In vitro bioassay of LH in human serum: the rat interstitial cell testosterone (RICT) assay. A sensitive bioassay for serum LH and hCG has been developed by utilization of the testosterone response of collagenase-dispersed rat Leydig cells to gonadotropic stimulation in vitro. Testosterone production by dispersed interstitial cells is stimulated by human, ovine, bovine, porcine, rat and rabbit LH, and by hCG and pregnant mare serum gonadotropin. The rat testis interstitial cell assay gives parallel dose-response curves for all steroidogenic gonadotropins tested, and thus permits cross-species comparison of the intrinsic biological activities of native and modified gonadotropins. The sensitivity of the rat interstitial cell bioassay is equal to or higher than that of radioimmunoassay, with detection limits of 50 muU for hMG and 20 muU for hCG. The optimum conditions for bioassay of serum gonadotropins were provided by incubation of dispersed interstitial cells in the presence of 1-methyl 3-isobutyl xanthine with the addition of gonadotropin-free serum or 5% BSA to ensure a constant proportion of serum protein in all assay samples and standards. Assays performed under these conditions gave parallel dose-response curves and identical maximum responses to both standards and serum samples containing endogenous LH or hCG. All responses to human gonadotropin standards and serum samples in the bioassay were abolished by incubation in the presence of antisera to LH or hCG. This sensitive and specific method permits bioassay of basal levels of LH in male and female serum, and of the higher gonadotropin levels in postmenopausal and pregnant subjects after appropriate dilution of the serum samples. For normal men and women, serum samples of 25-100 mul are employed, while volumes of 1-20 mul are adequate for assay of LH in postmenopausal or hypogonadal subjects. Serum LH values in hypopituitary and oral contraceptive-treated subjects were usually undetectable, while LH levels in normal subjects were always measurable with good precision. The within-assay coefficient of variation for measurement of a normal male plasma pool (30 mU/ml) was +/- 10%, and the between-assay variation was +/- 15%. The precision of the assay (lambda) was 0.035 +/- 0.015 (n = 72). In 42 normal females, the bio: immuno (B:I) ratio for serum LH was 1.20 +/- 0.40 (SD), and no consistent change in ratio was observed throughout the menstrual cycle. By contrast, significantly higher B:I ratios were observed in normal males (2.5 +/- 0.4), postmenopausal females (2.6 +/- 0.6) and patients with Turner's syndrome (2.6 +/- 0.6). These findings suggest that the LH circulating in normal female plasma is similar in biological and immunological activity to hMG, whereas the LH present in normal male plasma and in states of increased gonadotropin secretion has a relatively higher biological activity. The rat interstitial cell bioassay provides for the first time a practical and precise assay for measurement of the biologically active LH levels in serum of normal biologically active LH levels in serum of normal human subjects.


A comparison of plasma TSH levels in patients with diffuse and nodular non-toxic goiter. Plasma TSH levels were measured in 115 euthyroid patients with simple goiter, of whom 52 had diffuse and 63 nodular enlargement of the thyroid gland, and in 191 euthyroid patients without goiter. There was no significant difference between the plasma TSH levels in the patients with diffuse goiter and the non-goitrous controls, implying that the maintenance of diffuse hyperplasia is not dependent upon a raised level of plasma TSH. On the other hand, plasma TSH levels in the patients with nodular goiter were significantly lower than those recorded in either the patients with diffuse goiter (P less than 0.01) or in the patients without goiter (P less than 0.0001), supporting the view that thyroid function may be autonomous in nodular goiters.


Circannual cycle in plasma testosterone levels in man. In a groups of 15 healthy male subjects a statistically significant circannual cycle in plasma testosterone levels was assessed by sampling blood at 3-monthly  intervals. Peak levels were found in summer and early autumn and a nadir in the winter and early spring.


Amniotic fluid reactivity detected by somatomedin C radioreceptor assay: correlation with growth hormone, prolactin and fetal renal maturation. Amniotic fluid was assayed by a radioreceptor assay utilizing 125I-somatomedin C and placental membranes. Growth hormone and prolactin levels were measured by radioimmunoassay at different gestational ages (8-41 weeks). Somatomedin receptor activity, growth hormone, and prolactin reached high levels during early gestation (8-26 weeks) displaying different patterns of appearance which reflect fetal serum levels of these hormones. After 26 weeks gestation all these hormones decreased in concentration. This decrease showed a strong correlation with fetal renal maturation as measured by amniotic fluid creatinine levels.


alpha and beta glycoprotein hormone subunits (hLH, hFSH, hCG) in the serum and pituitary of the human fetus. Utilizing specific radioimmunoassay and gel chromatographic separation methods, the concentration of a glycoprotein hormone subunit and the beta subunit of hCG, hLH, and hFSH was determined. The alpha glycoprotein hormone subunit is present throughout gestation in the serum and pituitary of the human fetus; little or no subunit is apparent in contrast to that of intact LH and FSH.


Three strains of influenza A virus (H3N2): interferon sensitivity in vitro and interferon production in volunteers. Three antigenic variants of the H3N2 subtype of wild-type influenza A virus (representing the years 1968, 1972, and 1974) were examined for their sensitivity to interferon and for their ability to induce local respiratory tract interferon in volunteers. In addition, the time of appearance of symptoms in infected volunteers was correlated with the patterns of virus shedding and interferon production. The sensitivity to interferon and the ability to stimulate nasopharyngeal interferon were similarly high for all three strains. Symptomatic illness, peak virus shedding, and peak interferon response all occurred within a 26-h period. These findings imply that interferon or its inducers theoretically could be protective if applied prophylactically, but would be less efficacious when used therapeutically.


Blood culture technique based on centrifugation: clinical evaluation. A total of 1,000 blood samples from patients suspected of having a bacteremia were analyzed concurrently, where possible, by three methods: (i) Trypticase soy broth with sodium polyanethol sulfonate and a CO2 atmosphere: (ii) pour plates with either brain heart infusion agar or Sabouraud dextrose agar; and (iii) centrifugation of the suspected organism in a hypertonic solution. There were 176 positive cultures. The centrifugation technique recovered 73% of the positive cultures. The broth and pour plate techniques recovered 38 and 49%, respectively. The centrifugation technique showed an increased isolation rate for Pseudomonas, fungi, and gram-positive cocci. In general, for each organism the time required for the detection of a positive culture was shortest for the centrifugation technique.


Clinical comparison of aerobic, hypertonic, and anaerobic culture media for the radiometric detection of bacteremia. The BACTEC 225 was used to test 5,811 routine blood cultures over a 20-month period. Aerobic, anaerobic, and hypertonic media were employed. The BACTEC 225 detected 511 positive cultures; 407 of these were considered significant organisms, and 104 were presumed contaminants. Of the significant positive cultures, 15% were detected within the first 12 h of incubation, 52% within 24 h, 82% within 48 h and 92% within 72 h. Aerobic, anaerobic, and hypertonic media are recommended for each venipuncture since 56 cultures were isolated from the aerobic medium only, 110 from the anaerobic medium only, and 94 from the hypertonic medium only. There were 16 patients who had multiple venipunctures from which organisms were repeatedly isolated from only one medium: two from the aerobic medium, four from the anaerobic medium, and ten from the hypertonic medium only. Detection times were not significantly different for the aerobic and hypertonic media. However, there were five patients with multiple venipunctures in which growth was detected radiometrically at least 48 h earlier in the hypertonic than in the aerobic medium. False-positive growth index readings were noted in 1,085 (19%) of the aerobic vial, 11 (0.19%) of the anaerobic vials, microorganisms were isolated from at least one of the companion vials. Using 5% co2 to flush the aerobic vials. With some false-positive aerobic and hypertonic vials decreased the number of false positives to about 6% of the total.


Evaluation of the API 20 c microtube system for the identification of clinically important yeasts. The API 20 C microtube system containing 20 biochemical tests for the identification of yeasts was compared with conventional tests used in the Mayo Clinic mycology laboratory. Three hundred isolates of clinically important yeasts were studied, and agreement of the carbohydrate fermentation and assimilation tests between the systems was good. The API 20 C represents a useful, commercially available screening method for the identification of yeasts; however, it is not a complete system and must be used in conjunction with microscopic morphological features and, when appropriate, with other biochemical tests.


Anaerobic infections in children: a prospective survey. Over an 18-month period, cultures from 95 infants and children yielded 146 anaerobic organisms in 110 clinical specimens. Bacteroides was the most frequently isolated anaerobe, followed by Propionibacterium and Clostridium species. Intra-abdominal sources, soft tissues, and blood were the three major sources (82%) of isolation of anaerobes. Whereas most patients (58%) were over 5 years of age and only 11% were newborns, anaerobic infections constituted a rather uniform proportion of all infections, regardless of sources, in all age groups. Anaerobes accounted for only 2.9% of all positive cultures encountered from the various sources. Rates of recovery of anaerobes from intra-abdominal sources were significantly the highest, and from soft-tissue infections they were significantly the lowest. The anaerobic bacteremias observed were of no clinical significance when Propionibacterium species were isolated; however, recovery of other anaerobes from the blood, and primarily Bacteroides species, was usually associated with clinical disease. Except in blood cultures, anaerobes almost invariably coexisted with facultative bacteria.


Gingival flora of the dog with special reference to bacteria associated with bites. Gingival scrapings from dogs were examined to determine their aerobic bacterial flora. Of particular interest was the frequent recovery of three unclassified groups of aerobic gram-negative bacteria, IIj, EF-4, and M-5, previously associated with human dog-bite infections. Although no set pattern was found between the variability and consistency of gingival microbiota as related to age, sex, or breed of dog, a certain characteristic flora can be predicted in the healthy canine gingiva. Members of the following genera were found: Streptococcus, Staphylococcus, Actinomyces, Escherichia, Corynebacterium, Pasteurella, Caryophanon, Mycoplasma, Acinetobacter, Moraxella, Neisseria, Enterobacter, and Bacillus.


