A biological oscillator system and the development of sleep-waking behavior during early infancy. The sleep-waking behavior of a male infant, normal with respect to pregnancy, delivery and Apgar score, was observed continuously from birth till the first 4 months of life. The infant was allowed to sleep and awake according to his own schedule and was fed only if his behavior could be judged as a feeding demand. Using several methods of computerized analysis it could be demonstrated that the spontaneous sleep-waking behavior was mainly driven by two endogenous rhythms, an ultradian cycle and a circadian one. While the ultradian rhythm was already established at term showing a mean period of 4 h, the circadian variation developed during the first 3 months of life. So far our results support earlier studies (KLEITMAN and ENGELMANN; PARMELEE; HELLBRUGGE,). The present paper, however, gives further evidence that both rhythms do not run independently, but seem to constitute a system of connected oscillators. As soon as the circadian rhythm is manifestly developed, the period of the ultradian rhythm seems to be modulated according to circadian variations. More specifically, during the nocturnal phase of the circadian rhythm the ultradian rhythm decelerated. By contrast, during the diurnal phase the ultradian cycle was accelerated. Using circadian frequency modulation of the ultradian cycle as the underlying principle, a computerized model of both connected oscillators was developed. The theoretically predicted sleep-waking behavior was compared to the behavior actually observed in the infant of this study. During postnatal development the coupled rhythms cause characteristic periodicities of the sleep-waking pattern. Since the infant experiences his world within a basic framework of sleep and waking spans, the different periodicities may be considered as a structure timing the information process in the developing brain.


Effects of adrenalectomy on body weight and the size and number of fat cells in the Zucker (fatty) rat. Adrenalectomy reduced food intake and the rate of weight gain in the Zucker (fatty) rat to levels indistinguishable from normal. The size of adipocytes in the retroperitoneal and perimetrial fat pads also decreased after adrenalectomy but the number of fat cells in each of these depots increased to reach levels not different from those in the sham-operated fatty rat. Fat accretion in the intact fatty rat was characterized by both hyperplasia and hypertrophy of the fat cells, but in the adrenalectomized Zucker rats, weight gain was accompanied by hyperplasia and decreased fat cell size. These data show that adrenalectomy can prevent most of the phenotypic expression of the genetic defect in the fatty rat and challenge the concept that reduced food intake can prevent hyperplasia of fat cells.


The effects of pinealectomy on pituitary prolactin levels in Carassius auratus exposed to various photoperiod-temperature regimes. Pinealectomy has an influence on pituitary prolactin levels in goldfish maintained under certain photoperiod-temperature regimes. The effects of pinealectomy on pituitary prolactin content depend on photoperiod and time of sampling. Thus, differences between pinealectomized and sham operated animals may be due to a shift of a daily variation in pituitary prolactin levels. The pineal in fishes may thus be involved in photoperiod influences on daily prolactin rhythms.


Comparison of steroid receptors from the androgen responsive DDT1 cell line and the nonresponsive HVP cell line. Two hamster cell lines have been isolated from androgen target tissue. The DDT1 cells derived from ductus deferens tissue exhibit a growth response to androgens, while the HVP cells derived from ventral prostate are androgen unresponsive. Both cell lines contain androgen receptors, that are similar when compared by kinetic methods, sedimentation velocity, chromatographic procedures or nuclear translocation ability. The forms of the high salt extracted nuclear receptors are indistinguishable chromatographically. Therefore, we postulate that the lesion preventing androgen induced growth in the HVP cell line is subseqent to nuclear translocation of the steroid receptor complex.


Differential effects of elevated potassium ion concentration and of theophylline on growth hormone release by rat adenohypophyses in vitro. The effects of 27 mM K+ and of 6.7 mM theophylline on the release of growth hormone (GH) by rat hemipituitaries in vitro were investigated using bioassay (rat tibia test) and radioimmunoassay (RIA). Both agents markedly increased the release of immunoreactive GH. High K+ also promoted the release of bioactive GH but to a much lesser degree than RIA-GH. Theophylline did not consistently affect the release of bioassay-detectable GH. The results suggest that these agents promote massive release of a form of immunoreactive GH (possibly "immature") that has little or no activity in the bioassay. Theophylline is relatively more effective in this regard than is elevated K+.


Interactions of bovine thyrotropin and human chorionic gonadotropin with adenylate cyclase in bovine thyroid membranes. Previous studies have shown that crude preparations of human chorionic gonadotropin bind to bovine thyroid membranes, displace 125I-labeled bovine thyrotropin therefrom, and are weak agonists therein with respect to the activation of adenylate cyclase. The present studies reveal that concentrations of chorionic gonadotropin sufficient to elicit a maximal agonistic response of adenylate cyclase are strongly antagonistic to the stimulatory action of bovine thyrotropin in the thyroid membrane system. This effect is reminiscent of the inhibitory effects of crude human chorionic gonadotropin on other extragonadal tissues in vitro, and, like them, appears to be mediated by some factor(s) other than human chorionic gonadotropin itself, since highly purified human chorionic gonadotropin was without effect.


Early effects of parathyroid hormone on rat calvarian bone alkaline phosphatase. Using a quantitative cytochemical method, explanted calvaria of 1- to 6-day-old male rats were used for the measurement of the in situ effect of parathyroid hormone (PTH) on the activity of alkaline phosphatase (AP) in the calcifying bone. The earliest effect of PTH was observed at 4--7 min. The direction and magnitude of the response of AP was dependent on the age of the animal and on the dose of PTH (50 fg-500 pg/ml). The calvaria of younger animals (2-days old) showed a decrease in AP activity, whereas in 5-day-old rats, AP activity was stimulated by PTH. In 5-day-old animals, the linear dependence of ATP stimulation on the PTH dose in the concentration range 50 fg-50 pg/ml could serve as the basis for a bioassay of a high sensitivity. The age-dependent response of AP to PTH may reflect the difference between the early and late stages of the calcification process. Our observations may reconcile conflicting reports on the effect of PTH on bone AP.


Glucose and insulin in the regulation of glucagon release from the isolated perfused dog stomach. The respective roles of glucose and insulin in the regulation of glucagon release from the canine stomach were investigated using an isolated blood-perfused preparation. At normal blood glucose and plasma insulin levels, the stomach released small amounts of glucagon. Such basal gastric glucagon release was not modified by hyperglycemia. In contrast, gastric glucagon release was increased by hypoglycemia or 2-deoxy-D-glucose-induced cytoglycopenia. Antibody neutralization of basal circulating concentrations of insulin (10 +/- 1 microU/ml) doubled the stimulation induced by hypoglycemia alone. It is concluded that: 1) suppression of gastric glucagon release is observed with very low concentrations of insulin; 2) basal gastric glucagon release is not further suppressed by hyperglycemia; and 3) that hypoglycemia and cytoglycopenia stimulate gastric glucagon secretion.


Selective blockade of estrogen-induced uterine responses by the antiestrogen nafoxidine. The response of the immature rat uterus to the antiestrogen, nafoxidine (Upjohn U-11, 100A), is maximum at a dose of 5 micrograms. This dose of nafoxidine sustains the uterine response for at least 72 h. After treatment with 5 micrograms nafoxidine for 24 h, uterine cytosol contains approximately one half the total number of estrogen receptors originally present in uteri of untreated animals, and uterine nuclei also contain approximately one half the receptors originally present in unstimulated tissue. The total amount of uterine estrogen receptor, however, is not altered 24 h after treatment with nafoxidine relative to saline-treated controls, while estradiol treatment doubles the total amount of receptor relative to controls. Pretreatment with 5 micrograms nafoxidine for 24 h does not block the uterine response occurring 4 h after the subsequent administration of estradiol, but does block the uterine response occurring 24 h after the subsequent administration of estradiol. These results suggest that uterine nuclei contain different acceptor sites for regulating short term and long term uterine responses to estrogen.


Comparison of luteolytic potencies of aminoglutethimide enantiomers in the rabbit and rat. The luteolytic potency of D- and L-aminoglutethimide (D- and L-AG) was compared in in vivo assays in the rat and rabbit. By assay of plasma progesterone depletion in the rabbit, the potency of L-AG relative to D-AG was 0.21. By the plasma procedure in the rat, the relative potencies of L-AG and of the racemic mixture to D-AG were 0.04 and 0.37, respectively. By the ovarian progesterone depletion method, the L-form had very little activity and the DL-mixture was half as active as the D-isomer. Thus, in both species, almost all of the activity of the racemic mixture results from the content of D-AG. Interpretation of paradoxical data implies that in the rat, L-AG may inhibit liver degradation of progesterone at levels which do not modify secretion from the corpus luteum.


Estrogen receptor in adult male rat liver. A 30% ammonium sulfate precipitation has previously been utilized to partially purify the estrogen receptor(s) of female rat liver cytosol. This procedure has now been used to fractionate the estradiol-binding sites of adult male rat liver cytosol. The 30% ammonium sulfate precipitation partially purifies a group of estradiol-binding sites which have properties quite distinct from the large number of sites present in male liver cytosol. The partially purified male sites seem to have the same properties as the partially purified female estradiol-binding sites. They seem to be proteins that are estrogen specific and have a high estradiol affinity (Kd = 1 X 10(-10) M) and a low estrogen capacity (2.3 fmol/mg liver). The estradiol-binding sites of prepubescent male rat liver cytosol have also been fractionated by 30% ammonium sulfate precipitation. The redissolved ammonium sulfate precipitates from prepubescent male rat liver cytosol contain fewer estradiol-binding sites then those from adult male or female rats. It seems that adult male as well as adult female rat liver contains estrogen receptors.


Cytoplasmic 17 beta-[3H]estradiol binding in rat adipose tissues. Ovarian hormones, particularly 17 beta-estradiol, have important effects on body fat levels in rats, but it is not known whether 17 beta-estradiol can act directly on various fat depots to affect adiposity or whether these effects are entirely indirect (e.g. via food intake, exercise, or various metabolic actions). We have found high affinity, estrogen-specific macromolecular binding of 17 beta-[3H]estradiol in the cytoplasmic fraction of adipose tissues from ovariectomized rats. Saturation analysis indicates a Kd of 7.4 X 10(-10) M, and binding is inhibited by unlabeled 17 beta-estradiol or 11 beta-methoxy-17-ethynyl-1,3,5(10)-triene-3,17beta-diol (R2858) but not by progesterone, 5 alpha-dihydrotestosterone, or cortisol. 17 beta-[3H]Estradiol binding is virtually abolished by incubation with pronase but not with DNase or RNase, indicating that the binding macromolecule is probably a protein. Binding is seen in all adipose tissues studied, including abdominal, sc, and brown fat. Binding site concentration is highest in parametrial fat pads, followed by retroperitoneal, brown, omental, and inguinal depots. Binding is also seen in the cytoplasmic fraction of isolated parametrial adipocytes. These data indicate that the various adipose tissues might be estrogen target tissues in rats. Therefore, it is possible that estrogenic effects on body weight and composition could be mediated in part by direct estrogen action on adipose tissues.


