Lesson Overview Lesson Overview Human Chromosomes Lesson Overview 14.1 Human Chromosomes.
CHROMOSOMES IN HUMAN RABIES
1
102 The foregoing reasoning might explain the eventual occurrence of post-propranolol hypoglycsemia in a healthy person or in a maturity-onset diabetic receiving hypoglycsmic agents. Since sulphonylurea compounds suppress hepatic glucose pro- duction,l" this effect might be of significance in combination with the actions of propranolol. But the p-receptor effect on glucose homcrostasis is likely to be weaker than cf-adrenergic action, since, with adrenaline and noradrenaline stimulation, in healthy subjects, the net response is characteristic of a-adrenergic stimulation-i.e., hyperglycemia and suppression of insulin secretion 3; and in man, after propranolol, &bgr;-adren- ergic blockade is expected to cause relative dominance of a-actions. Propranolol did not appreciably or consistently influence F.F.A. levels at rest, and during starvation for more than 56 hours. As concluded earlier 16 adrenergic mechanisms play little part in basal and starvation-stimulated fat mobilisation. Nicotinic acid has been variously reported as both increasing and impairing glucose tolerance." We have shown that it has a biphasic effect," which is not influenced by propranolol. There is some similarity between the metabolic actions of nicotinic acid and phenoxybenzamine, including the intensify- ing influence of starvation. Finally, attention is drawn to the absence of interdependence between the changes of B.G. and F.F.A. concentrations in the diverse metabolic situations provoked by autonomic blockade and nicotinic acid. On the other hand, it seems that the more pronounced increases of B.G. and F.F.A. levels after both propranolol and nicotinic acid during starvation might be related to a common factor-i.e., the diminished insulin secretion of prolonged fasting. E. J. PINTER C. J. PATTEE. Clinical Investigation Unit, Queen Mary Veterans Hospital, Department of Investigative Medicine, McGill University, Montreal, Canada. G. PETERFY J. M. CLEGHORN. Allan Memorial Institute, Royal Victoria Hospital, Montreal, Canada. CHROMOSOMES IN HUMAN RABIES SIR,-Chromosomal alterations have been described in the course of several viral diseases of man, such as chickenpox, measles, rubella, infectious hepatitis, infections mononucleosis, and mumps.18 11 Recently we have studied the peripheral-blood chromosomes of a patient with rabies. The patient was a 50-year-old man who had had his finger bitten by a young dog 2 months before admission. Unfortun- ately the dog had been killed in a small town and had not been studied. The patient had not had antirabic vaccination. A day before admission he developed a temperature of 39.5°C (103.1°F) and severe headache and dysphagia. He had areo- phobia and motor hyperexcitability, and any external stimulus caused laryngeal muscular contractions. There was sialorrhoea, and pronounced hydrophobia-this became worse, with laryn- geal spasms, when he tried to drink water. The patient died 2 days after admission. While the patient was in hospital peripheral-blood lympho- cytes were cultured by the technique of Moorhead et al.19 slightly modified. Well-spread metaphases were obtained after the 3rd day of culture, and 56 mitoses were thoroughly studied, with particular regard for chromosome breaks and other similar abnormalities that might indicate chromatid damage. A buccal smear was stained with thionin for sex-chromatin study. In 15. Ashmore, J., Cahill, G. F., Earle, A. S., Zotter, S. Diabetes, 1958, 7, 1. 16. Pinter, E. J., Pattee, C. J., Gold, A. The Endocrine Society Program of the Forty-Eight Meeting on Suppression of Fat Mobilisation, Chicago, Illinois, June, 1966. 17. Parsons, W. B., Jr. Archs intern. Med. 1961, 107, 653. Molnar, G. D. Metabolism, 1964. 13, 181. 18. Aula, P. Hereditas, 1963. 49, 451; E1-Alfi, O. S., Smith, P. M., Biesle, J. ibid 1965, 52, 285., Gripenberg, U. ibid. 1965, 54, 1; Harnden, D. G. Am. J. hum. Genet. 1965, 16, 204; Nichols, W. W., Levan, A., Hall, B., Osstergren, G. Hereditas, 1962, 48, 367. 19. Moorhead, P. S., Nowell, P. C., Mellman, W. J., Battips, D. M., Hungerford, D. A. Expl Cell Res. 1960. 20, 613. none of the 56 mitoses studied was there any break or abnormal chromosome. Modal chromosome number was 46 with XY sex-chromosome complement in 54 cells. 