Inhibition of Bacteroides fragilis on blood agar plates and reversal of inhibition by added hemin. Bacteroides fragilis strains formed much smaller colonies on most types of blood agar plates than they did on the same media without blood. Blood inhibited strains of B. fragilis subsp. distasonis the most and B. fragilis subsp. fragilis the least. The inhibition could be eliminated by adding hemin to the blood agar. The inhibitory component of the blood was inside the erythrocytes and appeared to be the hemin-free globin of hemoglobin.


Inhibition of Streptococcus mutans strains by different mitis-salivarius agar preparations. Several Streptococcus mutans strains were markedly inhibited by mitis-salivarius agar manufactured by Baltimore Biological Laboratories, but little, if any, inhibition was noted using Difco Laboratories' mitis-salivarius agar. Supplementation of the basic medium with sucrose and bacitracin for specific selection of S. mutans resulted in suppression of representative S. mutans type a strains regardless of manufacturer.


Pitting of agar surface by Pseudomonas stutzeri. A strain of Pseudomonas stutzeri which exhibited pitting of agar surfaces is described.


Dependability of sensitivity tests in primary culture. Primary sensitivity tests were done on 90 specimens of infected urine, and the results were compared with those of secondary tests on pure cultures done by three diffusion methods. There was good correlation between the four methods. In a second study, the reliability of primary tests prepared in the clinical laboratory on specimens of pus was assessed, and the frequency with which a definitive result was obtained with different types of specimen was determined. Recommendations are made for the economic use of these tests.


Counter-immunoelectro-osmophoresis for the detection of infantile gastroenteritis virus (orbi-group) antigen and antibody. A moderatley sensitive, rapid, and economical test scheme for the detection of infantile gastroenteritis virus (IGV) in stool or antibody in serum has been developed and evaluated. The test scheme with minor modifications was an adaptation of a counter-immunoelectro-osmophoresis system we once used for the detection of hepatitis B antigen. Large numbers of stool samples may be screened during half a working day for the presence of IGV using reference antiserum to IGV prepared in guinea-pigs. Serological studies of a diagnostic but not epidemiological nature may also be performed with equal facility by this same test scheme using highly purified IGV antigen derived from stool.


A card test for the serodiagnosis of human leptospirosis. A macroscopic agglutination test for detecting leptospiral antibodies in human sera is described. The test utilizes a stained preparation of non-pathogenic leptospires and is performed on the Brewer diagnostic cards used for bovine brucellosis screening. The agglutination of the stained antigen is more easily observed than the current macroscopic slide test using unstained leptospiral antigens. The non-pathogenic serotype patoc is agglutinated by sera from humans infected with serotypes pomona, hardjo, ballum, and copenhageni with a sensitivity of 94% in comparison with the microscopic agglutination test.


Idiopathic non-syphilitic paroxysmal cold haemoglobinuria in children. Three examples of non-syphilitic paroxysmal cold haemoglobinuria (PCH) in children are described which occurred, within a period of 16 days, in association with a febrile illness. No definite viral aetiology or obvious epidemiological association could be established. A Donath-Landsteiner antibody of anti-P specificity was demonstrated in all three patients. The serological aspects of PCH are critically discussed.


Chemotaxis, random mobility, and mobilization of polymorphonuclear leucocytes in malnutrition. Neutrophil mobilization following administration of Pseudomonas polysaccharide was significantly reduced in malnutrition, especially during infection. The random mobility of polymorphonuclear leucocytes (PMNs) was slightly decreased in undernutrition. Chemotactic migration of PMNs was depressed and correlated more with the presence of infection than with nutritional deficiency. It is possible that these abnormalities of PMN mobilization and mobility in malnourished individuals contribute to suboptimal amount, kinetics, and pattern of tissue inflammatory response to bacteraemic challenge.


The 'septic spleen'--a critical evaluation. The relationship between the consistency of the spleen at necropsy and the presence of bacteria in that organ was examined in 192 consecutive necropsies. Also it was noted if the patient had received antibiotics just before death. An estimate of the number of neutrophils in the spleen was also made. No correlation could be found between any of these factors.


Liver-originating isoenzymes of alkaline phosphatase in the serum: a paraneoplastic manifestation of a malignant schwannoma of the sciatic nerve. A case of malignant schwannoma of the sciatic nerve is described associated with hepatic dysfunction in the absence of hepatic metastases. An elevated serum alkaline phosphatase activity was present with an isoenzyme pattern indicating hepatic involvement. These abnormalities disappeared after extirpation of the tumour. The patient is well, with no evidence of metastases, over two years later. It is concluded that the abnormality of serum alkaline phosphatase was induced by the tumour, and that the liver can be involved in the paraneoplastic syndrome.


Colonic lymphoid-glandular complex (microbursa): nature and morphology. A study of lymphoid-glandular complexes of the large bowel has been undertaken. Sections from 1924 surgical colectomy and proctocolectomy specimens were examined, and lymphoid-glandular complexes were observed in 231. It has been shown that they are distributed throughout the large bowel and occur in all age groups and in normal and disease states. An analogy has been drawn between them, the palatine tonsils, and the bursa of Fabricius. It is concluded that the lymphoid-glandular complex is, most probably, a normal structural entity of the large bowel and that it acts as a local receptor of antigenic material for future immune recognition. It is suggested that microbursa rather than lymphoid-glandular complex is more apt name for this structure.


Sputum cytology in two cases of Wegener's granulomatosis. Two patients with Wegener's granulomatosis are described in whom the sputum was found to contain abnormal cells, The diagnosis was suggested in the second case on cytological grounds alone. It is considered, therefore, that sputum cytology is a relevant investigation in the diagnosis of this condition.


A modification of Hepatest, using the Terasaki plate, for the detection of HBSAg in blood donors. A simple modification of Hepatest (Wellcome Reagents) is described, which lends itself to the rapid large-scale screening of blood donors. The technique uses 4 mul of HBSAb coated turkey cells (Cayzer et al., 1974), and Terasaki plates (Hopkins and Das, 1973), in contrast to the 25 mul used in the microtitre tray technique. This results in a considerable saving on the cost of reagents, the cost per test being reduced to 16% of the cost of the recommended method. In our hands, this modification is as convenient to use as the manual microtitre tray technique. Positive sera from the screen test are also tested for non-specificity using horse IgG coated turkey control cells. The falso positive screen test rate has been reduced by the adoption of a modified buffer containing turkey serum.


Projections of the locus coeruleus and adjacent pontine tegmentum in the cat. The projections of the locus coeruleus and adjacent pontine tegmentum have been studied using anatomical and physiological methods in the cat. Axonal trajectories were traced using either the Fink-Heimer I method following electrolytic lesions, or the autoradiographic method after injection of tritiated proline into the nucleus. Results with both methods were similar. Axons of locus noeruleus neurons ascended ipsilaterally through the mesencephalon lateral to the medial longitudinal fasiculus, ventrolateral to the central gray. In the caudal diencephalon, the ascending fibers entered the centrum medianum-parafascicular complex where they diverged into two fascicles: a dorsal fascicle which terminated in the intralaminar nuclei of the thalamus, and a ventral fascicle which gave off fibers to the ventrobasal complex and reticular nucleus of the thalamus while continuing centrolaterally into the lateral hypothalamus medial to the internal capsule. Fibers of the ventral fascicle ascended in the lateral hypothalamus and zona incerta and were traced through the preoptic region into the septum. Fibers could not be consistently traced to the cerebral cortex, and were not seen at all in the cerebellum. Throughout the ascending course of the path from the locus coeruleus, axons were given off to the pretectal area, the medial and lateral geniculate nuclei and the amygdala; fibers passed contralaterally through the posterior commissure, the midline thalamus, and the supraoptic commissure. Fibers descending from the locus coeruleus surrounded the intramedullary portion of the facial nerve and further caudally were observed ventrolateral to the hypoglossal and dorsal vagal nuclei. The axonal trajectories visualized with degeneration and autoradiographic methods followed closely those previously shown for reticular formation neurons, but were also similar to locus coeruleus projections revealed by histofluorescence methods. After injections of horseradish peroxidase into the centrum medianum-parafascicular complex, lateral hypothalamus or preoptic region, labeled neurons were located in the locus coeruleus, nucleus subcoeruleus, and lateral parabrachial nucleus. Reticular formation neurons were not labeled. Neurons in locus coeruleus and adjacent pontine tegmentum could be antidromically activated by stimulation in the rostral midbrain or caudal diencephalon. Our data indicate that both adrenergic and non-adrenergic neurons of the dorsolateral pontine tegmentum have similar projections.


Topological analysis of the brain stem of the axolotl Ambystoma mexicanum. The ventricular sulcal pattern and the cellular structure of the brain stem of the axolotl Ambystoma mexicanum have been studied in transversely cut Nissl and Bodian stained serial sections. Six longitudinal sulci, the sulcus medianus inferior, the sulcus intermedius ventralis, the sulcus limitans, the sulcus intermedius dorsalis, the sulcus medianus superior and the sulcus lateralis mesencephali could be distinguished. A seventh groove, the sulcus isthmi, clearly deviates from the overall longitudinal pattern of the other sulci. Although most neuronal perikarya are contained within a diffuse periventricular gray, 19 cell masses could be delineated; seven of these are primary efferent or motor nuclei, four are primary afferent or sensory centers, four nuclei are considered as components of the reticular formation, and the remaining four cell masses can be interpreted as "relay" nuclei. In order to study the zonal pattern of the brain stem, this structure was subjected to a topological analysis (cf, Nieuwenhuys, '74 and fig. 13). This analysis yielded the following results. In the rhombencephalon the grisea are arranged in four longitudinal zones which, following Kuhlenbeck, have been termed area ventralis, area intermedioventralis, area intermediodorsalis and area dorsalis. Where present the sulcus intermedius ventralis, the sulcus limitans and the sulcus intermedius dorsalis mark the boundaries between these four morphological entities. The zonal areas in question coincide largely, but not entirely, with the so-called functional columns of Herrick and Johnston. The most obvious incongruity is that the area intermediodorsalis contains, in addition to the nucleus fasciculi solitarii and the nucleus visceralis secundarius, two non-visceral sensory cell masses, namely the nucleus vestibularis magnocellularis and the nucleus cerebelli. The four morphological zones delineated in the rhombencephalon cannot be distinguished in the mesencephalon and it is of particular importance that the sulcus limitans does not extend into this part of the brain. Functionally, however, the medial part of the tegmentum mesencephali may be considered the rostral extreme of the somatic motor column, whereas the tectum primarily represents a somatic sensory correlation area.