Hormonal control of nuclear estradiol receptor content and the luminal epithelium in the uterus of the golden hamster. Uteri were removed and blood was drawn from hamsters during the estrous cycle, on the eighth day of pregnancy, and after different hormonal treatments. Serum estradiol (E2) and progesterone (P) levels were determined by RIA. Portions of the uteri were prepared for light and electron microscopy. Endogenous uterine nuclear E2 receptor was measured by exchange assay. Large increments of nuclear E2 receptor occurred when the level of serum E2 was rising and that of serum P was falling (diestrus day 2 through proestrus morning); decrements occurred when the serum E2 level was falling and the serum P level was rising (proestrus evening through diestrus day 1). Ovariectomy on proestrus morning led to a decline in the amount of nuclear E2 receptor, and this decline was prevented by administration of E2 at the time of ovariectomy. P depleted nuclear E2 receptor in the presence of high levels of serum E2. The uterine luminal epithelium passed through a phase of mitosis and hypertrophy (diestrus day 2 through proestrus morning), a brief phase suggestive of secretion (proestrus evening), a phase of degeneration (estrus), and a phase of quiescence (diestrus day I). Ovariectomy on proestrus morning led within 24 h to degenerative changes identical to those seen during estrus, and these changes were prevented by treatment with E2 at the time of ovariectomy. P induced these degenerative changes in the presence of high levels of serum E2. After 8 days of pregnancy, the epithelium resembled that seen during diestrus day 1. Elevated uterine nuclear E2 receptor levels were associated with growth and hypertrophy of the luminal epithelium, and severely depressed levels were associated with the degenerative and quiescent phases of the epithelium.


Estrogen control of progesterone receptor in human breast cancer: role of estradiol and antiestrogen. Estrogen antagonists are widely used in the treatment of breast cancer, and studies of their mechanism of action may provide clues to an understanding of tumor growth regulation and mechanisms of normal estrogen action. We have used human breast cancer cells in long term culture as an in vitro model to study the roles of estradiol and the antiestrogens, tamoxifen and nafoxidine, on cell growth and progesterone receptor (PgR) induction. Tamoxifen is found to have dual dose-dependent estrogenic/antiestrogenic properties. With 1 micrometer tamoxifen, cell growth and PgR induction are suppressed. These effects are reversed by estradiol. At lower doses (less than 0.1 micrometer), however, tamoxifen is a potent estrogen and rapidly induces (24--48 h) PgR, which increases 4- to 10-fold after 4--6 days and falls if tamoxifen is removed. Induction of PgR by estradiol is weaker but follows a similar time course. Tamoxifen-induced PgR is similar to that induced by estradiol; it sediments at 8S on sucrose density gradients, is a tight binder (R5020 Kd, 1.7 micrometer at 4 C and 0.87 nM at 15 C), and can be translocated to the nucleus by R5020. The dual properties of tamoxifen are not due to metabolic formation of an active antiestrogen from a prohormone precursor. In contrast, the action of the antiestrogen nafoxidine is not biphasic in MCF-7 cells; it does not induce PgR over a wide dose range and at high doses, the compound inhibits cell growth.


Stimulation of ovine placental lactogen secretion by arginine infusion. Arginine has been demonstrated to be a potent stimulus to GH and PRL secretion. To determine the effect of arginine on plasma ovine placental lactogen (oPL) concentrations, arginine (50 g in 350 ml distilled water, pH 7.4) or hypertonic saline of identical volume, osmolality, and pH was infused iv over a 30-min period into nine pregnant ewes, and blood samples from chronic indwelling venous catheters were obtained at frequent intervals before and for 8 h after the infusions. After the infusion of hypertonic saline, plasma oPL concentrations (measured by homologous RIA) decreased 20--50% over 1--2 h and then returned to baseline concentrations. After the infusion of arginine, plasma oPL concentrations also decreased by 20--50% for 1--2 h. However, 2--3 h after the infusion, plasma oPL concentrations in creased 79--115% (delta = 204--700 ng/ml) over preinfusion concentrations in seven ewes and 454% (2930 ng/ml) and 1142% (2042 ng/ml) in two ewes and remained elevated for the remainder of the 8-h interval. When the amount of arginine infused was reduced from 50 to 25 g, an increase in plasma oPL concentrations occurred in only one of five ewes. Plasma oPL concentrations increased by 8--58% after infusions of 50 g alanine or glycine but did not increase after 50 g glutamic acid. The delayed oPL response to arginine suggests that the increase in plasma oPL concentrations is not caused directly by arginine but rather by changes in the synthesis, secretion, and/or degradation of oPL induced indirectly by arginine.


Identification of a tripeptidyl aminopeptidase in the anterior pituitary gland: effect on the chemical and biological properties of rat and bovine growth hormones. The NH2-terminal heterogeneity which is generated in bovine GH during its extraction from mildly acidified pituitary homogenates is attributable to a newly identified peptidase. The beta-naphthylamide of Phe-Pro-Ala, modeled after the NH2-terminal tripeptide sequence of the phenylalanyl monomer of bovine growth hormone, was cleaved by the peptidase into the tripeptide and B-naphthylamine and served as a substrate for assay of the eznyme. However, the B-naphthylamide of Ala-Phe-Pro, modeled after the NH2-terminal tripeptide sequence of the alanyl monomer, was not cleaved. In harmony with this specificity, the peptidase cleaved 11 tripeptides sequentially from the NH2-terminus of the phenylalanyl monomer of bovine GH but none from the alanyl monomer. Six of the tripeptides nearest the NH2-terminus were unequivocally identified and their sequences were consistent with the NH2-terminal octadecapeptide sequence of the phenylalanyl monomer of bovine GH. Five additional peptides were by composition consistent with their being tripeptides derived from residues 19--33. Because of the apparent specificity for the hydrolytic release of tripeptides and inability to cleave substituted tripeptidyl derivatives, the enzyme is considered to be a tripeptidyl aminopeptidase. In its hydrolysis of phenylalanyl monomers of rat growth hormone, a similar number of tripeptides was released, associated with which there was a 70% loss of biological activity but no reduction in immunological activity. The enzyme could be solubilized by extraction with 1% Triton X-100 at pH 3.0, precipitated between 2 and 3 M (NH4)2SO4, and further purified by gel filtration on G-75 in M/10 acetic acid. The enzyme has a mol wt of 57,000 and is optimally active at pH 4. It can be differentiated from cathepsin D by its insensitivity to inhibition by pepstatin.


Hormonal control of male reproductive behavior in the lizard, Anolis carolinensis: role of testosterone, dihydrotestosterone, and estradiol. The androgen aromatization hypothesis was examined in the male lizard, Anolis carolinensis. After castration, sc silastic implants of testosterone (T) restored both challenge and courtship behavior, while dihydrotestosterone (DHT) or 17beta-estradiol (E) had no effect on male behaviors. Both T and DHT, but not E, stimulated hypertrophy and colloid production by the renal sex segment, a secondary sexual characteristic of male lizards. In two separate studies, castrates received DHT in combination with E. In each replicate, half of the castrates responded with increases in courtship behavior after hormone treatment. Epithelial cell height of the sex segment of all DHT and E-treated castrates was comparable to T- or DHT-treated castrates, but colloid production was not stimulated. These experiments indicate that in this species, treatment with T stimulates both sexual behavior and secondary sex character development, whereas treatment with E alone is without effect centrally or peripherally.


Hormonal secretion by hyperactive thyroid cells is not secondary to apical phagocytosis. Hyperactive dog thyroids were prepared by repeated TSH stimulation in vivo. Butanol-extractable 125I (BE125I) release in vitro from slices and hormonal secretion in vivo in the thyroid vein was enhanced. Apical pseudopods and colloid droplets were very infrequent in such hyperactive thyroids. Moreover, BE125I release was insensitive to cytochalasin B, to inhibitors of microtubules, and to metabolic inhibitors, and decreased only with temperature. Our data demonstrate that hormonal secretion by hyperactive thyroids is not secondary to apical phagocytosis (i.e. macropinocytosis). Micropinocytosis or intraluminal hydrolysis of thyroglobulin are suggested as first step of the secretory process.


Effect of handling and forced immobilization on rat plasma levels of epinephrine, norepinephrine, and dopamine-beta-hydroxylase. Forced immobilization of rats triggers activation of adrenal-medullary discharge of epinephrine (EPI) and sympathetic neuronal release of norepinephrine (NE). Plasma levels of EPI reach peak values, which are about 40-fold greater than in undisturbed rats, at about 20 min and then decline to about one-third the peak levels. Plasma levels of NE are increased about 6-fold throughout the immobilization interval. Decapitation produces an 80-fold increase in plasma levels of EPI and an 8-fold increase in NE. These striking decapitation-induced increases are potentiated about 3-fold by immobilization, presumably as a consequence of an immobilization-induced alteration in the "set" of responsivity of spinal cord mechanisms controlling sympathoadrenal medullary discharge. Even minor disturbances produce highly significant increases in plasma EPI and NE and special precautions must be observed when studies involving plasma catecholamines or their effects are performed in animals.


Suppression of serum follicle-stimulating hormone by follicular fluid in the maximally estrogenized, ovariectomized mouse. Serum levels of FSH in ovariectomized female mice are only partially suppressed by estradiol regardless of the dosage administered. Conversely, within the limits of detection, serum FSH in intact females is totally suppressed by estradiol. Thus, the present experiments used the maximally estrogenized, ovariectomized female as a test system for evaluating other nonestrogenic factors which could depress serum FSH. It was found that a transplanted ovary lowered serum FSH dramatically under such conditions. Of the large number of steroid and pituitary hormones tested, however, only large doses of testosterone propionate yielded any further suppression of serum FSH (24%). Charcoal-extracted follicular fluid (porcine) markedly lowered serum FSH concentrations (50% suppression), while a charcoal-extracted saline homogenate of PMS-treated mouse ovaries also was active in this regard (26% suppression). Finally, charcoal-extracted porcine follicular fluid was administered to nonestrogenized, ovariectomized females, where it both depressed serum FSH and markedly elevated serum LH concentrations. These studies, when viewed in toto, support a contention that follicular fluid contains a nonsteroidal factor which is capable of acting additively with estradiol to regulate FSH secretion. The question of whether this factor also regulates LH secretion in a reciprocal fashion in the mouse requires further work.