2 cells showed 45 chromosomes with evident loss of 1 each from group C and 1 group F respectively which were interpreted as technical arte- facts. The buccal smears were negative for sex chromatin. At necropsy multiple sections showed mild cerebral oedema with engorged capillaries in the white matter; and there was pulmonary congestion and oedema, haEmorrhagic tracheo- bronchitis, and bilateral bronchopneumonia. Microscopically, sections of Ammon’s horn cerebral cortex, and cerebellum, stained with haematoxylin and eosin, and Mallory’s aniline blue, showed typical Negri bodies within the cytoplasm of many neurons. There was in addition various degrees of neuronal degeneration, as well as lymphocytic cuffing of some capillaries. Cytoplasmic inclusions in the neurons, as evidenced by the presence of Negri bodies and the virus, pointed to primary cytoplasmic damage, probably at the level of the ribosomal system, by the virus of rabies.2O The absence of chromosomal abnormalities in peripheral- blood lymphocytes suggests that these cells, unlike those in other viral infections, are not affected during the stage of rabic encephalitis. Initial damage to the nuclei of nerve cells is not observed in human cases of rabies in contrast to what is seen in other viral encephalites, such as herpes simplex. In the present study, however, the possibility of selective damage of the chromatin in neurons and glial cells cannot be ruled out. HÉCTOR MÁRQUEZ-MONTER FRANCISCO J. HIGUERA-BALLESTEROS SUSANA ALFARO-KOFMAN ESTEBAN GARCÍA MONTE MAYOR. Pathology Unit and Infectious Diseases Section, Secretariat of Public Health, Mexico. AMADOR GONZÁLEZ-ANGULO. Investigations Department, National Medical Center Mexican Institute of Social Security, Mexico City. EXTRA MINUTE CHROMOSOME IN CYCLOPS SIR,-In contradiction to an earlier observation 21 I have found 47 chromosomes in 17 (30%) of 56 available mitoses in the second subculture of muscle fibroblasts from a live-born male cyclops. The extra chromosome was minute, and usually Extra minute chromosome of male cyclops with satellites (a) and adhering to the Y (b) or other chromosome (c). ( x 3000.) adhered to one of the other chromosomes (figure b and c), with small satellites seen in the rare cases when it was found separated (figure a). No other change ih chromosome structure was detectable in cells with either 47 or 46 chromosomes. The contrast with the large number of minute chromosomes found in tumour cytology, lymphoblasts,22 or in the case of Ellis et al. 23 is because the satellites mostly cause entanglement 20. Andrewes, C. Viruses of Vertebrates; p. 152, London, 1964; Matsumoto, S. Virology, 1962, 17, 198; Miramoto, K., Matsumoto, S. J. Cell Biol. 1965, 27, 677. 21. Sohval, A. R. Am. J. Med. 1961, 31, 397. 22. McCarthy, R. E., Junius, V., Farbers, S., Lazarus, H., Fooley, G. E. Expl. Cell Res. 1965, 40, 197. 23. Ellis, I. R., Marshall, R., Penrose, L. S. Ann. hum. Genet. 1962, 26, 77.
Transcript of CHROMOSOMES IN HUMAN RABIES
102
The foregoing reasoning might explain the eventual occurrenceof post-propranolol hypoglycsemia in a healthy person or in amaturity-onset diabetic receiving hypoglycsmic agents. Sincesulphonylurea compounds suppress hepatic glucose pro-duction,l" this effect might be of significance in combinationwith the actions of propranolol. But the p-receptor effect onglucose homcrostasis is likely to be weaker than cf-adrenergicaction, since, with adrenaline and noradrenaline stimulation,in healthy subjects, the net response is characteristic of
a-adrenergic stimulation-i.e., hyperglycemia and suppressionof insulin secretion 3; and in man, after propranolol, &bgr;-adren-ergic blockade is expected to cause relative dominance ofa-actions. Propranolol did not appreciably or consistentlyinfluence F.F.A. levels at rest, and during starvation for morethan 56 hours. As concluded earlier 16 adrenergic mechanismsplay little part in basal and starvation-stimulated fatmobilisation.
Nicotinic acid has been variously reported as both increasingand impairing glucose tolerance." We have shown that it hasa biphasic effect," which is not influenced by propranolol.There is some similarity between the metabolic actions ofnicotinic acid and phenoxybenzamine, including the intensify-ing influence of starvation.
Finally, attention is drawn to the absence of interdependencebetween the changes of B.G. and F.F.A. concentrations in thediverse metabolic situations provoked by autonomic blockadeand nicotinic acid. On the other hand, it seems that the morepronounced increases of B.G. and F.F.A. levels after both
propranolol and nicotinic acid during starvation might berelated to a common factor-i.e., the diminished insulinsecretion of prolonged fasting.
E. J. PINTERC. J. PATTEE.
Clinical Investigation Unit,Queen Mary Veterans Hospital,
Department of Investigative Medicine,McGill University, Montreal, Canada.
G. PETERFYJ. M. CLEGHORN.
Allan Memorial Institute,Royal Victoria Hospital,
Montreal, Canada.
CHROMOSOMES IN HUMAN RABIES
SIR,-Chromosomal alterations have been described in thecourse of several viral diseases of man, such as chickenpox,measles, rubella, infectious hepatitis, infections mononucleosis,and mumps.18 11 Recently we have studied the peripheral-bloodchromosomes of a patient with rabies.The patient was a 50-year-old man who had had his finger
bitten by a young dog 2 months before admission. Unfortun-
ately the dog had been killed in a small town and had not beenstudied. The patient had not had antirabic vaccination. A daybefore admission he developed a temperature of 39.5°C
(103.1°F) and severe headache and dysphagia. He had areo-phobia and motor hyperexcitability, and any external stimuluscaused laryngeal muscular contractions. There was sialorrhoea,and pronounced hydrophobia-this became worse, with laryn-geal spasms, when he tried to drink water. The patient died2 days after admission.