The synaptic cluster (glomerulus) in the inferior olivary nucleus. This report describes the fine structural features and distribution of the synaptic cluster (glomerulus) within the inferior olivary nucleus of the opossum. The postsynaptic elements typically include spiny appendages and small diameter dendrites which exhibit attachment plaques and gap junctions. Profiles presynaptic to the central core of postsynaptic elements were differentiated on the basis of vesicle shape, vesicle size, as measured by a computer system, and junctional characteristics. Three categories of terminals with clear vesicles are present within the synaptic clusters in all nuclear divisions of the olive, whereas a fourth with large dense core vesicles is restricted primarily to the principal nucleus. The groups of pre and postsynaptic elements are surrounded by astrocytic lamellae and are most frequently encountered in the principal and rostral portions of the medial accessory nuclei. Possible identification of the sources of the synaptic components is discussed in relation to data available from Golgi impregnations, physiological reports and hodological evidence.


Auditory cortex in the grey squirrel: tonotopic organization and architectonic fields. The representation of sound frequency within auditory cortex has been investigated with microelectrode mapping techniques in grey squirrels. The cyto- and myeloarchitecture of mapped cortical surfaces was examined and related to recording data. Among the results were the following: (1) A primary field can be defined on the basis of both physiological and anatomical criteria.


Convergent thalamic and mesencephalic projections to the anterior medial cortex in the rat. Small microelectrophoretic deposits of horseradish-peroxidase (HRP) were placed at various loci within the gray matter of the rat's anterior medial cortex. A comparison of the patterns of retrograde cell-labeling charted in 26 such cases confirmed earlier findings in fiber-degeneration studies according to which the respective thalamocortical projections of the mediodorsal (MD) and anteromedial nucleus (AM) overlap each other over a wide region of the anterior medial cortex. This region of thalamocortical convergence, extending from pregenual levels caudalward as far as the anterior border of the retrosplenial cortex, corresponds almost exactly to the cortical region from which locally deposited HRP was found to be transported so as to label cells in one or both of two mesencephalic cell groups: the ventral tegmental area (AVT) dorsal and lateral to the interpeduncular nucleus, and the medial one-quarter of the pars compacta of the substantia nigra (SNC).


The olivocerebellar projection in the cat as studied with the method of retrograde axonal transport of horseradish peroxidase. II. The projection to the uvula. Following injections of small quantities of horseradish peroxidase (HRP) suspension in the uvula of the cat, the distribution of labeled cells in the inferior olive has been mapped. The findings confirm the conclusion made on the basis of studies of retrograde cell loss in the olive following ablations of the uvula (Brodal, '40b) that two small olivary subdivisions, the nucleus beta and the dorsomedial cell column project heavily to the uvula. In addition the HRP-study shows that the uvula receives a smaller number of fibers from two circumscribed areas of the contralateral medial accessory olive. These areas appear to project to the lateralmost parts of the uvula (fig. 4). The findings thus support the presence of a longitudinal zonal subdivision in the uvula. Labeled cells are found in the nucleus beta and the dorsomedial cell column also following injections of the fastigial nucleus and to a lesser degree of lobulus VII of the vermis (Hoddevik et al. 76). This may be due to collateral branching of olivary efferents. There is some evidence for a topographical correlation between dorsal and ventral parts of the uvula and rostral and caudal parts, respectively, of the nucleus beta and the dorsomedial cell column. This may be related to functional differences between the two parts of the uvula.


Retinogeniculate projections in albino and ocularly hypopigmented rats. The retinogeniculate fiber projections were studied by degeneration methods in several strains of rats with pigmentation in their eyes and pelts ranging from the intensely pigmented self phenotype to the albino. The ipsilateral retinogeniculate input in the self, Irish, and hooded rats, and rats with "bicolor fundus" is located medially within the dorsal alteral geniculate nucleus (LGd) and is seen as a single lamina of moderately dense degeneration.


Fiber analysis of the feline inferior cardiac sympathetic nerve. The left inferior cardiac nerves of nine adult cats were examined with the electron microscope. Electrical recordings were also made from four of these nerves. Most of the nerves contained between 25,000 and 40,000 unmyelinated fibers and 30 to 150 myelinated fibers. The diameters of the unmyelinated fibers ranged from 0.1 mu to 1.8 mu with mean diameters ranging from 0.47 to 0.78 mu in the various nerves. The myelinated fibers ranged in diameter from 1 mu to 9 mu with a mean difference of approximately 3 mu. Electrical recordings showed two peaks in both the C fiber and the Adelta fiber compound action potentials. Conduction velocities of the two C fiber peaks were approximately 0.7 and 0.9 m/sec. The two groups of A delta fibers had conduction velocities of approximately 7 and 16 m/sec.


Organization and development of brain stem auditory nuclei of the chicken: ontogeny of n. magnocellularis and n. laminaris. Nucleus magnocellularis (NM) and nucleus laminaris (NL) are, respectively, second- and third-order auditory nuclei in the chicken brain stem. In this report the morphogenesis of these nuclei is examined. The times of origin of the cells of these nuclei were studied with 3H-thymidine autoradiography. The number of cells in each nucleus and their rostro-caudal distribution within each nucleus was determined in Nissl-stained sections at 9, 11, 13, 15, 17, 19, and 21 days of incubation. For the above ages the volumes of NM and NL were also calculated planimetrically and the rostro-caudal distribution of volume within each nucleus was studied.


Pallidothalamic projections in the rat.

Pallidothalamic projections in the rat. The purpose of this investigation was to examine pallidofugal projections to the thalamus of the rat using a selective silver degeneration method and autoradiography. Degenerating pallidothalamic projections emerging from the anterior part of the pallidum formed two diffuse groups of fibers; one coursed ventromedially directly through the internal capsule without forming a lenticular fasciculus and terminated uniformly in the reticular, VA, VD, VM and the medial part of the VE. The otehr group coursed ventrolaterally in the internal capsule and, without forming an ansa lenticularis, entered the zona incerta, swept medially through and ventral to the medial lemniscus, and terminated in the medial part of the VE and throughout the VD.


Trans-glial channels in ventral nerve roots of crayfish. The sheath around the roots of the sixth abdominal ganglion in the ventral nerve cord of the crayfish consists of concentric layers of thin glial processes alternating with wide clefts containing filamentous connective tissue. Regions of each glial lamella are perforated by single, short, tubular channels: the trans-glial channels. In thin plastic sections examined in the electron microscope, the channels appear as slits that are 240 A wide and 450-550 A long which traverse glial lamellae less than 1,500 A thick. Branched tubular channels cross glial sheets that are thicker than 1,500 A. The thickest glial wrap is adaxonal; it closely encapsulates individual axons and its cell membrane is separated from the axolemma by a collagen-free space of only 150 A. The adaxonal glial cytoplasm contains unique, three-dimensional networks of interconnected tubules. Separate tubular lattices occur along these thicker processes. In replicas of freeze-fractured sheaths, the outer half of the plasma membrane belonging to the thin glial sheets exhibits many volcano-like protrusions which represent cross fractures through the necks of trans-glial channels. Corresponding depressions on the inner half of these membranes are sites where the plasma membrane invaginates to form the channels. Although some channels are randomly dispersed, others are lineraly positioned in restricted areas across successive glial layers. The number of channels is far more readily appreciated in replicas than in thin sections. The average frequency of channels is 16 per mu2 (range 8 to 33) in normal roots and does not differ significantly from the average of 13 per mu2 in proximal stumps of roots fixed three to four weeks after the roots were cut. The channels are not precisely aligned from one glial layer to the next but do appear to coincide approximately with the adaxonal tubular lattice. The combination of trans-glial channels and adaxonal tubular lattices may provide a complex conduit that could facilitate a rapid, passive flow of electrolytes and nutrients across the nerve sheath to the axonal surface. Horseradish peroxidase solutions bathing the ventral roots enter the trans-glial channels, extracellular clefts and finally the tubular lattices. This distribution supports the proposed role of the channels in a rapid extracellular passage of solutes. The channel profiles have a range of forms consistent with the supposition that they are not static but continually reforming. There are indications that, proximal to the cut, the areas of glial plasma membrane with channel profiles contain more junctional complexes between regenerating cells than between glial cells of normal sheaths. The channel profiles and aggregates of particles belonging to junctions are closely associated when they occupy the same region of the membrane.


Categories of axons in mammalian rami communicantes. The present study is an electron microscope analysis of the rami communicantes and its purpose is to determine the functional categories of unmyelinate axons in these nerves. Our findings indicate that the grey rami of segments T7, T8, or T9 in the cat consist of approximately 5,000 unmyelinated axons and 20 myelinated axons, and that these axons are post-ganglionic sympathetics. Although the numbers are new data, this conclusion confirms classic work. The white rami from the same segments contain approximately 3,200 unmyelinated axons and 1,600 myelinated axons. 80-90% of the myelinated axons are preganglionic sympathetics and the remainder are presumably sensory. This conclusion is also in confirmation of classic work. The new conclusions are that approximately 30% of the unmyelinated axons are preganglionic sympathetics, approximately 60% seem to be post-ganglionic sympathetics and the surprisingly small remainder may be sensory.