Stoichiometric translocation of the rat uterine progesterone receptor. In several previous studies nuclear accumulation of the progesterone receptor was significantly lower than the quantity depleted from the cytosol one h after progesterone injection. The results presented herein indicate that this apparent lack of stoichiometry is due to loss of detectable receptor from the nucleus during the nuclear washes and after the assay incubation. This decrease in measured receptor results both from solubilization of the receptor-progesterone complex into the supernatant and from dissociation of [3H] ligand from the receptor. Conversely, no significant quantities of receptor were detected in the mitochondrial/microsomal fraction, preincubation nuclear washes, second ethanol extraction of the nuclear pellet, and soluene digest of the extracted pellet. Thin layer chromatography of the radioactive ligand bound to the nuclear receptor after in vitro exchange confirmed that virtually all the specific binding was due to [3H] progesterone, in spite of a 30% conversion to other metabolites in the incubation fluid.


Antisomatostatin serum increases levels of hormones from the pituitary and gut, but not from the pancreas. The effects of antisomatostatin serum upon the levels of growth hormone, glucagon-like immunoreactivity (GLI), glucagon, insulin and post-prandial triglyceride levels were examined in a group of 5 dogs before and after a fat-rich meal. Within 1 min after the injection of sheep antisomatostatin, plasma growth hormone and GLI levels increased significantly above baseline levels before the meal and remained elevated for 45 to 60 min after the meal, whereas the administration of nonimmune sheep serum to the same dogs did not cause significant changes in either hormone. Plasma insulin, glucagon and triglyceride levels after antisomatostatin serum were not significantly different from the controls. These findings suggest that endogenous somatostatin influences the secretion of growth hormone and GLI via a pathway readily accessible to intravenously injected antibodies, probably via the circulation, whereas any influence that somatostatin may have upon the secretion of insulin and glucagon must take place via a pathway inaccessible to intravenously administered antisomatostatin serum, i.e. within the islets themselves.


Characterization of an antiserum used in a radioimmunoassay for arginine-vasopressin: implications for reference standards. The region of the arginine-vasopressin (AVP) molecule critical for binding to the effective antibodies in a RIA has been localized to the vicinity of the Phe3 position by using the cross-reaction in the assay between AVP and a number of its structural analogs. Binding seems to be almost independent of any direct contributions from components of the tripeptide tail of AVP. Using this RIA it was found that disequilibrium conditions of incubation produce a 5-fold increase in assay sensitivity over equilibrium conditions. Amino acid analysis revealed that three synthetic peptide preparations used as reference standards comprised only 70-80% of their weight as peptide and this finding points up the need to correct such reference standards for their peptide content. The ratio of rat vasopressor activity to RIA activity of these three preparations as well as of a natural AVP preparation, however, approximated unity. Results obtained comparing measurements of AVP in rat neural lobes by RIA and rat vasopressor assay show a correlation between RIA and bioassay of 0.9406, a slope of 1.086, and an intercept of 20 mU, suggesting good agreement for AVP determined by these two assay systems.


Changes in testicular weight and serum gonadotropin and testosterone levels before, during, and after birth in the perinatal rat. Changes in serum and pituitary LH and FSH concentrations have been measured in the newborn male rat before, during, and up to 24 h after birth. A sudden and transient increase of serum and pituitary gonadotropins is observed at birth, which is followed by a rapid increase of absolute and relative testicular weights between 2--12 h (P less than 0.0001) and by a transient increase of serum testosterone between 0 h in utero (810 +/- 26 pg/ml) and 2 h (2820 +/- 318 pg/ml; P less than 0.0001). Similarly, premature newborn rats obtained by cesarian delivery on day 20 of gestation also exhibited an increase in testicular weight between 0--6 h and an increase in serum testosterone levels between 0 h (730 +/- 170 pg/ml) and 2 h (3400 +/- 300 pg/ml; P less than 0.001) with only a slight increase in serum LH. These results show that the hypophyseo-testicular axis of the rats is stimulated at the moment of birth. The factors responsible for this stimulation are discussed. This transient testicular crisis occurring at birth could affect the process of masculinization of the central nervous system of the rat.


Synthesis of 1,25-dihydroxyvitamin D in the nephrectomized pregnant rat. Pregnant rats were maintained on diets either adequate or deficient in vitamin D. On the 20th day of gestation, animals were either nephrectomized bilaterally or sham operated. Immediately therafter, four groups of nephrectomized or sham-operated pregnant rats received iv [26,27-3H]25-hydroxyvitamin D3 ([26,27-3H]25OHD3), while two groups received [1,2-3H,4-14C]D3. The animals were sacrificed 10-24 h later. The distribution of the radiolabeled metabolites of vitamin D3 was determined in extracts of maternal plasma, maternal intestinal tract, placentae, and fetuses after Sephadex LH-20 column chromatography. Both vitamin D3 and 25OHD3 crossed the placenta and entered the fetus. In anephric animals receiving [26,27-3H]-25OHD3, 24,25-dihydroxyvitamin D and a polar peak eluting in the position of 1,25-dihydroxyvitamin D [1,25(OH)2D] and 25,26-dihydroxyvitamin D were identified in extracts of maternal plasma and intestinal tracts and of placentae and fetuses. The identities of 24,25-dihydroxyvitamin D and 1,25 (OH)2D were confirmed by high pressure liquid chromatography. In rats receiving [1,2-3H,4-14C]D3, approximately 50% of the polar metabolite consisted of 1,25(OH)2D. We conclude that the anephric pregnant rat is able to synthesize 1,25(OH)2D, that the fetal portion of the feto-placental unit is the most likely site of production of this hormone, and that this metabolite of vitamin D is able to cross the placenta from the fetus to the mother.


Synergistic effect of progesterone, testosterone, and estradiol in the stimulation of chick renal 25-hydroxyvitamin D3-1alpha-hydroxylase. Castrate male chickens have low levels of renal 25-hydroxyvitamin D3-1 alpha-hydroxylase (13 pmol 1,25-dihydroxyvitamin D3/200 mg tissue . 10 min). This activity is markedly increased by the administration of 5 mg/kg estradiol and 5-20 mg/kg testosterone 24 h before in vitro measurement of the enzyme. Both hormones are required for this stimulation. The testosterone, but not estradiol, requirement for the stimulation can also be satisfied by progesterone. Progesterone (12.5 mg/kg) given in addition to estradiol and testosterone stimulates even further the 25-hydroxyvitamin D3-1 alpha-hydroxylase activity to very high levels (388 pmol 1,25-dihydroxyvitamin D3/200 MG tissue . 10 min). This is accompanied by a 3-fold increase in plasma 1,25-dihydroxyvitamin D3 (from 55 to 170 pg/ml), which provides in vivo evidence for the stimulation of the 1 alpha-hydroxylase by sex hormones in birds.


The effects of calcium and magnesium on the secretion of parathormone and parathyroid secretory protein by isolated porcine parathyroid cells. The preparation of dispersed parathyroid cells by collagenase digestion of porcine parathyroid glands, essentially as outlined by Brown et al. (Endocrinology 99: 1582, 1976), is described. The cells secrete parathormone linearly for at least 4 h of incubation and rapidly respond in inverse fashion to changes in the medium calcium and magnesium concentrations over the range 0.5-3.0 mM. In terms of inhibition of secretion, either ion was more effective in the presence of a minimum concentration of the other, indicating that calcium and magnesium affect separate cellular sites. Parathormone was identified both by immunoassay of the whole incubation medium and by its separation by polyacrylamide gels and carboxymethylcellulose chromatography. When the cells were incubated with radioactive amino acids and both the medium and cells were subsequently analyzed on gels, we found that parathyroid secretory protein as well as parathormone and some immunoactive fragments were present. Analysis of the radioactive protein contained in the cells at high and low calcium concentrations revealed that calcium decreased the formation of the secretory protein by approximately 40% without appreciably affecting the formation of proparathormone or parathormone. The secretion of both parathyroid secretory protein and parathormone were inversely proportional to the concentrations of medium calcium or magnesium. The secretion of the latter, however, was more sensitive (95% inhibition) than parathormone (40-60% inhibition) to changes in medium divalent cations. These results suggest that the synthesis, intracellular processing, or secretion of parathormone and parathyroid secretory protein utilize independent calcium- and magnesium-regulated pathways.


Euthyroidism via iodide supplementation in hereditary congenital goiter with thyroglobulin deficiency. We have studied hereditary congenital goiter in an inbred strain of goats. On a normal diet, the goats were hypothyroid and iodide taken up by the gland was released rapidly in the form of iodinated macromolecular material. This resulted in a low thyroidal iodine pool. An extremely low amount of thyroglobulin-related antigens (12 microgram/g tissue; normal, 100 mg/g tissue) was detected in the goitrous gland by RIA. Addition of 1 mg I-/day to the diet made the goats euthyroid and the serum protein-bound iodine increased to high values. Even under these conditions, however, the amount of thyroglobulin-related antigens was not significantly elevated (19 microgram/g tissue). On sucrose gradient, these antigens sedimented in the 7S region. No thyroglobulin-related antigens sedimented at 12S or 19S. Besides iodoalbumin, a heterogeneous group of abnormal iodoproteins containing T3 and T4 was observed with this high iodide intake and may have accounted for the hormone production. The abnormal iodoproteins had a molecular weight of 300,000-500,000 and a sedimentation value of about 7S. From these findings, we conclude that these goats were unable to synthesize thyroglobulin but with excess iodide, there was sufficient formation of T3 and T4 in the abnormal iodoproteins to make the animals euthyroid.


