoreceptor is deep to the brush border disaccharidases and cytosol dipeptidases. Tryptophan probably acts by a mechanism different from the osmoreceptor since slowing of gastric emptying by tryptophan was inhibited by methionine which has no effect on a stimulant of the osmoreceptor mechanism. Lysine unlike methionine does not share the neutral amino acid transport pathway with tryptophan. Lysine did not change the inhibitory effect of tryptophan on gastric emptying. This imples that transport of tryptophan into the intestinal cell is necessary for its slowing effect. Glucose and galactose also inhibited the tryptophan effect whereas a nonabsorbed hexitor, mannitol, was without effect. Interference by the hexoses was also probably by competition with tryptophan for transport into the cell. These studies further indicate that the tryptophan receptor is different from the osmoreceptor.