Document BRbvwrRyEyz4voJ6vLR7DLepk

Sc I e r>cc (i0)'. iq 70 k iMc 2. Comparison of M* mutant ami norpkrU derived from S636-1. Data on jr;m-s and spikes arc means as in Table 1. V vvleopiile length was obtained at 206C from ;; ' codlings from each of the measured Characteristic Mutant Normal (!.*>? leaf sheath (cm) Spike length (cm) Spikelets per spike (No.) ( vileoplilc length (cm) Seed weight (mg) 24.4 1.1.5* 21.5* 7.2* 29.5* 25.6 13.5 22,8 7.9 35.3 < Significant difference from normal (P < .05). 30-cm spacing in field plantings at Davis, California, iri 1968 and 1969, Prom 16 Mj* plants produced by 5636-1, live were classified as normal ar-d 11 as mutant type on the basis of ,;\>neaiance and culm measurements. The M* families from these plants were classified in the following year. All normal M# plants produced normal, nonsegregating families; 9 of 11 mutant plants produced both normal and mu tant plants in the M* families. The remaining two mutant M3 plants pro duced all mutant M4 progeny. Com plete dominance is indicated for this character because, based on measure ments of the culm, mutant Mg plants were phenotypically similar and pro geny-testing proved that some of the M;; plants were heterozygous. The data for M.t families fit a ratio of one mu tant to two segregating to one normal; in the segregating families, a ratio of three mutant to one normal was closely approximated. These results suggest that a single dominant gene conditions she mutant phenotype. Mutant plant >56364 produced all mutant M4 progenies, and S785-5 .segregated sim ilarly to S6364 in the M:i. Stability of expression of the mutant phenotype has been obtained through three gener ation?. This mutation mainly affects the 'k*n;ib of the first in ternode below the f(peduncle) (Table 1), and the deduction in length of lower internodes a: ;ic<! until there was no reduction > nUcrootles 5 and 6. In. litis regard it > dmilaf to mutants found by Konzak * at. ;6), The total height of the mu'!>v;, including the spike, is IS percent -s ih ..u ihnt of the normal phenotype. `v lent;.!i of the ling leaf sheath is not * -ucci.l i>, ihc mutant type (Table .2), hu igh elongation of the peduncle * .v l><; modified somewhat by popula- denary. This dutraclcmtic ap' T nfiy hns not been observed pre- will) wheat mut;tilts. It is the edified length of the Hag leaf )' R iv;o sheath that results m altered canopy structure of the population. At present it is not suggested that this is a desir able feature for improvement of photo synthetic efficiency, but it is believed that this mutant provides a means by which certain relationships of light in terception in the canopy may be evaluated. Translocation of carbohy drates from the flag leaf lamina and sheath or peduncle and lower internodes to the spike may be altered in this mutant and must be considered along with its effect on canopy struc ture. Whit respect to the subtended spike, mutant plants appear somewhat similar to the high-yielding TR-8' rice in which the panicle is displayed some what below the flag leaf lamina (7). Table 2 shows other effects appar ently associated with the mutant chat> acter: reduction in seed size, spike length, number of spikelets per spike, and coieoptile length. Coleoptile length has selective value for seedling emer gence, and the reduction in length with this mutant is less than with many short-statured wheats (8). Nilan (9) has pointed out that pleiotropism is a common feature of induced mutations in higher plants; he suggested that this is an indication of the "gross and extragenie nature of delectable mutations in plants." Detailed genetic and develop mental analyses are required to judge the appropriateness of this remark for the present