Thyroxine 5'-deiodinase activity of rat kidney: observations on activation by thiols and inhibition by propylthiouracil. Enzymatic 5'-deiodination of T4 in various tissues is known to be stimulated by thiols and inhibited by propylthiouracil (PTU). Dithiothreitol (DTT) stimulation of rat kidney T4 5'-deiodinase followed saturation kinetics. Inhibition of the enzyme by PTU (10 (-5) M) was overcome in a concentration-dependent manner by DTT, methimazole (MMI), and thiourea. Pretreatment of catalytically active kidney microsomal preparations with PTS caused persistent inhibition of enzyme activity, assayed in the absence of PTU. Similarly, injection of PTU in rats in a dosage of 5 microgram/100 g BW or greater significantly impaired T4 5'-deiodination in subsequently isolated kidney microsomal preparations. Reagents that cleave disulfide bonds (DTT and KCN), as well as the reductant, Na2S2O4, and the thioureylene, MII, partially restored activity to PTU-inactivated enzyme in a time- and concentration-dependent way. These observations suggest that PTU inhibition of T4 5'-deiodinase results from an interaction of PTU with the enzym, possibly via a PTU-enzyme disulfide which can be prevented or reversed by thiols or thioureylene agents, and raise the possibility that protein sulfhydryl groups may undergo oxidation during the reductive 5'-deiodination of L-T4.


Concentrations of triiodo-L-thyronine in the plasma and tissues of normal rats, as determined by radioimmunoassay: comparison with results obtained by an isotopic equilibrium technique. The concentrations of T3 (3',3,5-triiodo-L-thyronine) have been determined by RIA in plasma, liver, kidney, heart, muscle, brain, and lungs of normal male rats. The method involves homogenization, addition of a high specific activity labeled T3 tracer, extraction with ethanol, separation by paper chromatography, elution of the labeled T3 spot, evaporation of an aliquot, and assay of its T3 content by a highly sensitive RIA. In order to validate the results thus obtained, they were compared with the T3 concentrations determined for the same samples using an isotopic equilibrium technique. The data obtained by RIA were in close agreement with those derived from the isotopic equilibrium technique, whenever the latter could be applied accurately. The present RIA method permits the determination of T3 in tissues without imposing the well known limitations of the isotopic equilibrium technique. The concentration of T3 was higher in the kidney than in the liver. In kidney, liver, brain, and lung, it was higher than the concentration in plasma. The concentration of T3 in heart was the same as that in plasma. Similarities and differences with respect to data reported by others are discussed.


The effect of hemorrhage and hypertonic saline upon plasma oxytocin and arginine vasopressin in conscious dogs. Sensitive and highly specific RIAs for arginine vasopressin (AVP) and oxytocin (OT) were utilized to assess the specificity of neurohypophyseal hormone release after hemorrhage or infusion of hypertonic saline to trained conscious dogs. Phlebotomy of 12.5 and 25 ml/kg produced increases in plasma AVP from 1.0 +/- 0.2 to 7.8 +/- 2.1 and 41.6 +/- 9.7 (SEM) microunit/ml respectively, and both responses differed significantly from values in control experiments (P less than 0.01 after the first phlebotomy and P less than 0.001 after the second phlebotomy). Plasma OT concentrations rose from baseline values of 1.1 +/- 0.4 to 3.3 +/- 0.6 and 8.3 +/- 1.7 microunit/ml (P less than 0.005 and P less than 0.001 compared to controls); plasma osmolality and sodium concentrations were unchanged. Both log AVP and log OT were highly correlated with the quantity of blood removed (r = 0.92 and -0.82, each P less than 0.001). Infusion of hypertonic (20g/dl) NaCl (3.4 meq/kg) over 20 min caused plasma osmolality and sodium to rise from 304 +/- 1.0 mosm/kg and 143 +/- 3.0 meq/liter to 316 +/- 1.0 mosm/kg and 150 +/- 3.0 meq/liter (each P less than 0.001). Plasma AVP rose from 1.5 +/- 0.2 to 2.4 +/- 0.2 microunit/ml (P less than 0.0025) and OT rose from 1.2 +/- 0.5 to 2.6 +/- 0.7 microunit/ml (P less than 0.005). The stimulus response ratios (change in log hormone concentration divided by the rise in plasma osmolality) were comparable for both hormones (0.024 +/- 0.006 for AVP and 0.031 +/- 0.008 for OT; P less than 0.4). The data indicate that hemorrhage or hypertonic saline stimulate release of both AVP and OT. After hemorrhage, there is greater stimulation of AVP than OT, whereas there is comparable stimulation of both peptides after hypertonic saline.


Acute and chronic fluctuations of immunoreactive and biologically active plasma calcitonin in the rat. Using a sensitive calcitonin (CT) immunoassay and a newly developed bioassay capable of detecting 0.025 MRC mU CT, we have studied acute and chronic plasma CT fluctuations in male and female rats. Immunoassay of serial plasma samples revealed progressive increases in plasma CT concentrations during aging; female rats have higher CT concentrations than age-matched males. Acute periodic CT fluctuations were discovered by immunoassay of plasmas obtained at 3-h intervals; the greatest values occurred just before and during feeding. Fed rats have higher CT than starved rats. We have used immunoadsorbent chromatography to concentrate specifically CT moieties from large volumes of plasma for concurrent immunoassay and bioassay measurements of circulating CT. These concurrent measurements of immunoextracted plasma CT demonstrate that for normal rats, our immunoassay measurements correspond to bioassay measurements. In 1-yr-old rats on a regulated feeding schedule, the biological (hypocalcemic) activity of CT recovered from 15 ml peripheral plasma ranged from less than 0.15 mU in starved males to 0.78 mU in feeding females. We conclude that biologically active CT circulates in normal rats and that the blood concentration of biologically active CT progressively increases during somatosexual maturation, being highest in old females, and increases acutely just before and during feeding.


Mechanism of action of thioureylene antithyroid drugs: factors affecting intrathyroidal metabolism of propylthiouracil and methimazole in rats. Experiments were performed with rats to test the physiological significance of a previously proposed mechanism of action of thioureylene antithyroid drugs, which had been derived from results obtained with a model system containing purified thyroid peroxidase. Two features of the previously proposed scheme were tested:1) the effects of drug dosage and 2) the effects of iodine deficiency. In the dosage experiments, rats were injected with graded doses of [35S]PTU (0.18-59 mumol or [35S]mmi (0.16-18 mumol). Thyroid glands were removed 1 and 6--8 h later and 35S distribution in the homogenates was determined by paper chromatography. Serum samples were also analyzed by the same procedure. From the measured 35S activity in the various components and from the known specific activity of the injected drugs, it was possible to calculate thyroidal concentrations of unchanged drug and drug metabolites. At low doses, thyroidal concentrations of unchanged 6-propyl-2-thiouracil (PTU) and 1-methyl-2-mercaptoimidazole (MM) significantly exceeded their concentrations in serum, as reported by previous investigators. A major new finding in the present investigation was the observation that intrathyroidal metabolism of PTU and MMI is greatly affected by dosage. Marked inhibition of intrathyroidal drug metabolism was observed at 6-8 when the dosage was increased from 5.9 to 18 mumol for [35S]PTU and from 0.88 to 2.2 mumol for [35S]MMI (per 200 g rat). These findings demonstrate that with increasing dosage, PTU and MMI inhibit their own intrathyroidal metabolism. These dosage effects are similar to results previously reported for in vitro oxidation of PTU and MMI by the thyroid peroxidase system, and they offer support for the physiological significance of the previously proposed scheme. Further evidence for the physiological validity of this scheme was obtained in the experiments with iodine-deficient rats. As predicted from the in vitro findings, intrathyroidal metabolism of [35S]PTU and [35S]MMI was markedly reduced in rats on low iodine diet.


Spontaneous dissociation of human pituitary luteinizing hormone in solution. Aliquots of a solution of highly purified human pituitary LH (hLH) were incubated with variations in temperature and time. The incubates were chromatographed on Sephadex G-100 as well as on DEAE-Sephadex A25. The column effluents were assayed in radioligand assay and in specific hLH alpha- and hLH beta-RIA systems. The results indicate that there is spontaneous dissociation of hLH at elevated temperatures under otherwise "normal" conditions concerning, for example, pH and ionic strength. The degree of dissociation is both time and temperature dependent. This dissociation is not due to proteolytic enzymes. It is concluded that one should be alert when using hLH subunit RIA systems at elevated temperatures for measuring hLH levels, e.g. in clinical samples, because artificial high levels may be obtained.


The effects of dietary carbohydrate content on insulin binding and glucose metabolism by isolated rat adipocytes. The effects of changes in the amount of dietary carbohydrate (CHO) on cellular insulin and glucose metabolism have been assessed in rat adipocytes. Feeding animals a 67% CHO (fat-free) diet resulted in decreased insulin binding but enhanced activity of both the glucose transport system and intracellular pathways of glucose metabolism. Feeding rats a 67% fat (CHO-free) diet resulted in decreased insulin receptors as well as decreased activity of the glucose transport system and intracellular glucose metabolism. Therefore, the in vivo insulin resistance caused by a high fat, low CHO diet seems to be adequately explained, since all aspects of insulin's cellular action were depressed. On the other hand, at first approximation, the increased in vivo insulin response caused by a high CHO diet appears contradictory to the observed decrease in insulin binding. However, a probable explanation for this apparent paradox is provided by the enhanced activity of the cellular insulin effector systems distal to the insulin receptor. Therefore, the increased in vivo insulin responsiveness after high CHO feedings is most likely due to post receptor increases in various aspects of glucose metabolism.


Phylogenetic distribution of aromatase and other androgen-converting enzymes in the central nervous system. Metabolism of [3H]androstenedione was studied in brain tissue homogenates of opossum, bird, snake, sea turtle, urodele amphibian, teleost, shark, skate, hagfish, and lobster. Estrone, 17 beta-estradiol, or 17 alpha-estradiol was formed by central neural tissues of all species, with the exception of the opossum, hagfish, and lobster. Aromatase activity was concentrated in the forebrain, although some estrogen was synthesized by mid- or hindbrain homogenates of two lower vertebrates (teleost and skate) and the newly hatched chick. 5 alpha-Androstanedione (5 alpha-androstane-3,17-dione) or 5 alpha-dihydrotestosterone were products of metabolism in several nonmammalian vertebrates and in the invertebrate central nervous system also. 5 alpha-Reductase was found in all major brain divisions. These and previously reported comparative studies indicate that the ability to aromatize and otherwise transform androgen substrates is a primitive characteristic of the brain that has been widely conserved phylogenetically.