A re-examination of anatomical plasticity in the rat retina. Previous investigators have reported an increase in numbers of amacrine synapses in the inner plexiform layer (IPL) of the rat retina following light deprivation, and an increase in amacrine along with a decrease in bipolar synapses following light damage. Since there are several points of disagreement between the published reports on this subject we undertook a more detailed study of the effects of light deprivation and light damage on the retina. Four groups of eight male albino rat pups (14 days old) were raised for eight weeks under different conditions: (1) unsutured, bright light reared (UB); (2) bilaterally lid-sutured, bright light reared (SB); (3) unsutured, low light reared (UL); and (4) bilaterally lid-sutured, dark reared (SD). The intensity of the light given the UL group was equated with that striking the corneas of the SB group. Light microscopy showed that the retinas of the SB as well as the UB groups had almost complete degeneration of the outer retinal layers, indicating that even low intensity light, when continuous, causes severe retinal damage. The SD group was thicker in many of the retinal layers compared to the UL (control) group. Electron microscopy revealed that there were no significant changes in the incidences of any type of synapse in the IPL following light deprivation or light damage when averaged over total depth. This is in contradiction to the reports of other investigators. However, when the IPL was analyzed by levels, the incidence of amacrine-ganglion synapses was signficantly greater (p less than 0.05) in groups UB and SD, but only in the outer third of the IPL. Thus, extensive postnatal plasticity of IPL synapses in the rat retina did not occur under our experimental conditions. We found, at best, only limited effects which were confined to the amacrine-ganglion synapses.


Anatomical distribution of estrogen target cells in the avian CNS: a comparison with the mammalian CNS. The distribution of labeled cells was investigated in the brain of the ring dove one hour after administration of 3H-estradiol. Major areas of concentration of labeled cells were found in (1) the preoptico-strial region: nucleus preopticus medialis and nucleus interstitialis of the dorsal olfactory projection, (2) the basal hypothalamic region: nucleus hypothalamicus posterior medialis and nucleus inferior, (3) the amygdaloid region: nucleus taeniae and adjacent portions of the archistriatum, and (4) the midbrain: substantia grisea surrounding the nucleus mesencephalicus lateralis, pars dorsalis. The findings support the phylogenetic homologies between the avian nucleus interstitialis of the dorsal olfactory projection and the mammalian nucleus interstitialis of the stria terminalis, the avian nucleus hypothalamicus posterior medialis and the mammalian nucleus ventromedialis hypothalami, as well as the avian nucleus inferior and the mammalian nucleus infundibularis-premammillaris ventralis. The results also suggest that the nucleus medialis and other more differentiated labeled areas of the mammalian amygdala.


Scanning electron microscopy of the subarachnoid space in the dog. IV. Subarachnoid macrophages. Young dogs of both sexes were used in this study. Transmission and scanning electron microscopy were utilized for the examination of the spinal cord and choroid plexus with emphasis on the study of free cells. These procedures were modified so that, in certain cases, the same cells observed in scanning electron microscopy could be analyzed internally by transmission electron microscopy. One half of the animals were injected under anesthesia with horseradish peroxidase for observation of phagocytosis. This study confirms that the free cells observed in the subarachnoid space with the scanning and transmission electron microscopes are identical. The internal morphology of these cells corresponds to that of macrophages. This is further substantiated by the ability of these cells to localize horseradish peroxidase in discrete vacuoles within their cytoplasms. Both pial macrophages and epiplexus cells localize peroxidase in an identical manner in the same animal after one injection. In addition macrophages on the surface of the pia mater respond to extravasated red blood cells in a characteristic manner including phagocytosis. The plentiful population of macrophages on the surface of the pia mater supports the concept that these cells are of major importance in maintaining asepsis in the subarachnoid space.


Topographic organization of the projections from the entorhinal area to the hippocampal formation of the rat. The present study re-examines, with autoradiographic methods, the pattern of termination of fibers originating from various medio-lateral divisions of the entorhinal cortex on dentate granule cells and on hippocampal pyramidal cells of the rat. Entorhinal fibers were found to distribute in a proximo-distal gradient along the dendrites of dentate granule cells, with afferents from the medial entorhinal area terminating in the innermost portion of the entorhinal synaptic field, afferents from the lateral entorhinal area terminating in the most superficial portions of the entorhinal synaptic field, and intermediate medio-lateral locations in the entorhinal area terminating in intermediate locations in the entorhinal synaptic zone. A similar graded pattern of termination of medial and lateral entorhinal fibers was apparent in the very slight crossed projection of the entorhinal area to the contralateral dentate gyrus. In addition, a comparable gradient in the pattern of termination of entorhinal fibers was evident in the entorhinal projection field in the distal regions of the pyramidal cells of regio inferior of the hippocampus proper. Entorhinal projections to regio superior were, however, organized in quite a different fashion. In this zone, there was no evidence of a proximo-distal gradient in the patterns of termination of medial and lateral entorhinal areas along the dendrites of regio superior pyramidal cells. Rather, the medio-lateral organization was in a longitudinal dimension, with medial entorhinal afferents terminating in the portions of regio superior near the CA1-CA2 transition, and lateral entorhinal afferents terminating furthest from the CA1-CA2 transition, immediately adjacent to the CA1-subicular transition, and in the molecular layer of the subiculum proper. A comparable longitudinal organization of entorhinal projections to regio superior was also evident in the zones of termination of the crossed temporo-ammonic tract, contralateral to the injection. These results demonstrate a heretofore unrecognized complexity in the patterns of projection of the entorhinal area to the hippocampal formation, and illustrate that the entorhinal cortex cannot be divided into only two discrete divisions on the basis of the pattern of projection.


The retina and retinal projection on the lamina ganglionaris of the crayfish Pacifastacus leniusculus (Dana). The retinular cell morphology and ommatidia arrangement in the crayfish retina are studied. Each ommatidium contains eight receptor cells (R1-R8). Seven of them (R1-R7) contribute to a large spindle-shaped rhabdom with orthogonal layers of microvilli. Distal to the rhabdom of R1-R7, the 8th receptor cell forms a separate rhabdom with horizontal microvilli. The cell is four-lobed, is devoid of screening pigments, and forms a thin axon projecting past the first optic neuropile (lamina ganglionaris) and has a terminal in the second (medulla externa), indicating a separate function of the receptor. The axons from the eight receptors of one ommatidium project to different synaptic compartments (cartridges) in the lamina. A pattern is described where eight axons from three adjacent ommatidia join in one cartridge; and conversely, the axons from one ommatidium split and join to three cartridges. The seven axons from R1-R7 terminate in two levels of the lamina plexiform layer (epl 1 and epl 2), four in the distal and three in the proximal part. Among the monopolar ganglion cells, two types are found with lateral branches restricted to either of the two receptor terminal layers (M3 in epl 1 and M4 in epl 2) and axons terminating in the second optic neuropile. A correlation between the two orthogonal channels for e-vector discrimination and the two levels of terminals within the lamina is suggested. The retina is divided into dorsal and a ventral part with a mirror symmetry axis horizontally in the eye.


Synaptogenesis in the ventromedial hypothalamus of the prenatal mouse. Mouse embryos from day 13 to day 19 of gestation (E13 through E19) were removed by Caesarean section and their brains were prepared for electron microscopy. Coronal sections were examined in three planes through the ventromedial hypothalamus: anterior, the level at which the optic tracts pass posterolaterally to become partially enclosed in the major brain mass; middle, the level at which the floor of the third ventricle begins to widen and flatten; posterior, the level at which the most anterior infundibulum appears. Three types of junctional complexes were examined. Close junctions are identified as straight, parallel areas of two apposed membranes which appear more electron-dense than immediately adjacent regions. The membranes are separated by a clearly visible cleft. Unlike synapses, no clear synaptic vesicles are found in either of the adjacent profiles unless randomly distributed and accompanied by ribosomes or glycogen. Close junctions are seen most frequently on day E15, then decrease in number through E19. Their participation in synaptogenesis is discussed from temporal, morphological, distributional and quantitative perspectives and is provisionally rejected. Immature synapses show only the minimal membrane specialization found in close junctions, but vesicles are present, ribosomes absent in at least one of the adjacent cytoplasms. Their appearance peaks on E17-E18, paralleling and slightly preceding that of the mature synapses. Their evolution from close junctions has only weak temporal support. Mature synapses display the cytoplasmic densities which immature synapses lack. They attain their greatest prenatal numbers on E18, then decrease in number on E19. The conclusion is advanced that synaptogenesis does--or at least can--occur without the prior appearance of avesicular regions of increased membrane density.


Descending pathways from the brain stem to the spinal cord in some reptiles. I. Origin. In the present study of the origin of the pathways descending from the brain stem to the spinal cord has been investigated in the reptiles Testudo hermanni, Pseudemys scripta elegans, Tupinambis nigropunctatus and Python reticulatus. These reptiles, using highly different types of progression, have been selected, because fundamental variations in the organization of the central motor apparatus are to be expected. The origin of the descending pathways has been demonstrated by recording the occurrence of retrograde cell changes following hemicordotomies and by searching for labeled cells following injection into the spinal cord of the enzyme horseradish peroxidase. In the reptiles studies the presence of interstitiospinal, vestibulospinal and reticulospinal pathways could be demonstrated. A crossed rubrospinal tract has been shown in the turtles and in the lizard, but could not be demonstrated in the Python. The presence of a direct tectospinal pathway could not be shown.


Descending pathways from the brain stem to the spinal cord in some reptiles. II. Course and site of termination. The course and termination of the pathways descending from the brain stem to the spinal cord have been studied by tracing the ensuing anterograde fiber degeneration, following appropriate lesions in the reptiles Testudo hermanni, Tupinambis nigropunctatus and Python reticulatus. In these reptiles the presence of interstitiospinal, vestibulospinal and reticulospinal pathways has been demonstrated. A crossed rubrospinal tract has been shown in the turtle and lizard, but could not be demonstrated in the Python. The presence of a tectospinal pathway of any importance could not be shown. However, the tectum mesencephali has been found to project profusely to the brain stem reticular formation. The interstitiospinal tract projects predominantly to the ipsilateral side of the spinal cord. The vestibulospinal projection, arising from the large-celled nucleus vestibularis ventrolateralis, comprises a large uncrossed and a small decussating component. The rubrospinal pathway terminates in a particular area of the spinal gray, i.e., the intermediate zone, whereas the interstitiospainal, reticulospinal and vestibulospinal tracts all terminate in the medial part of the ventral horn. It appeared that the classification of descending pathways as advocated in mammals by Kuypers ('64) into lateral and medial systems can be readily applied to reptiles. The lateral system terminates in the dorsal and lateral parts of the intermediate zone, the medial system predominantely in the dorsomedial part of the ventral horn. This classification renders it likely that the absence of a lateral focus of termination as well as the absence of a rubrospinal tract in the Python, is correlated to the absence of limbs. A comparison of experimental data concerning the systems descending from the brain stem to the spinal cord in amphibians, reptiles, birds and mammals suggests that these systems with regard to origin, course and termination have a basic pattern in common.