mutant. The induction of dominant muta tions by chemical or physical means is quite rare (9); however, dominant short-stature mutations were found re cently in common wheat (10) and in durum wheat (II). With both of these mutants the normal relationship of flag leaf sheath and peduncle was main tained so that the presently described mutant is morphologically distinct, C, O. Qu a l s e t O. N. Fic k Department of Agronomy and Range Science, University of California, Davis 95616 M. J. Co n s t a n t in University of TennesseeAtomic Energy Commission, Agricultural Research Laboratory, Oak Ridge 37830 T. S. Os b o r n e Department of Biological Sciences, Smith College, Northampton, Massachusetts 01060 References and Notes 1. C. M. Donald, Euphytica 17, 385 (1968); -- in Proceedings of the Third Interna tional Wheat Genetics Symposium, K. W. Finlay and K, J. Sheppard, Eds. (Australian Academcy of Sciences, Canberra, 1968), p. 377; P. R. Jennings, Crop Set. 4, 13 (1964). 2. F. J, Grundbachcr, Hot. Rev, 29, 366 (1963). 3. C. O. Qualset, C. W. SchaUer, J. C. Wil liams, Crap Set. S, .489 (1965). 4. N. E. Borlaug. In Proceedings of the Third International Wheat .Genetics Symposium, K. W, Finlay and K. J. Sheppard, Eds. (Austra lian Academy of Sciences, Canberra, 1968). p. 1. 5. E. A. Jackson, Ayr. Sci. Pew 4 . 21 (1966), 6. C. F. Kcn/.nk, R, A. Nilan E, E. Froeso* Gcrtzcu, I. A. Ramirez, Ifcreditor Suppl. 2, 66 (1966). 7. International Rice Research Institute, Annual Report J966, M.uniu, P]ii:pph:cs. 8. R. E. Atlra,, O. A. Vogel. C. J. Peterson, Jr., Aston. J, 54, 347 (19621; J. T. Feather, C, O. Qualset, H. E. Vogt, Calif. Agr. 22(9), 12 (1968). 9. R. A. Nilan, Abh. Deal. Akad. Wiss. Berlin No. 2 (1967), p. 5. 10. S. C. Woo and C. F. Konzak, in The Nature, Induction and Utilization of Mutations in Plants (International Atomic Energy Agency, Vienna, in press). 11. A. Bozzini and G. T. Scarascia-Mugnozza, Wheat Inf. Serv. No. 23/24 (19671, p. 5. 12. Supported by AEC contract AT-40-1-GEN242, 25 February 1970; revised 12 June 1970 & if Demyelinatjttg EncejphalorayUopathy Associated with Lead Poisoning in Montanan Primates Abstract. Lead poisoning was diagnosed.in four primates by the finding of toxic amounts of had in tissues. Abnormalities in the bruin and spinal cord were characterized by vascular lesions and deinyelination. These findings suggest a new animal model for the study of demyelinaiion and strengthen the supposition that lead may be a factor in some idiopathic dcinyeliaaiing diseases. i' Reports of lead poisoning in nonhumim primates arc sparse. We are aware of only a few accidental poison ing (/), none cf which was necropsied, anu several experimental poisonings (2). This report sumnnm/os the findings in four primates in which accidental lead in tux real ion existed foi various lengths of time before death, A spectrum of central nervous system changes was found. The lesions closely resembled one or the other of two previously de scribed conditions of unknown cause in primates. A detailed study of a larger number of similar eases is being pre pared for publication elsewhere. i I: I i { N37526 1091 DUP050044090 Case l. A female Barbary ape (Macuvii sylvanus) was bom in an outdoor a 1 biseason cage where she resided for 22Vi months until found dead. Inter mittent convulsions had occurred over a period of 18 months. Gross necropsy findings were not remarkable and at tempts to isolate viruses from brain, cerebral spinal fluid, throat, and in testine were unsuccessful. Histologic examination revealed focal, symmetrical dcniyel I nation of subcortical wh ite matter (Fig, 1) .associated with degenera tive and pro!rfernlive vascular lesions (Fig. 2). Acid-fast intranuclear inclu