Blood capillary enlargement during the development of thyroid hyperplasia in the rat. To study blood capillary growth in the hyperplastic thyroid gland, rats were fed 0.25% thiouracil in a low iodine diet for time intervals up to 100 days. Thyroids were fixed by vascular perfusion and embeded in Epon. Whole lobes were sectioned from pole to pole and slides were prepared of sections every 0.3 mm. Capillaries were clearly enlarged by 3 days and they enlarged progressively thereafter. By 3 days, the cells of many neighboring capillaries came into close apposition and from this time on, there was evidence of fusion of capillary walls in the form of partial septa in the capillary lumens. Fusion continued until 20 days, when follicles were almost completely surrounded by a continuous endothelial sheet and unfused capillary walls were separated by connective tissue. The vascular pattern around peripheral follicles changed in a way similar to interior follicles, except that in places, capillaries were gradually excluded from the space between epithelium and thyroid capsule. Vascular enlargement was restricted to the thyroid blood vessels. There was no obvious enlargement of the blood capillaries of the parathyroid despite its close proximity to the thyroid.


The measurement of steroid glucuronides in urine from mice to monitor gonadal function. I. Pregnanediol-3 alpha-glucuronide as an index of progestogen output. An attempt has been made to assess the output of progesterone in mice by measuring the concentration of pregnanediol-3 alpha-glucuronide (PdGl in serial samples of unextracted urine. Longitudinal studies with 95 animals have shown that sufficient urine (greater than 40 microliter) can be obtained from individual animals (80% success rate) without stress every day or at intervals of 2 h. The sc administration of 50 microgram progesterone in lauric acid ethyl ester resulted in a 9-fold increase in the concentration of urinary PdGl (within 4 h) and a significantly elevated output for the next 26 h. During the induction of superovulation with PMS and hCG, the values of PdGl increased significantly (P less than 0.0005; by Student's t test) from 2.08 +/- 0.97 to 3.99 +/- 2.55 ng/ml (mean +/- SD) at the time of corpus luteum formation. There was a good correlation (r = 0.84; n = 154) between the values expressed as nanograms per ml urine and nanograms per mg creatinine. The results demonstrate that the concentration of PdGl in serial samples of urine may be used as an index of gonadal function in female mice.


Characterization and application of a radioimmunoassay for reduced, carboxymethylated human luteinizing hormone alpha-subunit. We have established a double antibody RIA using a rabbit antiserum prepared against reduced, carboxymethylated (RCXM) human LH alpha-subunit, with RCXM-alpha as tracer and standard. This antiserum did not cross-react with any native gonadotropins or subunit, and reacted only weakly with RCXM-alpha. A tryptic digest of RCXM alpha-subunit was completely reactive, while chymotryptic digestion abolished all immunoreactivity. By testing with separate tryptic fragments, the recognition site could be localized to a segment close to the amino-terminus of the peptide chain. When applied to measurement of serum and urine, an immunoreactive species, parallel to RCXM alpha-subunit by serial dilution, was found in concentrations of 1-2 ng/ml in serum and 3-4 ng/ml in urine. Similar levels of the immunoreactive component were found in conditions of elevated gonadotropins (e.g. pregnancy) as well as gonadotropin deficiency(panhypopituitarism and Kallmann's syndrome). After stimulation with LHRH, no rise was noted at times up to 6 h despite the fact that both LH and LH-alpha were elevated. The data indicate that the sequence-specific antiserum may be detecting an immunoreactive form of alpha-subunit of LH whose kinetics of appearance and disappearance differs from those of the native subunit.


Lipolytic response of rat adipocytes to epinephrine: effect of age and cell size. Isolated fat cells from 3, 12 and 28 month old rats were compared intheir lipolytic response to various doses of L-epinephrine. With increasing age a progressive decline in the response occurred when comparing rats with unmatched mean adipocyte diameters. However, this apparently age-related decrease was no longer evident if the diameters were matched since the 28 month old animals had a lipolytic response less than the 3 month old rats but greater than the 12 month olds. Body weight differences between these ages may account for these observations. The biphasic dose response curve to hormone stimulation in the 3 and 12 month olds was monophasic at 28 months. Within each age group the initial lag in glycerol release decreased and the lipolytic response increased as mean cell size increased. The rate of hormone stimulated glycerol release varied inversely with incubations of 3,700 to 25,000 cells/ml and aging had no effect on this parameter. DNA content per fat cell remained constant with age.


Use of the Satz-Mogel abbreviated WAIS with hospitalized geriatric patients. The equivalency of standard and Satz-Mogel WAIS scales for psychiatrically hospitalized geriatric patients was studied using a matched control and experimental group, test-retest design. On the Verbal, Performance, Full Scale, and subtest scales the two forms had distributions whose central tendencies and variances were statistically equivalent. Score reliability for the two forms was shown by the finding of only one significant test-retest correlational difference between corresponding scales for the two groups and by difference-score variances which generally pointed to only a slight statistical tendency of the short form to generate larger differences between test and re-test scores.


The interrelationship of memory functions in a nursing home population. Memory functioning was assessed in a group of thirty nursing home residents to determine the level of functioning and the interrelationship of memory processes and age in this population. Nine different types of memory processes were measured. Results indicated that memory functions in this population were interrelated to a greater extent than in community based elderly populations, yet not to as great an extent as suggested in other more impaired groups. On the other hand, while 21 of the 36 correlations of scores on the tests of memory were statistically significant, the greatest amount of variance accounted for between these test scores was only 55%. This result was interpreted to indicate that the memory functions assessed in this nursing home population were non-unitary in nature. The implications of these findings for memory theory and for the practitioner are discussed.


Problem-solving as a function of age, sex and the role appropriateness of the problem content. The purpose of this study was to investigate problem-solving ability as a function of age, sex and problem content by using 20 problems chosen from the problem-solving literature. The problems were administered without time limits to 8 males and 8 females in each of three age groups: 20--30, 40--50, 60--70. Analysis revealed that only age influenced performance with the middle-age group scoring significantly higher than the other groups. Analysis of the time required by each age group to solve the problems showed the young group required significantly less time than the other groups. Finally, the young group was seen to make more errors of commission while the older group made more errors of omission.


Influence of contextual variables on blood pressure in the elderly. This research evaluated determinants of blood pressure in elderly subjects. Measurements were obtained from 30 subjects in three contexts; in the home measured by the subject, in the home measured by the experimenter, and in a psychophysiological laboratory measured by the experimenter. Four measurements were obtained in the two home conditions and two were obtained in the laboratory condition. For systolic blood pressure, the effects of condition, repeated measurement, and order of treatment presentation were significant. For diastolic blood pressure, the effect of condition was significant. A comparison of sample variances revealed greater variances for systolic blood pressure. It was concluded that initial blood pressure measurements obtained in a laboratory should be regarded as distinct from those obtained later, as the early measurements may be subject to elevation imposed by the context. Due to differing patterns of results for systolic and diastolic pressures as well as differences in variability, it was concluded that there exist conceptual problems with a construct such as mean arterial pressure.


The effect of protein-free diet on blood pressure in the Wistar rat. The relationship between blood pressure (BP) and an 18 day protein free diet (PFD) was studied in unanesthetized male Wistar rats beginning at 20 weeks of age. Following cessation of the 18 day diet, BP was monitored for 8 weeks. Both the PFD animals and a control diet (CD) group showed a reduction in BP from 20 weeks to 30 weeks. Reduction in BP for PFD animals was 3 times that of the CD animals across the diet period. The authors caution the reader in terms of generalizing across strains for this effect and suggest that a greater data base is needed before a definite statement can be made concerning the effects of a protein free diet on BP.


Studies on the pepsinogens of human gastric mucosal extracts. 1. Electrophoretic separation of proteases from human gastric mucosal extracts of five patients with gastric ulcer, one with duodenal ulcer and three with gastric cancer were investigated by agar-gel electrophoresis at pH 8.3 and pH 5.0. 2. In the fundic mucosal study, there were seven faster moving proteases in all nine cases, but the slowest moving protease showed a slightly different picture in each case. In the antral mucosal study, two of eight cases showed mainly group II pepsinogens, seven of nine cases, however, showed the same results as in the fundic mucosal study. 3. In the cases of the nine mucosal extracts activated at pH 1.5 or pH 4.0, they all showed the same electrophoretic separation at each pH level. At these two pH levels, however, quite different electrophoretic patterns were observed. The presence of pepsin 3 appeared to diminish at the higher levels of pH, although that of pepsin 5 and pepsin 7 appeared to increase at pH 4.0 and above. Pepsin 6 appeared for the first time at pH 4.0 and existed at higher pH levels. 4. We thus conclude that electrophoretic patterns of pepsins in the gastric mucosal extracts are changeable depending on the pH level of the incubating medium, and further that diversity of pepsins in gastric juices may also depend on the pH level of gastric juices.


Gastric mucosal barrier in the rats fed with protein deficient diet or treated with carbon tetrachloride. The effects of protein deficient diet and liver damage on the gastric mucosal barrier were studied in 32 Sprague-Dawley rats. The animals were divided into 4 groups according to their dietary regimens, CCl4 induced liver damage and/or serotonin administration. Group 1 (control) was fed standard rat chow. Group II was fed a nonprotein diet for 2 weeks. Group III and IV were fed standard rat chow and given 1 ml of CCl4 per/Kg body weight intraperitoneally twice weekly for 12 weeks. Rats in Group IV were also injected with 20mg per/Kg of serotonin intraperitoneally 30 minutes prior to surgery. After pyloric ligation, an acid test solution composed of 100 mM HCl, 10mM NaCl, 5mM KCl and 5g per litre of PEG was instilled into the stomach and fluxes of Na +, K +, H + and Cl-ions across the gastric mucosa were measured. Compared to Group I, rats in Group II, III and IV demonstrated an increased net negative hydrogen flux (p less than 0.05). An increased net negative chloride flux (p less than 0.05) was also demonstrated in Group II and IV, but no increase was noted in Group III. There were no significant differences in fluxes of sodium and potassium ions. As mentioned above, a lack of protein in the diet, liver damage or both, renders the gastric mucosa of the rat more susceptible to injury. In the gastric mucosa of these rats, there have occurred more increase in the negative net fluxes of hydrogen and chloride ion, which may indicate the reduction of defence mechanism against a mucosal damage.


A hydraulic behavior of the mucosal structure of the intramural common bile duct. An experimental study. In the intramural portion of the common bile duct in the dog, the lumen is occluded by the mucosal folds which are pointed to the direction of the ductal orifice. Luminal occlusion by the folds becomes more marked from the halfway of the portion as judged from the duodenal muscle layers. A pressure study using the pressure ramp apparatus suggested that the mucosal structure plays some role in generating the passage resistance to bile floow and in the prevention of regurgitation of duodenal content.