Involvement of the avian hypothalamus in defensively conditioned heart rate change. Hypothalamic involvement in visually conditioned heart rate change (established by pairing light and foot-shock) was studied in 128 pigeons by evaluating conditioning performance following lesions of various hypothalamic areas. Extensive destruction of the posterior hypothalamus severely impaired development of conditioned heart rate change. Anterior hypothalamic lesions also produced serious deficits, though not as severe as following posterior hypothalamic damage. Partial posterior hypothalamic, unilateral and tuberal lesions produced only minor to moderate deficits. The critical locus for profound impairment of conditioned response development appeared to be the medial hypothalamus, and it is suggested that more specifically it is the terminal field of the archistriatal projection upon the medial hypothalamus. It is concluded that the medial hypothalamus is essential for the development of defensively conditioned heart rate change, and based on previous findings it is suggested that the critical descending pathway for expression of this conditioned response involves the archistriatal projection upon the medial hypothalamus and subsequently a polysynaptic pathway through the ventral brainstem.


Glial changes in the progress of a chemical lesion. An electron microscopic study. The response of non-neuronal cells in the brain to monosodium glutamate (MSG) was studied in the neonatal mouse brain. Neurons rapidly degenerate in this chemically-induced lesion, and the glia reflect and respond to their early pyknosis and death. Astrocytic glia exhibit the most profound responses in the form of degenerative nuclear and cytoplasmic changes within 15 to 20 minutes after ingestion of MSG. After 6 to 12 hours, a large glial cell population, containing neuronal and synaptic debris, can be seen. Recovery of severely damaged astrocytes is unlikely. Further, evidence of multiplication of uninjured cells to supply this observed repopulation was found. Microglia start to engulf debris at 6 to 12 hours and continue this process through at least 48 hours. From 3 to 48 hours, a third cell type, tentatively identified as a Gitter cell, is preminently involved in phagocytosis of neuronal elements. Nuclei of these cells enlarge and their parikarya become vastly expanded in a fashion typical of Gitter cells. These cells appear to represent the transformed microglia. Phagocytosis following a chemical lesion induced by glutamic acid, a neurotransmitter substance, is exceedingly rapid in comparison to that elicited by other types of lesions. Further, endogenous glial cells cope with the cellular debris; no participation in this process by hematogenous cells was observed.


Organization of the tectofugal visual pathway in the pigeon: a retrograde transport study. In birds, superficial laminae of the optic tectum receive a massive retinal input; the tectum in turn projects upon the nucleus rotundus thalami, which then sends its efferents to the ectostriatal core of the telencephalon. To examine the detailed organization of this principal ascending visual pathway, small injections of the marker horseradish peroxidase (HRP) were placed in various sites throughout the ectostriatum (E) or nucleus rotundus (Rt) in pigeons. Analysis of the resulting patterns of retrograde labeling indicates the tectofugal pathway to be comprised of at least five different channels. Cells which lie at various depths in the stratum griseum centrale (SGC) of the tectum project upon distinct subdivisions of nucleus rotundus. Anterior portions of Rt receive input from superficial-most cells in the SGC, while medial and more caudal portions of Rt are projected upon by deeper SGC neurons. A ventral subdivision of Rt was found to receive its primary input from two pretectal nuclei. Additional inputs to all portions of Rt arise from nucleus reticularis superior thalami. The various subdivisions of rotundus in turn project upon distinct portions of the ectostriatum. Thus, the segregation between the different input classes into Rt is largely retained at the telencephalic level. In contrast, the nucleus triangularis, a dorso-medial extension of Rt which receives its input from the deepest of all SGC neurons, sends its efferents to all parts of the ectostriatum.


Uses of double-pulse stimulation behaviorally to infer refractoriness, summation, convergence, and transmitter characteristics of hypothalamic reward systems. To self-administer trains of pulse pairs, rats with electrodes in the hypothalamic reward system would press a lever at lower current thresholds or faster latencies, the shorter the intrapair interval--unless the interval was so short that each second pulse fell within the refractory period following the first. By delivering all second pulses to the contralateral reward system not only was this refractory period limitation on temporal summation circumvented but spatial summation of the two reward systems was demonstrated. Evidently, they converge somewhere upon common neurons. Nearby nonreward structures did not share in this convergence. Assuming that the temporal-summation decline at longer intrapair intervals reflected the course of transmitter disposal at the synapse, imipramine and diisopropylfluorophosphate were peripherally administered. These drugs, which retard disposal, respectively, in adrenergic and cholinergic synapses, indeed prolonged temporal summation, thus, supporting the assumption and implying that adrenergic and cholinergic mechanisms both mediate self-stimulation.


Time-discrimination performance in cats with lesions in prefrontal cortex and caudate nucleus. Cats were trained on a time-discrimination task in which different periods of bodily confinement served as discriminanda for go-left/go-right responding. Lesions of gyrus proreus or the associated anteroventral part of nucleus caudatus impaired relearning in this situation. After reacquisition, animals with caudate lesions received proreal ablations and animals with cortical damage received caudate lesions; both additional lesions caused reappearance of the deficit. The absence of external stimuli to signal locus of reinforcement at the moment of spatial choice may have been crucial for eliciting the deficit. The data support the notion that the prefrontal cortex and the anatomically related part of the caudate nucleus participate in similar behaviors.


The dorsal tegmental noradrenergic projection: an analysis of its role in maze learning. The hypothesis that the noradrenergic projection from the locus coeruleus (LC) to the cerebral cortex and hippocampus is an important neural substrate for learning was evaluated. Maze performance was studied in rats receiving either electrolytic lesions of LC or 6-hydroxydopamine (6-OHDA) lesions of the dorsal tegmental noradrenergic projection. The LC lesions did not disrupt the acquisition of a running response for food reinforcement in an L-shaped runway, even though hippocampal-cortical norepinephrine (NE) was reduced to 29%. Greater telencephalic NE depletions (to 6% of control levels) produced by 6-OHDA also failed to disrupt the acquisition of this behavior or to impair the acquisition of a food-reinforced position habit in a T-maze. Neither locomotor activity nor habituation to a novel environment was affected by the 6-OHDA lesions. Rats with such lesions were, however, found to be significantly more distractible than were controls during the performance of a previously trained response. The hypothesis that telencephalic NE is of fundamental importance in learning was not supported. The data suggest that this system may participate in attentional mechanisms.


Roles of anoxia and noise-induced hearing loss in the postictal refractory period for audiogenic seizures in mice. The present series of experiments demonstrated a postictal refractory period for audiogenic seizures in DBA/2J mice, which was not related to hearing loss but apparently was related to anoxia. Unlike many previous studies, Experiment 1 controlled for the effects of noise exposure upon hearing sensitivity and demonstrated reduced susceptibility to subsequent audiogenic seizures for at least 1 hr after initial clonic-tonic convulsions. The postictal refractory period was shown to result from the occurrence of seizures per se, not from noise exposure alone. Experiment 2 demonstrated deficiencies of sensorimotor functions that accompanied reduced postictal seizure susceptibility. The two phenomena had similar time courses of recovery, which suggested a common mechanism, probably anoxia, associated with the initial convulsions. In support of this view, Experiment 3 showed that recovery from both phenomena was expedited by allowing subjects to breathe increased O2. The role of anoxia in fatal convulsions was suggested by the finding that subjects experiencing clonic-tonic convulsions in a high-O2 environment survived without exception. In contrast, seizures of air-breathing controls were almost always fatal. Taken together, the data indicate that the postictal reduced susceptibility to audiogenic seizures was closely related to metabolic depletion (in particular, anoxia). The pattern of recovery of susceptibility further suggests that the effects of anoxia impair the spread of seizure activity through the central nervous system, although the initiation of seizures is also affected for a short time.


Circadian rhythms and partial recovery of regulatory drinking in rats after lateral hypothalamic lesions. Rats that had recovered spontaneous ingestive behavior after lesions of the lateral hypothalamus were challenged with acute injections of hypertonic NaCl administered at different times during the day/night cycle. Following these injections, drinking was observed only during the nighttime. After morning injections the rats frequently waited until nightfall before drinking, whereas animals injected at night showed much shorter delays in the behavioral response; a similar nocturnal predominance of drinking was seen after food deprivation and in the ad-lib situation. Studies in blinded animals suggested that these effects were due to an endogenous circadian rhythm.


Sensitivity to low doses of ethanol and pentobarbital in mice selected for sensitivity to hypnotic doses of ethanol. These experiments assessed sensitivity to low doses of ethanol and pentobarbital in mice that had been selectively bred with respect to ethanol sleep time (the length of time an animal remains on its back following a hypnotic dose of ethanol). The hypothesis under investigation was that short-sleep (SS) mice might be more sensitive than long-sleep (LS) mice to excitatory effects produced by low doses of depressants. In support of this hypothesis SS mice were more active in an open-field test after ethanol than were LS mice. The lines did not differ in performance on a rotating-rod apparatus after these same doses of ethanol, suggesting that the difference in open-field activity was not attributable to a greater impairment of locomotor activity in LS mice. A similar difference in the open-field activity of the selected lines was observed with pentobarbital.


Relationship between composition and stability of bovine milk lysozyme. The amino acid analysis, peptide mapping, and heat stability of bovine milk lysozyme are presented. The bovine milk lysozyme molecule contains approximately 154 amino acids and is strikingly different in amino acid content from human milk lysozyme and egg white lysozyme. Tryptic hydrolysis yielded 26 peptides, all of which are unique from tryptic peptides of human milk lysozyme and egg white lysozyme. In addition, bovine milk lysozyme was more heat stable than human milk lysozyme at pH 4.0 but more labile at pH 7.0 and 9.0. Possible explanations for the differences in heat stability are discussed.