sion bodies, typical of heavy metal poisoning, were found in hepatocytes and renal proximal tubular epithelial cells (Fig. 3). Wet liver and kidney tissue contained lead in concentrations of 110 and 120 parts per million, respectively. Case 2, An adult rcd-faccd macaque (Macaca speclosa) lived in an indoor cage for IIVz months prior to death. During the last 2 days of life he had a scries of convulsions. Gross necropsy findings were not remarkable, but histo logic examination of the brain revealed marked cortical edema, degenerative vasculitis,' and subcortical dcmvel illa tion. Acid-fast intranuclear inclusions were found in renal convoluted tubular epithelia and hepatocytes. Wet liver and kidney tissue contained 65 and 90 parts of lead per million, respectively. Case 3. A juvenile male red-faced macaque (Macaca speclosa) was ac quired and quarantined in a galvanized cage for 6 weeks before being placed in an indoor display cage. Eight weeks later he had a convulsion and was taken to the hospital where he appeared to be blind and had frequent intermittent con* Fig, 1. Focus of demyelination in subcortical white matter. Luxol blue stain. Fig. 2. Proliferative (upper left) and degenerative (lower right) vascular lesions in white matter. Hematoxylin and epsiri stain. Fig. 3. Acid-fast inclusion bodies (arrows) next to nucleoli of renal tubular epithelia. Ziehl-Neclscn acid-fast stain. Fig. 4. Marked cdenla and necrosis in cerebral cortex. Hematoxylin and eosin stain. Fig. 5. Severe demyelination in spinal cord. Luxol blue stain. 1092 vulsions for 6 days. The animal wv; comatose for most of the last 2 days oi hospitalization and euthanasia was per formed, At necropsy the cerebral cor tices were swollen, especially in the It ft occipital region, where the sulci were shallow and the gyri considerably i'Kuicned. Histologically there was marked diffuse cortical macrogliosis, edema, laminar necrosis (Fig. 4), proliferative vasculitis, and focal demyelination of the optic It acts. Acid-fast mtranude^ Inclusion bodies were prominent in both renal tubular epithelial cells and hepa tocytes. Analysis of\dehydrated, paraf fin-embedded liver tissue indicated 360 parts of lead per million. Case 4. An adult lesser spot-nosed guenon (Cercopithecus nictitam) sud denly became paraplegic. Since its ar rival in the collection 2 years before, it had been housed in an indoor cage during the winter and an adjoining out door cage during the summer. A pro lapsed intervertebral disk (T^-L*) was diagnosed and euthanasia was per* formed 2 weeks after the first clinical signs had been evidenced. The pro lapsed disk was confirmed at necropsy but no obvious compression of the spinal cord was found. The histologic lesions observed in the central nervous system were inconsistent with those as sociated solely with compression of the spinal cord. Severe, diffuse, nonmalacic demyelination extended throughout the length of the spinal cord (Fig. 5), and symmetrical, multifocal areas of demyeljnation were present throughout the subcortlciT white matter of the brain and optic tractg. Vascular lesions were sparse. Acid-fast intranuclear inclusion bodies were present in renal tubular epithelia and hepatocytes. Spectrographic analysis of wet liver indicated 10 parts of lead per million. Scrapings of paint from bars of both indoor and outdoor cages that housed the affected primates all contained load (some in excess of 5 percent)- Small chips of such paint ingested periodical ly could provide a toxic, and eventually, lethal dose. Chips of lead-containing paint are the most common source of lead poisoning in children (3) and dog* (4). In the first three primates, the clinical signs of lead encephalomyelopathy were