Reserve capacity of bicarbonate secretion in chronic pancreatitis. When secretin was given by continuous intravenous infusion in the control subjects, the dose of secretin inducing maximal bicarbonate output was found to be around 6.0 CHR U/kg/hr. Then the pancreatic exocrine secretory response to sequential standard (1.2 CHR U/kg/hr) and augmented (6.0 CHR U/kg/hr) dose of secretin was studied in the controls, in patients with chronic pancreatitis and in its suspected cases. This new method for exocrine pancreatic function did not offer advantage for the diagnosis of well established chronic pancreatitis. But from the results obtained in suspected chronic pancreatitis it was supposed that the decline of increasing rate of bicarbonate output with augmentation of dose and the decrease of response to augmented dose of secretin might be one of functional disorders occurred in the early stage of chronic pancreatitis.


Analysis of human pure pancreatic juice in chronic pancreatitis and cancer of the pancreas. Pure pancreatic juice was collected from 8 control subjects, 12 patients with chronic pancreatitis and 4 patients with cancer of the pancreas by endoscopic retrograde cannulation of the papilla. Samples were collected at 1 minute intervals for 20 minutes after rapid intravenous injection of secretin (Eisai, 1 U/kg) and for 10 minutes after rapid intravenous injection of CCK-PZ (Boots, 1 U/kg). Determinations of volume, bicarbonate concentration and three hydrolases (amylase, chymotrypsinogen and lipase) were made. Our tentative conclusions are (1) pancreatic enzymes are likely to be affected one after another, not in parallel fashing, in chronic pancreatitis and in cancer of the pancreas, (2) bicarbonate concentration and chymotrypsinogen or lipase are most susceptible in chronic pancreatitis and lipase secretion seems to be more susceptible than other parameters in cancer of the pancreas. Amylase is the least affected enzyme in both pancreatic diseases, and (3) determinations of chymotrypsinogen and/or lipase should be preferably performed among hydrolytic enzymes in the evaluation of exocrine pancreatic function in chronic pancreatitis and cancer of the pancreas.


Effect of exogenously administered glucagon on plasma glucose levels in totally depancreatized dogs. Glucagon was administered exogenously via a subcutaneous route to totally depancreatized adult mongrel dogs and studies were made with major emphasis on glucagon effect on the plasma glucose levels. 1. In the totally depancreatized dogs, the plasma glucose levels determined 90 minutes after glucagon injection (40 micrograms/kg s.c.). were compared with the pretreatment fasting plasma glucose levels. The rate of increase in the plasma glucose levels was 5.13 +/- 0.48 times (M +/- SEM) in dogs with low pretreatment level (lower than 100 mg/dl). In dogs with higher pretreatment levels (100-400 mg/dl), the increase was 1.62 +/- 0.40 times. And in dogs with the pretreatment levels higher than 400 mg/dl, the value was 0.90 +/- .07 times. 2. Ninety minutes after regular insulin injection (0.25 U/kg i.v.), glucagon was administered (40 micrograms/kg s.c.), and the changes in the plasma glucose levels were determined. 3. In totally depancreatized dogs, a transient increase in the plasma insulin level was noted when glucagon was administered (40 micrograms/kg s.c.) under infusion of a mixture of glucose and insulin. 4. There was no significant difference in the rate of disappearance of glucagon from the blood between normal and totally depancreatized dogs. 5. It is considered that glucagon would be useful for the treatment of hypoglycemia encountered after total pancreatectomy.


Clinical significance of serum bile acid measurement in liver diseases. To determine the clinical significance of serum bile acid measurements, changes in the serum bile acid composition in liver diseases and endogenous bile acid clearance due to test meal loads were investigated. In the case of changes in the serum bile acid composition, a characteristic pattern of a remarkable increase of chenodeoxycholic acid (CDCA) was found in fulminant hepatitis. In patients with acute hepatitis, increases in CDCA were somewhat greater than those of cholic acid (CA) and there was tendency for these changes to precede changes in other liver function tests. In cases of extrahepatic obstructive jaundice, the CA/CDCA ratio was a large value exceeding 1.0. In investigations of endogenous bile acid clearance, serum bile acid concentration two hours after the text meal load clearly reflected the hepatic disorder and it was useful in differentiating between active and inactive form in chronic hepatitis and compensation and decompensation in liver cirrhosis.


Serum glycoproteins in the liver diseases. V. Desialylated glycoproteins in chronic hepatitis. Serum desialylated glycoprotein level was tested for chronic hepatitic patients. The level was significantly elevated in patients with chronic aggressive hepatitis but not in chronic persistent hepatitis comparing to normal subjects. In chronic aggressive hepatitis, severe type (2B), serum desialylated glycoprotein levels were significantly enhanced but not in moderate type (2A) when compared to chronic persistent hepatitis. Sera taken serially from patients with chronic aggressive hepatitis, severe type (2B), demonstrated a slight correlation between circulating desialylated glycoprotein level and serum glutamic-pyruvic transaminase activity.


Serum glycoproteins in the liver diseases. VI. The presence of desialylated glycoprotein binding activity in particulate fraction of human liver homogenate. The human liver as well as rat liver particulate fraction was determined to have an ability to bind desialylated alpha 1-acid glycoprotein. The binding activity of human liver was the same order of the rat one. A more increased amount of binding of desialylated glycoprotein was found in a new born liver than an adult one. Serum obtained from a cirrhotic patient inhibited the binding. The sucrose density gradient centrifugation revealed that the activity located partly in fractions in which a membrane enzyme, alkaline phosphatase, was detected. The binding activity was a linear function of concentration of human liver particulate fraction added to incubation mixture.


[Free transplantation of a fibula with epiphysis]. Problems of free bone transplantation, as well as those of bone transplantation by microvascular anastomoses are exemplified by a case of free fibula transplantation--the epiphysis being conserved--by microvascular anastomoses. If revascularisation of the bone transplant is immediately achieved, the chance for survival of bone tissue is improved and there is a chance that the epiphysis will retain the capacity to grow. By multiple surgical interventions the stability of the abnormally mobile forearm was reestablished and considerable lengthening of the shortened skeleton was achieved. By tendon and nerve transplantations simple grasp could be restored to the hand which originally was without function.


[Significance of ulnar ligament injuries in typical radius fractures]. In 20 patients with COLLES' fractures, stress-films of the wrist demonstrated that without fracture of the ulnar styloid ruptures of the ulnar ligaments are possible, and lead to increased radial abduction of the carpus. This instability together with interposition of the ruptured soft tissue produces a tendency to radial subluxation of the hand, in spite of good alignment of the fragments. In conclusion, we suggest that in younger patients closed reduction should be stabilized by means of percutaneous Kirschner-wires and that the interposed soft tissue should be excised.


[Arthrodeses of the small finger joints. Clinical studies of results with Kirschner's wire and tension arthrodeses]. An analysis of a series of 41 consecutive arthrodeses of finger-joints on 39 patients is given. Functional and cosmetic results were satisfactory. We prefer the tension band arthrodesis for its uncomplicated aftercare, the brief period of morbidity and the short period of absence from work.


[Ambulatory treatment of extensor-tendon injury in general surgery]. Extensor tendon injuries are mostly treated by younger general surgeons. Good follow-up results in the zone 2, 3, 4 and 6 of VERDAN are observed only 6 to 17 percent (fig. 1), which may be explained by: 1. the complicated anatomy of the extensor tendon in zone 2 to 4, 2. lack of attention to handsurgical principles, 3. infections in up to 40 per cent, which appear especially in connection with extensive soft tissue damage, 4. posttraumatic arthrosis (fig. 3) caused by lesions of the finger-joints or temporary KIRSCHNER wire fixation. The highest restriction of movement is found in the finger-joint distal to the injury (fig. 2.) The degree of flexion deficit in all finger-joints always exceeds the degree of extension deficit (fig. 4). The extension deficit alone is, therefore, not a satisfactory criterion in follow-up. The use of KIRSCHNER wire fixation by the inexperienced and the adoption of conservation therapy for zones 1 and 2 cannot be recommended.


Variations of palmaris longus.

Variations of palmaris longus. Although variations of palmaris longus muscle are described in anatomical text books, they are seen rather rarely in practice. Within the last five years of hand surgery we came across threee different cases of such variations described in the above text. We believe that every surgeon must be aware of them, since this, otherwise unimportant muscle, provides a very useful graft in tendon surgery.


[Specific fibre compositon of human hand and arm muscles]. The authors examined the fiber composition of the finger, hand, and arm muscles. It is established that the type of fiber composition is not influenced by the mechanical employment of the hand- and arm muscles. The fiber composition of the finger muscles, however, is different in the two hands, in that the amount of fiber type II is significantly higher than that of the fiber type I in the dominant hand. In case of the non-dominant hand the fiber type I is predominant.


[Hanging legs for sural nerve excision (author's transl)]. The sural nerve is widely used as a graft in autologous nerve transplantation. In major operations on the upper extremities and the brachial plexus the lateral or ventral position of the patient most convenient for harvesting the graft is impossible. It is, however, easy to excise the sural nerve if the legs are hanging.


Computed tomography of brains of epileptic children. 1) Most of the intractable epileptic children showed abnormal EEG and abnormal CT findings. 2) The abnormal side of CT findings of focal epilepsy corresponded with the abnormal side of clinical manifestations and EEG findings. 3) CT findings of the brains of patients with infantile spasms exhibited cerebral cortical atrophy. 4) CT findings of the brains of the other epileptic types were not related to clinical manifestations or EEG findings.


Long-term prognosis on recurrence of seizures among children with epilepsy after drug withdrawal-elimination. The long-term prognosis of 110 children after withdrawal-elimination of the drugs on the basis of our rigid criteria was analyzed. The 12 cases (10.9%) of 110 patients experienced recurrences, which occurred between three months to three years after drug elimination, but there were no recurrences later than three years to 10 years after drug elimination. The asymmetry in the EEG during the first two to three years after drug elimination appeared in 6.4% and seizure discharge appeared in 17.1%. But no asymmetry nor seizure discharge was found in EEG later than three years after drug elimination.


Drug treatment: factors contributing to high risks in institutions. Because of the widerspread use of drugs in the treatment of exceptional children, investigators are currently studying the efficacy, suitability and safety of the drugs employed. This paper deals with an aspect of pharmacological management which has been largely neglected in the literature: the administration of prescribed drugs. Focusing on the institutional setting, the following three factors contributing to high risk of drug error or misuse, are delineated: (1) Staff training and sophistication, (2) Number and complexity of drugs employed and (3) Vulnerability of the exceptional child. An attempt is made to state and clarify these issues, to report some preliminary programs which appear to be effective, and to offer some concrete suggestions for persons who are involved in the pharmacological management of exceptional children.