Limiting amino acid for protein synthesis with mammary cells in tissue culture. To identify the limiting amino acid in the minimal essential medium as published by Eagle (Science 130:432, 1959) for milk protein synthesis in rat mammary cells in tissue culture, two different experimental approaches were used. The first study involved the reduction of amino acids singly from the total amino acid complement of the medium for milk protein synthesis. The second study was to investigate the effect on milk protein synthesis of single amino acid addition to the basic complement of amino acids. Order of limiting amino acids was lysine (first) and possible methionine, valine, or arginine (second).


Effect of a synthetic corticoid on milk yield and composition and on blood metabolites and hormones in dairy cows. Twenty-five dairy cows were assigned randomly by breed to flumethasone treatment (10 mug/day, 13 cows) or placebo control (12 cows) from 4 to 44 wk of lactation. Lactation means and trends with stage of lactation were treatment responses. Mean milk yields of cows supplemented with flumethasone were not significantly different from controls. Mean metabolite (glucose, nonesterified fatty acids, and total esterified fatty acids) and hormone concentrations (corticoids, insulin, and prolactin) of blood plasma and their trends throughout lactation were unaffected by supplementation. Data were pooled to determine effects of stage of lactation, temperature, pregnancy, and month on these variables. Changes during lactation were systematic for feed intake, body weight, milk yield, milk components except somatic cells, blood metabolites, and prolactin. At environmental temperatures above 18 C, effects were consistently negative for milk yield and composition, but only above 26 C for feed intake. Prolactin of plasma increased with increasing temperature to 18.2 C and then decreased. No other plasma metabolite or hormone was affected by days pregnant, age, or temperature. Months affected feed intake, milk yield, milk fat percentages, all blood metabolites, and prolactin. Prolactin concentrations increased as daylight hours increased. Our inability to augment established lactation by feeding a supplement of synthetic glucocorticoid to lactating cows is consistent with the view that a lack of avialable corticoids does not limit persistency of lactation in the cow.


Failure to demonstrate transfer of milk prolactin into blood of milk-fed rats and calves. Possible absorption of ingested prolactin into blood of milk-fed neonates was studied in two species by different experimental approaches. In calves, secretion of endogenous prolactin was suppressed by administration of ergocryptine. Prolactin was measured in blood plasma  at 20-min intervals before and after ingestion by the calves of bovine milk or colostrum which contained prolactin. Prolactin in plasma during the 2-h period after feeding was the same as that during the 1-h period before feeding. therefore, these data failed to demonstrate any absorption of ingested prolactin into the blood of neonatal calves. Previous research showed that bovine prolactin could be transferred into rat milk by injecting it into lactating rats. Blood serum was collected from rat pups that were suckling dams previously injected with bovine prolactin. Several dosages and times of administration were used in the experimental design, and blood serum also was collected from rat pups nursing control dams. All samples were immunoassayed for bovine prolactin with reagents that crossreacted only slightly with endogenous rat prolactin. Injection of lactating dams with bovine prolactin did not increase the amount of immunoreactive bovine prolactin in the sera of suckling rat pups. These results agree with those from the calf study and indicate that ingested bovine prolactin was not absorbed intact into the blood of neonatal rats.


Rumen volatile fatty acids and milk composition from cows fed hay, haylage, or urea-treated corn silage. Alfalfa-brome hay, haylage, .5% urea-treated corn silage, or .5% urea plus 1% dried whey-treated corn silage was fed as the only forage to one of four groups of 10 lactating cows per group for a lactation trial of 10 wk. Rumen samples were collected via stomach tube 3 to 4 h after the morning feeding. The pH of the rumen samples from cows fed hay was higher than for cows fed haylage, urea-treated corn silage, and urea-whey corn silage, 6.69 versus 6.36, 6.40, and 6.50. Total volatile fatty acids and propionate were highest from cows fed urea-whey corn silage and were higher on all three fermented forages than cows fed hay. Acetate/propionate ratio was highest from cows fed hay and lowest from cows fed corn silages. Butyrate was highest from cows fed haylage or hay. Milk protein composition was not affected by ration although nonprotein nitrogen of milk was highest from cows fed the urea-treated corn silages. Oleic acid and total unsaturated fatty acids were lowest in milk fat from cows fed hay while palmitic acid was highest from cows fed hay and haylage. These results suggest that type of forage fed may cause small changes in rumen fermentation and in milk composition. The importance of these changes is unknown but may affect properties of dairy products produced from this milk.


Genetic parameters of several measures of milk flow rate and milking time. Heritabilities and genetic correlations of milking rate, time, and yield were estimated by intrasire regression of daughter on dam for 252 Holstein pairs. Heritabilities were: lactation yield, .51 +/- .11; peak rate, .47 +/- .11; bucket milk yield, .38 +/- .10; average rate, .37 +/- .12; milk yield to .45 kg/min, .19 +/- .12; total time, .17 +/- .12; duration of peak rate, .10 +/- .10; strip time, .08 +/- .15; yield during peak rate, .07 +/- .11; and strip yield, .01 +/- .17. The genetic correlation of peak rate with lactation milk yield was .69 +/- .08, indicating substantial genetic improvement in milking rate by selecting for milk production. The genetic correlation between total milking time and lactation milk yield was .50 +/- .20, indicating an increase in total milking time due to selection for milk. Direct selection for peak rate would provide an opportunity to reduce total milking time.


Social rank and physiological traits of dairy cows as influenced by changing group membership. Social behavior was observed in two groups of 17 cows during 13 wk to determine dominance rank. On the basis of dominance ranking during two bi-weekly intervals (wk 3 and 4, 7 and 8), a total of six cows was exchanged between groups (two during the first and four during the second exchange). The effect on milk yield, milk leucocyte concentration, and milk prolactin of dominance rank and introduction of "strange" cows into a group was studied. Dominance rank was greater for older, heavier, taller cows in a later stage of lactation. Fat-corrected-milk yield was greater for dominant cows but milk prolactin was lower. Dominace rank for cows moved to a new group did not change appreciably. Persistency of milk yield was associated negatively with dominance rank for five of six exchanged cows. Since the average persistency of milk yield for all cows dropped 5% from wk 7 to wk 8, it appears exchange of cows between groups affected both exchanged and nonexchanged cows in a random manner. Neither dominance rank nor exchanging cows between groups had a significant effect on leucocyte concentrations in milk. Milk-prolactin concentrations were most highly correlated with dominance rank, stage of lactation, body weight, and height at withers.


Detection of estrus in dairy cows by electrical measurements of vaginal mucus and by milk progesterone. Electrical resistance (ohms) of mucus were analyzed in 20 postpartum Holstein cows by use of a probe inserted into the anterior vagina every other day for 30 days. Composite milk samples were taken on the same day, and progesterone was determined by radioimmunoassay. Cows were observed twice daily for standing estrus and reproductive organs palpated weekly per rectum (rectal palpation). Fifteen cows which were cycling showed increasing progesterone 6 to 7 days after the onset of estrus with values of 8.1 to 10.0 ng progesterone/ml milk on days 10 to 17. Concentrations had declined rapidly 2 days before onset of the next estrus. Progesterone in milk was affected by cow and by day of the cycle. Electrical resistance followed a similar cyclical pattern, but variability was large and only cows differed. The correlation between milk progesterone and mucus resistance was .22. Progesterone concentrations for four cows with follicular cysts fluctuated randomly with a mean of 2.6 ng/ml. Mean resistance of vaginal mucus was 44 omega for both cycling and cystic cows, indicating that a single measurement of electrical resistance every 2nd day was unreliable in distinguishing physiological states. One cow had high progesterone in milk on days 19 to 25 and was diagnosed pregnant by rectal palpation 3 wk later. Cows were not seen in estrus 28% of the time when milk progesterone and rectal palpation indicated they were in the follicular phase of the estrous cycle and were cycling.


Ration digestibility and mineral balance in lactating cows fed rations containing dried whey. Including dried whey in rations of nonruminants usually increases digestibilities and mineral retention, presumably because of the lactose in the whey. A trial with total collection had five lactating cows per treatment to determine the effects of 5% dried whey product in the concentrate on digestibility of the ration and on absorption and retention of calcium, magnesium, and phosphorus. Rations included corn silage ad libitum, 3 kg alfalfa hay, and either control or dried whey product in concentrate ration at 1 kg/3 kg milk produced. Rations were balanced for content of nitrogen, calcium, magnesium, and phosphorus. Digestibilities of dry matter, nitrogen, and energy were not increased with dried whey product in the ration. Apparent absorption of calcium, magnesium, and phosphorus was not affected significantly by inclusion of whey in the ration. Productive (milk plus retained) calcium and magnesium were not increased when dried whey product was in the ration although productive phosphorus was slightly higher with the dried whey product. Adding small amounts of dried whey to a ruminant's ration will not increase mineral absorption and retention probably because tthe lactose in dried whey is fermented in the rumen and unavailabe for aiding absorption from the small intestine.


Sex-typed play in feminoid boys versus normal boys and girls. Procedures for assessing children's sex-typed play were developed which (a) examined children's continuous play in four sessions totaling 20 minutes rather than measuring only initial choice of a sex-typed toy, and (b) did not impose the stimulus-specific condition of requiring an adult experimenter to be present to administer the task. Play with "masculine" and "feminine" toys was observed for 120 normal children (60 boys, 60 girls) aged 3 yr.-8 yr., and 15 similarly aged boys diagnosed as having childhood gender disturbance. Significant differences were found in the sex-typed play of the two normal groups, but no age differences were observed. The amount of feminine play by the feminoid boys was found to be significantly greater than that of normal boys, but not significantly different from the predominantly feminine play patterns of the normal girls. The usefulness of such a measure for the clinical assessment of deviant sex-role development in young children is discussed.