primarily amaurosis and epilepsy* The lesions of the central nervous sys tem were characterized by proliferalive and degenerative vascular changes, edema, laminar necrosis, and demyclination. These signs and lesions were SCIENCE, VOL. K' DUP050044091 .strikingly similar tp those that have been described "for lead encephalopathy in children (5) and idiopathic amaurotic epilepsy of nonhuman primates (6-8), It is interesting to note that other work ers have suspected that a relationship may exist between lead poisoning and amaurotic epilepsy (8, 9) of monkeys. The last ease described differs from the others in that sudden paraplegia was present rather than epilepsy; vascular lesions were minimum, and ^bilateral svnimetrieal_jicmyelination was much more extensive. These signs and lesions ^criTessentialiy the same as those de scribed for idiopathic lcuko.encephalomyclosis of nonhuman primates, a dis ease that has occurred concurrently with amaurotic epilepsy (7). The lesions associated with lead poisoning in these four primates sug gest a new animal model for the study of demyelination and tend to support the"contentioiToF others that lead may iu some way be a factor in certain idio pathic demyelinating diseases of ani mals (9, 10) and man (11). R. M. Sa u e r National Zoological Park 11 'ashington, D, C, 20009 B. C, Zo o k Department of Pathology, School of Medicine, George Washington University, Washington, D.C. 20037 F, M. Ga r n e r Armed Forces Institute of Pathology, Washington, D.C. 20305 References and Notes 1. L. E, Fisher, /. Amer. Vet. Med, Ass. 12$, 478 (1954); D. tie Bisschop (Royal Society of Zoologists, d'Anvers), unpublished communi cation to Directors, International Union of Zoological Societies, Chicago (1956)> W. D. Uousei', J. Amer. Vet. Med, Ass., in press, 2. A. Ferraro and R. Hernandez, Psychiat. Quart. 6, 121 and 319 (1932); C. Lamport and J. E. Desmedt, C. R. Seances Soc. Blot. 160, 25.04 (19(56); Anonymous, Environ. Set. Tech. 2, 731 (1968), 3. H. Jncobziner, Clin. Pedlat, 5, 277 (1966). 4. B. C. Zook, J. L. Carpenter, E. B, Leeds, J. Amer. Vet, Med. Ass. 155, 1329 (1969). 5. A. Rentschcw, Acta Neuropathol 5, 133 (1965). 6. H. M. Lanrdon and W. B. Cadwallader, J. Comr. Pathol. 28, 334 (1915); H. Fox, in Diseases of Laboratory Primates, T. C, Ruch, Ed. (Saunders, Rhllatlclplila, 1959), p, 437; L. van Bopiocrt, Pull. Acad. Roy. Mdd. Betg. IS, 245 (1935); J. Bette Neurol. Psy chiat. 36, 1 (1936); ---- and H. J. Scherer, Z. Ges. Neurol. Psychiat. 152, 757 (1935); ---.--, Arch. Neurol. Psychiat. 40, 521 (1938). 7. 3. R. M, Junes and L. Z. Saunders, Compara, five Neuropathology (Academic Press, New York, 1962), pp. 67-76, 94-103, and 132, 8. J. F. Wright, Report on the National Zoo- logical Park, Smithsonian Report (U,S. Gov ernment Printing Office, Washington, D.C., I960), p. 164; ibid. (1961), p. 166; ibid. (1962), p. 169. 9. J. Minckler, Pathology of the Nervous Sys tern (McGraw-IIill, New York, 1968), pp. 65- 67. 10. J. R. M. Innes and G. D. Shearer, /. Comp. Pathol. Therap. 53, 1 (1940), 11. A. M. G. Campbell, G, Herdan, W. P. T. Tatlow, E. G. Whittle, Brain 73, 52 (1950); H. V. Warren, Nature 184, 56 (1959);-------- , R. E. Dclavault, C. H. Cross, Ann. N.Y. Acad. Sci. 136, 657 (1967); W. Cone, C. Russel, R. Harwood, Arch. Neurol. Psychiat. 31, 236 (1934); W, T. C. Verhaqirt, Amer. J. Dis. Child. 61. 1246 (1941); H. Eichhom, Med, Rlin. 9, 20.1 (19,13); Cl. cle Morsjer and Y. Chestii, Schweiz. Med. Wochschr, 82, 443 (1952); G. Hermann, Wien, Med. V/ochschr. 131, 65/ (1951); A. Berger, Psychicl. Neu rol. 25, 168 <1905). 