Vibratory perception by deaf children.

Vibratory perception by deaf children. Audiologists and educators of the deaf have become interested in vibratory perception of speech because: (1) research suggests that profoundly deaf children feel rather than hear amplified speech through their ears, and educators must help them to use this acoustic (vibratory) speech information; and (2) vibratory transducers already are used in many classrooms for deaf children to provide supplementary speech input, and educators must learn how to present vibratory stimuli most effectively for perceptual learning. Vibration provides mainly the gross time-intensity information in speech. This paper describes the variety of speech cues that are available through the vibratory sense, for example, number of syllables; syllable rate, stress, and onset/decay; pause; and roughness. An optical analog (tracings from a storage oscilloscope) is used to show the type of information available to deaf persons through vibration. Deaf children are able to perform not only closed-set recognition tasks but also can learn to identify general characteristics of vibratory speech patterns. Although vibratory perception alone is limited for communication, vibratory input can serve as a supplement to lipreading and also as a speech-training aid for profoundly deaf persons.


A discriminatory analysis based on dichotomized Rorschach scores of diabetic children. 16 diabetic children and 16 non-diabetic children were tested with the Rorschach. 183 dichotomized items were obtained. From the scores of these items a discriminant anlysis based on the weighted H index was obtained and applied to a new group. This group also consisted of 16 diabetic and 16 non-diabetic children. Using the discriminant analysis, all but one of the children in the new group were correctly classified. It is interesting to notice that "penetration" a Rorschach item indicating a disturbed body-image, has the highest absolute value of the D-estimate. A disturbed body-image development is a common feature in the diabetic group.


A study of the play behavior of retarded children. Piaget, Almy and Peller have pointed to the necessity of play for cognitive development. Earlier, Lehman and Witty, Boyton and Ford, Horne and Philleo. Tilton, Ottinger and Weiner conducted studies on play in cognitively disturbed children. Hetzer and Inhelder show that the retarded child annot utilize his play area because of poor imagination and lack of expressive skills. Many play activities have a perseverating character. They cannot make sufficient use of the possibilities inherent in the toys presented to them. Uncontrolled drives inhibit creative and constructive play. Often, a plan d'attaque for play is lacking. Following on the heels of earlier studies, systematic play observations of 38 retarded children were made using ten observation categories. In Table II the results are shown of the way in which the child uses a toy. The play behavior of the retarded child is predominated by a great need to explore, experiment and move. He hardly has a chance to use toys in a creative way resulting in a play endproduct. The choice of toys is given in Table III. Boys had a particular interest in vehicles and environmental material, girls in dolls. According to expectation, the level of play behavior (Table IV) and the scores on an intelligence test (HAWIK) appeared to positively correlate with each other. This was also true for the correlations between the subtest scores and play behavior, with the exception of similarities and block design. Also, the variation in the exhibited play behavior correlated positively with the measured IQ's. In view of the correlations found, there are indications that imitation play is important for emotional and social behavior. Older study results, which showed a connection between an identification score and imitation play seem to be confirmed in retarded children, too. For the practical situation in child-rearing and education, the study results point to the necessity of bringing the retarded child into contact with as many different toys as possible.


[Communicative and social behavior of speech disordered children]. The spheres covering behaviour disorders, social behaviour and communicative behaviour of speech impaired pupils which until now have been analyzed on a more theoretical level, ought to be studied using psychometric testing procedures and an esperimental observational situation in order to gain base data with which to set up a concrete catalogue of aims (learning program) based on the deficits thereby obtained. The study took place at the special school in Esslinger-Berkheim (Baden-Wurttemberg). By taking into account relevant specialized literature and the results of other studies, the following general hypotheses were advanced, namely, that the communication of speech handicapped children is troubled in respect of its content and relation, and that their social behaviour shows more egoistic than cooperative features. In order to determine social motivations and attitudes, we used Muller's "Social Motivation Test" (SMT) and Jorger's "Group test for the social attitude" (S-E-T). Due to the inconsistency between the attitudes measured by means of psychometric methods and the sbusequent free and genuine behaviour, an observational situation was developed during which the pupils, either in pairs or in groups of four and using puppets, took turns in thinking up a story, discussing the plot, roles, etc. and finally putting on the play. The whole was then analyzed by means of tape recordings and film shots, the interaction of the communicating partners being analyzed and categorized in two separate assessment stages: communicative behaviour and social behaviour. The pragmatic axioms of P. Watzlawick, the communication researcher, functioned as theoretical background. Flanders's linear time diagram was used as assessment system. Communicative and social learning aims were prepared in accordance with confirming hypotheses to enable a "preliminary area" for the practical work in (special) education to be defined. In addition, a rough outline was made of the conditional areas pertaining to social and communicative education of the speech impaired for the purpose of carrying out a systematic change.


Socio-cultural and clinical determinants of symptomatology in obsessional neurosis. Eighty-two obsessional neurotics were studied from a phenomenological viewpoint in order to unmask the clinical and socio-cultural determinants of symptom-choice in this disorder. The form of obsessions and compulsions seemed to be affected primarily by intrinsic factors (age, sex, I.Q.) while their content was affected equally, if not more, by extrinsic factors (religion, locality, social class). Patient's age at the onset of illness seemed to be an extremely relevant factor insofar as it affected both the form and the content of symptoms. Some socio-cultural explanations have been offered these findings. The data is important insofar as it provides a baseline for cross-cultural studies of the phenomenology of obsessional illness.


Obsessional neurosis, marriage, sex and fertility: some transcultural comparisons. In a study of 82 obsessional neurotics, it was found that Indian obsessives, unlike their counterparts in other countries, do not display a higher than expected rate of celibacy, bachelorhood, and low fertility. Some socio-cultural explanations have been offered for these findings.


Sociocultural factors in hallucinations. Sociocultural factors affect both the definition and the sense organs involved in hallucinations. It is suggested that, in addition to the importance of audition in communication on the human level, other sociocultural factors may affect the choice of sense organs in the expression of hallucinatory experience. As compared with non-Western societies, Western attitudes consider hallucinations more shameful and frightening (symptoms of mental illness) and this tend to be more liable to concealment and chronicity. It is proposed that the psychoanalytical approached to the interpretation of dreams or behavioural techniques could be used to overcome the concomitants of Western attitudes toward hallucinations.


Cultural aspects of psychiatric clinic utilization a cross-cultural study in Hawaii. Data was obtained by ethnic status from 411 outpatients at a psychiatric clinic in Honolulu, Hawaii, and were then analyzed according to demographic variables, welfare status, source of referral, primary compliants or symptoms, diagnosis, and duration of treatment received. Clinic utilization was highly related to ethnicity, with Caucasians highly over-represented in proportion to the population, and other groups, especially Japanese, being greatly under-represented. The Caucasians were more likely to be self-referred, to have subjective symptoms of anxiety and depression, and to receive a neurotic diagnosis. The Japanese, and to some extent all other groups, were more often referred after a crisis or severe mental illness, displayed more socially disruptive symptoms, and had a higher percentage of schizophrenic diagnoses. Ethnicity was thus highly related to utilization of mental health services; however, once entry into the system was made, review of therapist case loads and analysis of duration of treatment revealed no ethnic difference in the clinic's response to patients.


Mental illness and the family in America and India. The relationship of family support systems to emotional problems is presented from a transcultural perspective in the light of differences in the types of patients seen at one American and two Indian clinics. The American cultural emphasis on individuation and role adequacy is reflected in a much higher incidence of adjustment reactions and personality disorders among American patients. The positive view of mutuality and interdependence among Indians helps decrease the need for psychiatric help for these problems so long as the individual is an integral part of the family. Separation from the supportive role of the family, however, brings about a sharp increase in the incidence of these problems.


Surface features of Sézary cells. A scanning electron microscopy study. The surface features of circulating cells from three patients with Sézary syndrome were examined by scanning electron microscopy. The Sézary cells were mostly spherical and displayed varying numbers of microvilli. Most cells had moderately to markedly villous surfaces and had surface features similar to circulating leukemic lymphocytes isolated from patients with chronic lymphocytic leukemia. Some cells were more irregular in shape, while others displayed clusters of polarized microvilli and small uropods. Similar findings were seen in thin sections of cells on transmission electron microscopy.


Hodgkin's disease and subsequent chronic lymphocytic leukemia in a patient with breast carcinoma. This report deals with an unusual case of a patient with four primary tumors. Hodgkin's disease developed in an elderly woman 21 years after she was treated for carcinoma of the breast by surgery and irradiation. Chronic lymphocytic leukemia and a liposarcoma of the soft tissues developed two years after the appearance of Hodgkin's lymphoma. The coexistence of four primary tumors in the same patient is rare; the simultaneous occurrence of Hodgkin's lymphoma and lymphocytic leukemia is in itself a rare association  and is probably a chance finding. The development of these neoplasias may in some way relate to the radiotherapy given to the patient.


Myeloma cells: surface morphology as seen by scanning and transmission electron microscopy. Cells from cultured murine myeloma cell lines and circulating leukemic plasma cells from two patients with generalized myeloma were studied by transmission and scanning electron microscopy. Both circulating and cultured cells exhibited consistent surface architectures. Microvilli and varying numbers of prominent blebs of different sizes were seen. The presence of surface blebs is a characteristic feature of secreting and nonsecreting myeloma cells.


Monoclonal gammopathy and subsequent multiple myeloma in a patient on chronic diphenylhydantoin therapy. The development of an IgG lambda-type monoclonal gammopathy and subsequent multiple myeloma in an epilepsy patient on diphenylhydantoin (DILANTIN) therapy for 20 years is reported. We regard the association recorded in this case to be a coincidence despite the known association between the drug and the development of immunosuppression and lymphoma. We recommended periodic examination of the serum proteins in patients receiving diphenylhydantoin in order to detect development of monoclonal gammopathy.


Rosette formation in chronic lymphocytic leukemia: studies of lymphocytes from peripheral blood and lymph node biopsy. Lymphocytes were obtained from a lymph node biopsy from a patient with chronic lymphocytic leukemia in whom B and T lymphocytes were present in equal percentages in the peripheral blood. The lymphocytes were examined for rosette formation with mouse and sheep erythrocytes in order to determine whether the leukemic process was of the B or T cell type.