Behavior problems in elementary school children a follow-up study. Two-year follow-up data for an ostensibly normal sample of children who had been previously characterized on a number of behavior problem dimensions by their teachers and peers were analyzed. In addition, 1-year follow-up data were presented for a group of extreme behavior children from the same school. The behavior dimensions of Distractibility and Conduct Problem were fairly stable over 2 years for girls and boys. In addition, Inadequacy-Immaturity was stable for girls and may mark more severe behavior problems for young girls. Behavior problems of young girls were more predictive of later achievement difficulties while behavior problems of boys were more predictive of peer and teacher difficulty. Finally, teacher's clinical judgement was demonstrated to be useful for indexing behavior for hyperactive boys.


The ecological assessment of an autistic child. The behavior of an autistic child was observed in his natural environment. Observations were made in three settings, over approximately 6 months. Sixteen behaviors of the child and six behaviors of adults and peers were recorded. A cluster analysis was performed to identify response classes within the behavioral structure of the child and to see if correlations existed between response  and stimulus events. To examine intra- and intersetting changes, Spearman rank correlations and t tests were also computed. The autistic child exhibited a diversity of behavior over time in a given setting and across settings. He persistently ignored other nonautistic children, although he was responsive to adults. Response classes reflected an inverse correlation between the child's self-stimulatory behaviors and his attentiveness to the environment. Elevated levels of adult attention were consistently related to reduced levels in most self-stimulatory behaviors. Two response classes showed inverse relationships between self-stimulatory behaviors. Reducing the frequency of some self-stimulatory behaviors might cause increases in others.


Attributional change and the importance of baseline recording a case illustration. This single case study illustrates how attention to baseline measures prevented premature conclusions regarding the impact of a conditioning procedure upon aggressive, acting-out behavior. Five disruptive behaviors were initially delineated so that frequency distributions could be obtained. During the course of this 15-day observational period, a significant reduction in the number of these aggressive responses was noted. The proposed conditioning procedure was therefore never required. Explanations as well as implications regarding the observed alteration in behavior were discussed.


Some detrimental effects of using extra stimuli to guide learning in normal and autistic children. This study was designed to assess the effectiveness of using prompts (extra "guiding" stimuli) for teaching normal and autistic children. One group of normal children was pretrained on a color discrimination. Later, the colors were used as prompts (presented simultaneously with new training stimuli) to teach four new discriminations. Another group of normal children was trained on the same discriminations with a trial-and-error procedure (i.e., no prompting). A third group consisted of autistic children who were trained on these discriminations using the prompt procedure. Analyses of the results showed the following. (1) The trial-and-error group of normal children acquired more discriminations than the prompt group of normal children. (2) A comparison of the two prompt groups showed that the autistics failed to transfer from the prompt cue to the training cue more often than the normal children; rather, the autistics generally continued responding to the faded color cue. (3) Autistic and normal children who failed to acquire the discriminations when trained with a prompt procedure did acquire these discriminations when no prompt was used. That is, the results suggest that the presentation of an extra guiding stimulus was detrimental to the acquisition of training discriminations for all subjects, and particularly so far autistic children. Therefore, the common practice of providing extra guiding stimuli in proportion to the severity of the learning disorder may actually be harmful to the learning of new skills. Implications of these results for future research are discussed.


Comparison of the WISC and WISC-R on a psychiatric adolescent impatient sample. The present study compared the WISC and WISC-R on a group of psychiatric adolescent inpatients. The results indicated high intercorrelationss between the two test versions but with the correlation linearly related to the changes in content and administration rules of the WISC-R. Analyses of variance indicated that, on the basis of the Full Scale IQ, the WISC is an "easier" test than the WISC-R.


Nutrition education for medical students. I. What is it? Where has it been? Why should it be taught? After an eight-year experience of introducing nutrition into the medical school curriculum of a new medical school, the author reflects on the state of the art. Questions are raised: What is nutrition? Is it part of medical education? If not, why not? Why should it be taught? The article ends with a note of optimism with reference to nutrition education in medical schools.


Nutrition education for medical students. II. Who shall teach it? Within what framework? How? There exists inadequate recognition, inadequate support, and inadequate attention to the subject of nutrion in medical schools. While progress has occurred in some schools, the teaching of nutrition has not generally been integrated into the curriculum of the medical school. This paper raises the question: Within what framework and how? The author attempts to highlight the role of the nutrition educator in the medical center setting as the health professional to assume leadership. There are signs of renewed interest. Efforts are being made to expand nutritional knowledge in the medical school curriculum. The design of nutrition in the curriculum must reflect the needs of society and of the learner. There must be relevance. The program must be problem-centered, affording the learners the opportunities to engage in the discovery of the role of nutrition in the health of people, the nutritional environment, and the interplay between the two.


Zinc content of selected foods.

Zinc content of selected foods. The zinc content of 174 foods was determined by atomic absorption spectrophotometry, using a dry ash preparation method. Data on some of the foods were not available elsewhere. Shellfish, cheese, meats, and nuts represented the highest sources of zinc found in this study. Soft drinks and other beverages, as well as vegetables generally, were poor sources of zinc.


Menu planning in the Nutrition Program for the Elderly. Modified Nutrient Standard Menu method. A nutrient standard menu (NSM) planning method was developed for use in planning menus which provided one-third the Recommended Dietary Allowances for persons sixty years of age or older for nine indicator nutrients and calories, while restricting fat to less than 40 per cent of total calories. To eliminate manual calculations and make it easy for individuals untrained in dietetics or nutrition to use NSM planning, the nutrient composition of over a thousand commonly used menu items was listed in a menu planning manual in nutrient units which were one-tenth of the nutrient standard for the meal. Menus from third-party sources were monitored by selecting similar nutritionally analyzed menu items in the manual and adjusting the nutrient composition to conform to the portions actually served. Ten site managers of the Administration on Aging (AoA) evaluated the planning/monitoring method. The members of the group, on the average, were fifty-six years of age, had 1.6 years of education beyond high school, and had 4.6 years of foodservice experience. Approximately 83 per cent of the evaluators did not plan to monitor menus at their sites and had no formal training in dietetics or nutrition. Eighty-four per cent were able to plan menus satisfactorily after this brief introduction. The younger evaluators with more education grasped the concepts faster and were able to plan menus with greater accuracy. The data also indicated that previous experience in menu planning enhanced their ability to plan NSMs. Most felt the approach to be workable and applicable. Menu monitoring was more difficult for the evaluators. Seventy-five per cent were able to monitor menus satisfactorily, and all felt they could do so with more time. The data again showed that the younger individuals having more formal education were able to master the monitoring skills more easily.


Dietary intake and coronary risk factors in Peruvian Quechua Indians. Some of the "risk" factors implicated in the etiology of coronary atherosclerotic heart disease were investigated in sixty Quechua men living in two areas of Peru. Highland Quechua had higher serum triglycerides (mean, 122 vs. 90 mg. per deciliter) than downward migrants. There were no significant differences between the two groups in serum cholesterol (mean 150 vs. 157 mg. per deciliter), body fat (mean, 15 vs. 17%), or blood pressure (mean, 113/72 vs. 114/72 mm Hg). Both groups consumed about 2,500 kcal per man per day, while the highland Quechua consumed more carbohydrate (mean, 66 vs. 51%) and less fat (mean 19 vs. 33%). By American standards, both groups had low serum cholesterol values, as well as low blood pressure.


Effects on pregnant adolescents of attending a special school. Data on nutrient intakes and blood vitamin levels were obtained for twenty-nine pregnant adolescents attending a special school for pregnant school-age girls in New Brunswick, New Jersey. Except for calcium and iron, mean intakes were equal to or greater than the Recommended Dietary Allowances. Food eaten at school contributed 35 to 43% of the total nutrient intake. Mean blood vitamin levels were normal to high, although about a fourth of the girls had low levels of vitamin B6 and folate. All except one delivered normal, full-term infants. It was concluded that attendance at such a special school contributes to normal pregnancy outcome among teen-age mothers.


Health food users in two Texas cities. Nutritional and socioeconomic implications. Health food buyers--both casual purchasers and confirmed customers of health food stores--were surveyed in Dallas and Houston. In both groups, users were generally in the middle class economically and in the active productive age brackets. Users in lower income groups spent larger proportions of their food budget in health food stores. The majority of confirmed users did so in the belief that such foods would provide health benefits, as health food proponents claim. Sixty-six per cent of the general public reported using vitamin and mineral supplements, compared with 93% of the confirmed health food users; the latter usually bought their supplements in health food stores, where megavitamins are likely to be promoted. Users among the general public, on the other hand, purchased supplements in drug stores and supermarkets as a rule.


Immunity and survival.

Immunity and survival. Studies in human families and in surviving older persons suggest that the immune system may have an important role in the control of the survival. Immune response (Ir) genes to infectious agents can be detected in human families.


Mortality fluctuations among chronically ill medical geriatric patients as an indicator of stress before and after relocation. The effects of mass transfer of a sick geriatric population of war veterans were evaluated to determine the resultant change in mortality. A comparison of mortality patterns by months during this interval made over a six-year period, centered around the month of the move, July 1971. Analysis of the mortality fluctuations in the 24-month interval surrounding the move indicated that the course of mortality during this interval was periodic, with four distinguishable phases making up the complete cycle. An attempt was made to link stress-inducing events before, during and after the relocation with the ensuing mortality. It is important to use planned, low-key, stress-prevention measures and continue them for some time after the move, to offset adverse mortality effects from anticipatory anxiety and from the postrelocation release of anxiety-generated stress.


Involuntary transfer as a cause of death and a medical hospitalization in geriatric neuropsychiatric patients. The effects of mass involuntary transfer on geriatric neuropsychiatric male patients were evaluated by comparing outcomes for three overlapping sets of patients (N = 403, 385, and 378) over several follow-up periods. One group, the "reorganization" sample, consisted of all patients on three geriatric wards at a time just before the wards were reorganized and 20 percent of the patients were transferred to other buildings. The comparison samples comprised two overlapping groups consisting of all patients on the wards four months earlier and four months later.


Large scale production, purification and a study of some spectral properties of Penitrem A. A large scale production of the tremorgenic toxin, Penitrem A, from the cultures of Penicillium (P.) palitans and P. crustosum for studying its spectral characteristics was attained. From several fermentation runs using Czapex-Dox medium, P. crustosum was shown to produce nearly 80% more toxic metabolite than P. palitans. A method involving silica-gel column chromatography for a single step isolation of the toxin from the crude extract of the mycelial mats was developed. Some spectral properties of Penitrem A were discussed.