While the patient was in hospital peripheral-blood lympho-cytes were cultured by the technique of Moorhead et al.19slightly modified. Well-spread metaphases were obtained afterthe 3rd day of culture, and 56 mitoses were thoroughly studied,with particular regard for chromosome breaks and other similarabnormalities that might indicate chromatid damage. A buccalsmear was stained with thionin for sex-chromatin study. In
15. Ashmore, J., Cahill, G. F., Earle, A. S., Zotter, S. Diabetes, 1958, 7, 1.16. Pinter, E. J., Pattee, C. J., Gold, A. The Endocrine Society Program of
the Forty-Eight Meeting on Suppression of Fat Mobilisation, Chicago,Illinois, June, 1966.
17. Parsons, W. B., Jr. Archs intern. Med. 1961, 107, 653. Molnar, G. D.Metabolism, 1964. 13, 181.
18. Aula, P. Hereditas, 1963. 49, 451; E1-Alfi, O. S., Smith, P. M., Biesle, J.ibid 1965, 52, 285., Gripenberg, U. ibid. 1965, 54, 1; Harnden, D. G.Am. J. hum. Genet. 1965, 16, 204; Nichols, W. W., Levan, A., Hall, B.,Osstergren, G. Hereditas, 1962, 48, 367.
19. Moorhead, P. S., Nowell, P. C., Mellman, W. J., Battips, D. M.,Hungerford, D. A. Expl Cell Res. 1960. 20, 613.
none of the 56 mitoses studied was there any break or abnormalchromosome. Modal chromosome number was 46 with XYsex-chromosome complement in 54 cells. 2 cells showed 45chromosomes with evident loss of 1 each from group C and 1
group F respectively which were interpreted as technical arte-facts. The buccal smears were negative for sex chromatin.At necropsy multiple sections showed mild cerebral oedema
with engorged capillaries in the white matter; and there waspulmonary congestion and oedema, haEmorrhagic tracheo-
bronchitis, and bilateral bronchopneumonia. Microscopically,sections of Ammon’s horn cerebral cortex, and cerebellum,stained with haematoxylin and eosin, and Mallory’s anilineblue, showed typical Negri bodies within the cytoplasm ofmany neurons. There was in addition various degrees ofneuronal degeneration, as well as lymphocytic cuffing of somecapillaries. Cytoplasmic inclusions in the neurons, as evidencedby the presence of Negri bodies and the virus, pointed toprimary cytoplasmic damage, probably at the level of theribosomal system, by the virus of rabies.2OThe absence of chromosomal abnormalities in peripheral-
blood lymphocytes suggests that these cells, unlike those inother viral infections, are not affected during the stage of rabicencephalitis. Initial damage to the nuclei of nerve cells is notobserved in human cases of rabies in contrast to what is seenin other viral encephalites, such as herpes simplex. In the
present study, however, the possibility of selective damage ofthe chromatin in neurons and glial cells cannot be ruled out.
HÉCTOR MÁRQUEZ-MONTERFRANCISCO J. HIGUERA-BALLESTEROSSUSANA ALFARO-KOFMANESTEBAN GARCÍA MONTE MAYOR.
Pathology Unit andInfectious Diseases Section,Secretariat of Public Health,
Mexico.
AMADOR GONZÁLEZ-ANGULO.
Investigations Department,National Medical Center
Mexican Instituteof Social Security,
Mexico City.
EXTRA MINUTE CHROMOSOME IN CYCLOPS
SIR,-In contradiction to an earlier observation 21 I havefound 47 chromosomes in 17 (30%) of 56 available mitoses inthe second subculture of muscle fibroblasts from a live-bornmale cyclops. The extra chromosome was minute, and usually
Extra minute chromosome of male cyclops with satellites (a) andadhering to the Y (b) or other chromosome (c). ( x 3000.)
adhered to one of the other chromosomes (figure b and c), withsmall satellites seen in the rare cases when it was found
separated (figure a). No other change ih chromosome structurewas detectable in cells with either 47 or 46 chromosomes.The contrast with the large number of minute chromosomes
found in tumour cytology, lymphoblasts,22 or in the case ofEllis et al. 23 is because the satellites mostly cause entanglement20. Andrewes, C. Viruses of Vertebrates; p. 152, London, 1964; Matsumoto,
S. Virology, 1962, 17, 198; Miramoto, K., Matsumoto, S. J. Cell Biol.1965, 27, 677.
21. Sohval, A. R. Am. J. Med. 1961, 31, 397.22. McCarthy, R. E., Junius, V., Farbers, S., Lazarus, H., Fooley, G. E.
Expl. Cell Res. 1965, 40, 197.23. Ellis, I. R., Marshall, R., Penrose, L. S. Ann. hum. Genet. 1962, 26, 77.