Familial leukopenia among Yemenite Jews. Benign familial leukopenia was found in 75 of 200 healthy Yemenite Jews examined. The leukopenia was not a constant finding and was not associated with a tendency toward infection. HLA typing showed no significant differences in the frequency of the various HLA antigens between the subjects with and without leukopenia. No similarity was found between the HLA of the Yemenite Jews with leukopenia and that reported in black Africans with benign familial leukopenia. The suggestion of a genetic contribution from African blacks to Yemenite Jews is not supported by these results. The question remains to be answered whether the familial leukopenia in Yemenite Jews and black Africans is the result of a mutation.


Selective splenectomy in Hodgkin's disease, stages I and II. Results of treatment. Sixty-three patients with Hodgkin's disease, in stages I or II, asymptomatic (A) or symptomatic (B), were diagnosed and followed at the Chaim Sheba Medical Center from 1969 to 1976. Only 14 were staged pathologically. Until 1971, the patients received mantle or "inverted Y" therapy only; thereafter, an extended field that included mantle, upper abdomen and spleen irradiation was given. Symptomatic patients, as well as patients with extranodal involvement, received MOPP chemotherapy (nitrogen mustard, vincristine, procarbazine and prednisone) after termination of radiotherapy. Of 51 patients who were in stage IA or IIA, six relapsed 20 to 43 months after irradiation. Three had a pelvic recurrence; two of them were surgically staged. Thus, in only 1 of 51 patients could staging laparotomy possibly have detected pelvic disease and resulted in different therapy. Our results suggest that total nodal irradiation and staging laparotomy are not mandatory in stages IA and IIA of Hodgkin's disease. The group of 12 symptomatic patients is too small to allow us to draw definite conclusions as to the role of staging laparotomy and adjuvant chemotherapy. However, in view of the high relapse rate in the upstaged symptomatic patients, it seems that chemotherapy should be given to these patients.


Psoroptic ear mites in dairy goats.

Psoroptic ear mites in dairy goats. Of 24 adult dairy goats examined at necropsy, 21 were found to be infected with ear mites (Psoroptes cuniculi), but none had gross signs of ear scab. Clinical examination of approximately 200 live adult goats on 23 farms revealed ear scabs in only one animal; however, the frequency of head shaking and ear scratching was high. On one farm with 170 lactating does, most of 25 kids examined within 6 weeks of birth were found to be infested. Serial examination of growing kids on another farm revealed mites in the ears of kids by 10 days of age. The onset of clinical signs of ear mite infestation was evident in all kids on the property during the 3rd week of life. In one instance when infested adult goats and kids were penned with adult sheep and lambs, there was no evidence of cross infestation.


Capsulotomy technique in the presence of an anterior chamber lens. A modified Sato technique has proved to be a highly successful and atraumatic method of posterior capsulotomy in the presence of an anterior chamber lens. The lens remains undisturbed and iris-ciliary body, vitreous-retinal traction is avoided.


Prophylaxis of aphakic cystoid macular edema using topical indomethacin. The purpose of the present investigation was to define clinically the effect of topical indomethacin in preventing CME. The study was conducted on 50 patients who underwent bilateral intracapsular extraction of senile cataracts. One eye was used as the experimental subject and the other as the control. Postoperative alterations in the permeability of the blood-aqueous barrier and the chronological relationship of the changes in the retina and the blood-aqueous barrier were also studied. The mechanism underlying these postoperative ocular changes is discussed. In cases treated with indomethacin, the incidence and severity of CME were much milder than in the untreated fellow eye. These results were satistically significant. The chronological relationship between the hypothesized disruption of the blood-aqueous barrier and occurrence of CME after surgery strongly suggests that the latter occurs secondary to the former which, in turn, is initiated by prostaglandins synthesized in the iris during (and probably shortly after) the lens extraction. Thus prostaglandins may serve as a trigger in the production of the disorder, though this is not universally accepted.


Secondary lens implantation in aphakia: visual results and complications. We reviewed 70 cases that had undergone secondary lens implantation. The lenses used included 34 Medallion and 36 Choyce Mark VIII lenses. A 20/40 or better vision was present in 74.3% of the cases before implantation, and could be achieved postoperatively in 95.7% of the cases. Corneal changes, i.e. endothelial corneal dystrophy and induced astigmatism, were not noted in cases where Choyce Mark VIII lenses were used. Cystoid macular edema occurred in three cases where surgery followed an intracapsular cataract extraction (5.3%).


Visual results and complications of 500 intraocular lens implantations. These statistics reported for the visual results and complications of 500 intraocular lenses suggest that better visual results are obtained following extracapsular surgery. After all nonoperative causes for vision less than 6/12 were eliminated, 85.2% of the intracapsular cataract extractions had 6/12 or better vision. A similar group of planned extracapsular cataract extractions and phacoemulsifications yielded vision of 6/12 or better in 95% and 91.2% respectively.


The new soft intraocular lens implant.

The new soft intraocular lens implant. The 29 cases using the Type E soft implant demonstrated that: 1. This implant is acceptable to the eye. 2. Good visual acuity can be obtained from a soft implant. 3. Postoperative course is characterized by minimal reaction. 4. This intraocular implant design is acceptable to the eye and stable within it. As with any new procedure, the actual facts are only known after a number of years of experience. The potential long-term success of the soft implant opens up a new vista in the field of intraocular lens implantation. We hope that our continuing efforts will prove useful in approaching the goal of perfect sight following cataract surgery.


The posterior capsule and phacoemulsification. 1. The discission rate for 268 patients with intact posterior capsules with a 32-month follow-up in 43%. 2. The discission rate for 160 patients with intact posterior capsules and IOL implants with a 20-months follow-up in 20%. 3. To open or not open the posterior capsule at the time of surgery should be decided by the surgeons using these consistent statistics.


Clinical prediction versus ultrasound measurement of IOL power. 1. Clinical prediction was better than ultrasound prediction for the first 20 cases. It was approximately equal for the next 20 cases, but after this ultrasound was the more accurate. 2. There was no significant difference in ability of either clinical prediction of ultrasound to predict the power of various types of lenses, namely, 4-loop intracapsular lenses, 2-loop extracapsular lenses and Choyce-style anterior chamber lenses. 3. There was no clinically significant difference in accuracy of prediction regardless of the source (manufacturer) studied in this series. 4. Two major factors affecting results which ultrasound is totally helpless in predicting are surgically induced astigmatism and accuracy of stated lens power supplied.


Cataract wound closure with polyglactin 910 following insertion of a 4-loop Binkhorst lens: preliminary report. In this preliminary report our results with 8-0 braided polyglactin 910 suture for cataract wound closure after insertion of a 4-loop Binkhorst lens were encouraging. However, more experience is required before valid conclusions can be reached regarding its safety. Early experience indicates that the surgeon should approach the use of 9-0 monofilament polyglactin 910 suture for cataract wound closure following insertion of an intraocular lens with extreme caution.


Regulation of interstitial cell differentiation in Hydra attenuata. III. Effects of I-cell and nerve cell densities. The interstitial cell (i-cell) of hydra, a multipotent stem cell, produces two classes of differentiated cell types, nerve cells and nematocytes, throughout asexual growth. Using a new assay, the regulation of i-cell commitment to either nerve cell or nematocyte differentiation was investigated. This assay was used to determine the fractions of i-cells differentiating into nerve cells and nematocyte precursors in a variety of in vivo cellular milieus produced by hydroxyurea treatment, differential feeding, and reaggregation of dissociated cells. Nematocyte commitment was found to be positively correlated with the size of the i-cell population and independent of the axial position of the i-cells along the body column. This indicates that i-cell commitment to nematocyte differentiation may be regulated by feedback from the i-cell population. Nerve cell commitment was found to be correlated with regions of high nerve cell density. This suggests that nerve cell commitment is regulated by feedback from the nerve cell population or is dependent on axial position. Implications of such mechanisms for the regulation of i-cell population size and distribution are discussed.


Effect of temperature and divalent cations on the substratum attachment of rat hepatocytes in vitro. The attachment of rat hepatocytes to polystyrene-adsorbed serum protein is relatively insensitive to inhibitors such as dextran sulphate, cycloheximide, colchicine and cytochalasin B, and enzymes like trypsin and neuraminidase, but it is strongly dependent on divalent cations. Mg2+ supports attachment better than Ca2+, but a combination of both is required for maximal attachment. The attachment is very temperature-sensitive, with a biphasic Arrhenius plot indicating an activation energy of 123 kJ/mol above 34 degrees C and 374 kJ/mol below 34 degrees C. The adsorbed attachment-promoting serum factor is inactivated by trypsin, or by Ca2+-dependent proteases which contaminate commercial preparations of collagenase. The adsorbed factor is resistant to treatment with glutaraldehyde, neuraminidase and heating to 90 degrees C, whereas the same factor in the unadsorbed state (in serum) is destroyed by heating to 70 degrees C. The factor in serum is unable to compete with the adsorbed factor for cell binding, hence it would appear that adsorption to polystyrene induces the active, heat-resistant conformation of the factor.


Comparison of cell attachment and caseinolytic activities of five tumour cell types. We have examined the ability of 5 tumour cell types to attach to plastic flasks in medium containing either 10% foetal calf serum or 10% normal human serum and compared this ability with cell-associated caseinolytic activity. The cell types used included fibrosarcoma cells which were obtained from a methylcholanthrene-induced tumour in a C57 BL/6 mouse, the SV40-transformed 3T3 (BALB/c) cells, the Walker carcinosarcoma cells and 2 lines of HeLa cells. All 5 cell types attached to the flasks and spread out efficiently in medium containing 10% foetal calf serum. The walker carcinosarcoma cells and the 2 lines of HeLa cells also attached efficiently in medium containing 10% normal human serum and grew into monolayers in this medium. These 3 cell types had no detectable caseinolytic activity. The fibrosarcoma cells and the SV40-transformed 3T3 (BALB/c) cells did not attach in normal human serum-containing medium. These 2 cell types had readily detected caseinolytic activity. Normal human serum and foetal calf serum were compared for levels of protease-inhibitor activity. Human serum was found to have less activity than foetal calf serum against both trypsin and plasmin as well as the cell-associated caseinolytic activity. The low level of protease inhibitor activity in normal human serum may contribute to the inability of this serum to support the attachment of cells with detectable protease activity because the addition of protease inhibitors such as soybean trypsin inhibitor, lima bean trypsin inhibitor and bovine pancreas trypsin inhibitor to normal human serum dramatically enhanced cell attachment. In contrast to this, the addition of E-amino-n-caproic acid to normal human serum and the removal of plasminogen from normal human serum did not enhance its capacity to support cell attachment.