A flame ionisation detector for the determination of nitrix oxide. Existing methods for the detection of nitric oxide are described, and their detection limits noted. The use of a flame ionisation detector is proposed, and the means by which its sensitivity toward nitrix oxide can be greatly enhanced is described. Detector operating conditions and response characteristics are given.


2,4-D levels in the South Saskatchewan River in 1973 as determined by GLC method. 2,4-D levels in the South Saskatchewan River near Saskatoon in 1973 at the height of the spraying season, and at harvestime, were determined by a method involving direct glc analysis, ankaline hydrolysis, followed by n-butylation of the liberated free acid after acidification of the alkaline solution, and confirmed by subsequent n-octylation. GC/MS also confirmed the presence of 2,4-D. 2,4-D was detected during the spraying season but not at harvest time or in river mud samples. The average level was ca. 2mug of acid equivalent to 2,4-D per liter of river water at the height of the spraying season.


Chemical transformation of S-benzyl O-ethyl phenylphosphonothiolate (Inezin) by ultraviolet light. The photodecomposition of Inezin (S-benzyl O-ethyl phenylphosphonothiolate) in n-hexane under the ultraviiolet irradiation was investigated by gas liquid chromatography, thin layer chromatography, mass spectrometry, and infrared spectroscopy. Two main steps of photodecomposition  were observed at the initial stage of irradiation. One was the cleavage of P-S bond to produce O-ethyl phenylphosphinate and dibenzyl disulfide, the latter of which was degraded rather rapidly to produce sulfuric acid and benzoic acid through toluene-alpha-sulfonic acid by oxidation. The other step was the isomerization to the thionate, O-benzyl O-ethyl phenylphosphonothionate, which was gradually oxidized to itx oxygen analogue, O-benzyl O-ethyl phenylphosphate. O-ethyl phenylphosphinate, O-benzyl O-ethyl phenylphosphonate and O-benzyl O-ethyl phenylphosphonthionate were fairly stable under the ultraviolet light, as compared with Inezin. As hydrolysis products of the parent compound, phenylphosphonic acid, O-ethyl hydrogen phenylphosphonate, O-ethyl hydrogen phenylphosphonothioate and benzyl alcohol were detected.


Influence of diet and feed restriction on kidney function of aging male rats. The influence of diet and feed restriction on kidney function was studied in aging male albino rats. Rats were fed either a commercial feed (LB) or a modified human diet (MHD) from weaning until sacrifice at either 12 or 24 mo. of age. Restricted rats were fed for only 15 out of each 48 hours. Feed restriction during either the first, the second, or both years of life was beneficial in delaying age-associated changes in kidney function as indicated by decreased proteinuria, increased in vitro transport of paraaminohippuric acid, and reduced incidence and severity of renal lesions. Urinary creatinine and blood urea nitrogen levels were also favorably influenced by restriction. Most parameters were modified by diet as well as by restriction, with MHD being generally associated with improved kidney function. Improvement in kidney function may have been more related to a reduction in protein intake than to a reduction in caloric intake as a whole.


Experimental allergic encephalomyelitis in aged F344 rats. Experimental allergic encephalomyelitis (EAE) was produced in 2- to 24-mo.-old F344 rats by active immunization and by passive transfer of lymphoid cells (adoptive immunization) from young rats. With both methods, some 24-mo.-old rats had a reduced ability to develop this autoimmune disease. However, the immunological deficit was related to incidental serious diseases rather than to old age per se. The aged F344 rat is not a suitable model for comparing EAE to multiple sclerosis in man because the decreased incidence of multiple sclerosis after the age of 50 is not related to other serious illnesses.


Depression in the elderly.

Depression in the elderly. Depressions in the elderly have many similarities to depressions in other age groups, particularly in their episodic nature, their tendency to remit, and their potential for favorable immediate outcome. They may, however, be far more easily overlooked. They often are considered to be consistent with senescence because of their frequent association with metabolic disturbance, with a variety of physical illnesses, with impaired cerebral function, and with hypochondriacal manifestations that may be viewed as characteristic of old age. It is important, therefore, that the clinician who treats these older patients be aware that depression is the psychiatric symptom he will most often encounter in the elderly and that it is as distressing in this age group as it is in younger persons. It represents an entity that often is reversible with prompt and appropriate treatment.


The comparative frequency of depression in various adult age groups. This paper reviews some methodological problems in assessing the age distribution of depression, catalogues and summarizes the findings of various epidemiological surveys, and discusses the implications of these findings from the view point of public health, clinical diagnosis, and research into the etiology of depression.


Age differentiation in depression: biochemical aspects. No age is immune to depression but the elderly seem especially susceptible since the incidence and prevalence is highest in the age group 55-70. At all ages the causes of depression are multiple and not fully understood. Elderly people who have been prone to depression earlier in life are especially vulnerable to major life stresses but the incidence rises even among those who have not had depressions earlier in life. Evidence based largely upon the mechanism of action of drugs specifically therapeutic for depression suggests that depression is associated with alterations in the synthesis, storage, release, and utilization of chemical neurotransmitters. Enzymes involved in these mechanisms are under genetic control. Furthermore, alterations in the activity of these enzymes occur with aging. The interaction of these biological and psychosocial changes relates to increased depression in the elderly. Treatment with tricyclic antidepressants is usually effective but must be reinforced with appropriate environmental support systems.


The age factor in depressive illness: some genetic considerations. The age of onset of depressive illness may have an association with the genetic character and clinical course of the disorder. There are several genetic models of depressive disorder that are based on differences in age of onset. According to a multifactorial model, for example, a late onset would indicate a smaller genetic and greater environmental component. A correlation has been found between positive family history of affective illness and early age of the first episode. The presence or absence of a family history of affective illness has also been found to be distinguished by pharmacology, physiology, symptomatology, and severity. It is therefore recommended, for purposes of treatment, that a family history be gathered on patients with depressive illness.


Somatic therapies in older depressed patients. While psychotherapy is the treatment of choice in neurotic situational depressions of older patients, it is not effective enough in endogenous bipolar or monopolar depression of elderly. These respond better to somatic therapy, mainly pharmacotherapy, or, if necessary, ECT. Experience shows the aged endogenous depressions respond favorably to tricyclic antidepressants as well as to mono-amino oxidase inhibitors, although the dosage may have to be kept lower than with younger patients. ECT, if necessary, is well tolerated and effective in aged patients. However, proper precautions have to be taken before this treatment is commenced. Patients with a history or signs of recent coronary thrombosis or decompensated heart failure should be excluded. Also, the number of treatments should be kept at a minimum. The individual treatments should be spaced farther apart and so-called "intensive treatment" avoided. If an endogenous depression lasts for more than 2 years and does not respond to any other kind of treatment, psychosurgery may have to be considered. Experience has shown that long-lasting, deep depressions of the aged can be helped by this method without any important personality change.


The therapeutic milieu and the older depressed patient. A team screening referrals for admission to a state hospital evaluated 434 consecutive cases. Over 51% had a diagnosis of depression. By treating patients in the community, including brief local hospitalization where indicated, total geriatric admission were reduced by 50% per annum. In the final phase of the program, only 10% of admissions to the state hospital were for a primary diagnosis of depression. Almost half of the evaluations required only examination and recommendations, treatment being undertaken by the referring source or another community agency. A further 22% required but one visit to initiate therapy. 17.6% were admitted to treatment, which included drug and group therapy and also milieu therapy by means of transfer, environmental manipulation, and attitude therapy. Only 11.3% needed to be seen weekly or oftener. The program results in considerable savings by reducing unnecessary hospitalization.


Age and clinical depression: today's youth in the twenty-first century. Clinical depression is on the increase in adolescence and young adulthood. Since World War II, psychiatrists are seeing depressed patients who are younger, less severly ill, and more commonly neurotic than psychotic. These patients are most often seen in outpatient and ambulatory settings rather than inpatient hospital facilities. Several reasons have been postulated for this increase; (1) the baby boom following World War II increased the number of people in this age group and (2) the sheer number of people created stresses with which conventional social institutions cannot cope. A shrinking economy and other forces blocking economic gain counteract rising expectations of all young adults, and a situation is created that gives rise to loss of self-esteem, frustation, and perhaps a rising incidence of depression. However, this is just one factor of many which interact which might cause depression. A serious question is whether the reactive depressions of youth will pave the way for endogenous depression in adulthood and old age. Research is needed to determine whether youth will be predisposed to further depressive episodes and, if so, will we be entering a new age of melancholy?


Aging and depression: some unanswered questions. The subject of aging and depression leaves many unanswered questions, and the lack of precise and universally accepted definitions (not to mention an inadequate nosology) further complicates the issue. Little is known regarding the differentiation of depressive illness from a melancholic response to the stressful aging process, and equally little regarding the natural history of depressions with onset in the teens, 20s, or 30s. Studies are focusing on biochemical and physiological aspects of depression, but at present biochemists suffer from the uncertainties of the clinicians, and the clinicians and geneticists from the limitations of the biochemists. However, despite our uncertainties about the condition, several effective forms of therapy have been developed, ranging from a focus on the therapeutic milieu to the use of pharmacologic antidepressants (particularly lithium). Ultimately, the question remains: Why are not all elderly persons suffering from depression? The answer may lie in the interaction of environment, life stresses, and the internal adaptive capacities of the individual.


Cognitive strategy training and intellectual performance in the elderly. Reduced intellectual performance in the elderly was conceptualized as an experientail deficit than can be reversed by training relevant component skills. Sixty female elderly subjects (ages 63 to 95) participated in three phases of the experiment: Training, Immediate Posttest, and Delayed Posttest. Training was geared at strengthening covert self-monitoring strategies in complex reasoning problems, and training effects were evaluated both on the training and a transfer task. Results showed raised performance in the training conditions, transfer effects, and maintenance of training and transfer effects over 2 weeks. Implications for theories of adult intelligence are discussed.