22 June 1970 M Indole Metabolism in the Pineal Gland: A Circadian Rhythm in N-AcetyKransferase Abstract. The activity of N-acetyItransferase in the rat pineal gland is more dim 15 times higher at night titan during the day. This circadian rhythm persists in complete darkness, or in blinded animals, and is suppressed ia constant lighting, He N-acetyItransferase rhythm is 1800 out of phase with the serotonin rhythm <-nd is .similar to the norepinephrine and melatonin rhythms. Experiments in vitro 'hdicaie that norepinephrine, not serotonin, regulates the activity of N-acetyD ' onxjerase through a highly specific receptor. --Acetyltransferase converts seron:n to iV-accfylserotonin (!), In the 'oal gland, Y-acctylscrotonin is Oih-vlalcd by hydroxyindoIe-O-melhyl r: tVrase to form the pineal specific :)~j\ouncl melatonin (2). Our studies cultured rat pineal glands have h-'Aicd that TV-acetyltransferase ac' > is stimulated manyfold by the transmitter norepinephrine by ' of an adcnyl cyclase mechanism ` is dependent on protein sy.n- thesis (J). A-Acetyttransfcrase seems to regulate the synthesis of melatonin by limiting the availabiity of Y-acetyiserotonin for O-methylation (3), We now report that the activity of Y~ace(yl (ransferase in the rat pineal gland increases rapidly at night to val ues which are more than 15 times greater than the day values. This cir cadian rhythm (4) is 180 out of phase with the rhythm in pineal serotonin (5, 6) and is similar to the rhythm In the concentration of melatonin (7) and norepinephrine (8, 9) in the pineal, Male Osborne-Mendel rats (NIH strain) weighing 180 to 220 g were used. The intensity of light in cages was 108 to 340 lumen/m2. Animals were killed by a blow to the head, and within a minute the pineals were removed. Glands were stored for less than 5 minutes at room temperature in Ring er injection solution while the ex traneous tissue was removed. The activity of Y-acetyltransferase was de termined by a niodif<cation of a pre vious method (d). A single pineal gland was homogenized in 20 pi of QAM sodium phosphate buffer (pH 6.8) containing [14C]serotoriin (0.5 mM) and acetyl coenzyme A (0.5 mM). The reaction mixture was incu bated for 10 minutes at. 37C. The [^CJY-acetylserotonin and [14C]melatonin that were formed during incu bation were isolated by thin-layer chro matography and eluted, and the radioactivity was then determined. A circadian rhythm in the activity of Y-acetyltransferase is present in the rat pineal gland (Fig. 1). A 15-fold increase in enzyme activity occurs dur ing the first 3 hours of the dark period, suggesting that darkness may cue the rhythm. To determine whether this circadian rhythm could be endogenously gener ated in the absence of lighting shifts, we maintained some animals in con tinual darkness for 6 days. A com parison of the enzyme activity at 11:00 a.m. and 11:00 p.m. indicates that a rhythm does persist (Table 1), In the group tested at 11:00 a.m., the average of six of the seven enzyme activities was 45 units (a unit of activity is the number of picomeles of [^Cjserotpnin Y-acetylated per gland homogenate per hour). The remaining pineal had an activity of 720 units. A similar varia tion in the distribution of enzyme activ ities Was observed in the group tested at 11:00 p.m,, with the majority of the values greater than 800 units. The greatly increased variability In the data indicates that the pineal Y-acetyltransferase rhythm becomes asynchronous among a group of rats maintained in darkness. The exposure of rats to continual lighting suppresses the Y-acetyltnnsfera.se rhythm (Table I). Hie measure ment of Y-acctyltraoslerase at six evenly spaced times during a 24-hour period provided no evidence that a rhythm was present (JO), The sup- * HEMB-ER 1970 2093 I r! !; > T tJr n j: li :j .1 I i ! I .j1 I I' r i i it I || t i> ii i i DUP050044092