Hypothesis: A nicotine-dopamine interaction linking smoking with Parkinson's disease and tardive dyskinesia

1. Nicotine, an important pharmacological component of cigarette smoke, is known to have significant effects on central nervous system (CNS) dopaminergic function. Although acute doses of nicotine have been shown to facilitate dopamine release, recent data indicate that chronic nicotine treatment may actually decrease CNS dopamine turnover in the striatum. 2. A number of epidemiological investigations have demonstrated that individuals who are or who have been smokers are less likely to develop idiopathic Parkinson's disease (a disorder involving a deficit in nigrostriatal dopaminergic neurotransmission). In addition, there is preliminary evidence that individuals with tardive dyskinesia (a hyperkinetic movement disorder observed in some cases of chronic neuroleptic treatment and thought by some to be associated with striatal dopamine receptor supersensitivity) are more likely to be smokers. 3. A unitary hypothesis is presented, proposing that smoking in early adult life may decrease CNS catecholamine turnover, thereby protecting against free radical formation from catecholamine oxidation that in turn damages striatal neurons. These individuals are thereby "protected" from the later development of Parkinson's disease. In this hypothetical scheme, individuals who are given neuroleptics and who also are smokers may develop a greater degree of dopamine receptor supersensitivity due to combined receptor blockade by neuroleptics and a decrease in CNS dopamine turnover caused by nicotine, resulting in an increased prevalence of tardive dyskinesia in this group.     

Pericentric inversion of chromosome 19 in three families

Summary Pericentric inversion of chromosome 19 has been found in several members of three unrelated families from a restricted geographical region. In one of the families, an additional pericentric inversion of chromosome 9 was observed. Reproductive problems, multiple abortions in two families and a neonatal death in the third, were present. A review of previously described cases is included, and the genetic risk connected with this type of rearrangement is also discussed.     

Human sperm chromosome studies in a reciprocal translocation t(2;5)

Summary Sperm chromosome complements have been studied in a man heterozygous for a reciprocal translocation t(2;5)(p11;q15). Human sperm chromosomes were obtained after fertilization of zona-free hamster eggs. A total of 75 human sperm metaphases were analysed. Of the complements studied, 59 (78.6%) resulted from a 2:2 segregation and 16 (21.3%) from a 3:1 segregation, 4:0 segregation was not observed. Our results indicate that at least 36% of sperm complements were unbalanced with respect to the translocation. The frequency of other chromosome anomalies unrelated to the translocation was 16%.     

The altered expression of MHC-class II determinants on monocytes of cancer patients

Summary The expression of MHC class II determinants Ia.7 (detected by cross reactive mouse anti-Ia^k antibody) and HLA-DR on monocytes (MO) of gastric and colorectal cancer patients was examined. An increased proportion of MO bearing the Ia.7 determinant was found, while the number of MO expressing DR was not elevated. In gastric cancer patients the increased expression of the Ia.7 determinant was most pronounced in advanced cancer (stage IVA and IVB). The increased expression of this determinant was related to the presence of the tumour as the number of MO expressing Ia.7 decreased 6 months following surgical resection of the tumour. Further, the increased expression of Ia.7 on MO correlated with the tumour infiltration of the serosa. The Ia.7 determinants were mainly expressed on MO which also expressed the receptor for the Fc part of immunoglobulin. Immunostaining in cellular infiltrates surrounding the tumour revealed that Ia.7⁺ macrophages (MØ) were more numerous than in normal gastric mucosa and severe chronic gastritis and were mostly present in close proximity to tumour cells, while DR⁺ MØ were mainly localized within the stromal tissue of the tumour and their number was not increased in cancer infiltrates. These observations indicate that the Ia.7⁺ subpopulation of MØ may be involved in the anti-tumour response of the host.     

Revision of the Brazilian species of the genus Halipegus Looss, 1899 (Trematoda: Derogenidae)

Halipegus dubius Klein, 1905 is redescribed and illustrated from a Brazilian frog Leptodactylus ocellatus. The type-material of Halipegus genarchella (Travassos, Artigas & Pereira, 1928) and Halipegus parva (Travassos, Artigas & Pereira, 1928) are redescribed with original figures. New synonyms are proposed: Halipegus salmini Yamaguti, 1958 is considered a synonym of H. genarchella, H. tropicus (Manter, 1936) sensu Kloss (1966) of H. parva and Genarchella lenti Fábio, 1984 of H. overstreeti (Brooks, Mayes & Thorson, 1979) n. comb.     

Sequence of the human erythrocyte phosphoglycerate mutase by microsequencer and mass spectrometry

We have previously reported the isolation in pure form of the human erythrocyte phosphoglycerate mutase isozyme B. We now report the sequence of the whole protein and the identification of its N-terminal blocking group. The protein tryptic peptides of phosphoglycerate mutase isozyme B were isolated by high performance liquid chromatography and their sequence determined by microsequencing. The sequence and the nature of the blocking group of the N-terminal tryptic peptide was shown to be N-acetyl-Ala-Ala-Tyr-Lys by mass spectrometry. Overlaps of the tryptic peptides were obtained by studying the V8 Staphylococcus aureus protease peptides of the aminoethylated phosphoglycerate mutase isozyme B either by microsequencing or by mass spectrometry. The procedure used allowed us to obtain the sequence on a very small amount of material and in a short period of time. Our data agree well with those derived from the cDNA nucleotide sequence described by Sakoda et al. (Sakoda, S., Shanske, S., DiMauro, S., and Schon, E. A. (1988) J. Biol. Chem. 263, 16899-16905). In addition, our data directly indicate that the initiation codon does not introduce a methionine as N-terminal amino acid and allowed the identification of the acetyl N-terminal group.     

Nyctohemeral Rhythms of Gonadal, Thyroid and Pineal Function in the Hyperprolactinemic Male Rat

In young adult male rats bearing a donor anterior pituitary gland grafted for 3 weeks under a kidney capsule, serum prolactin (PRL) concentrations were elevated and exhibited a rhythm with the highest values in the light phase. Serum PRL in control animals did not exhibit a significant rhythm. Eutopic pituitary PRL content, manifesting a biphasic (12-hr) rhythm with crests during the day and night in controls, exhibited a similar pattern in grafted rats though an overall reduction in pituitary PRL content was seen in the grafted animals. Neither the normal biphasic serum testosterone rhythm nor the normal 24-hr rhythm (nocturnal surge) of pineal N-acetyltransferase activity and melatonin content were altered in the hyperprolactinemic rats. Serum thyroxine (T₄) and triiodothyronine (T₃) and their free indices (FT₄ I, FT₃ I) and serum thyrotropin (TSH) were highest during the day in controls and grafted rats and a 12-hr rhythmic component was detected in data for these variables. In the grafted animals, the 12-hr component was reflected in an additional peak at night detectable by testing of means. The overall serum T₄ FT₄ I, and TSH levels were lower in grafted rats though overall T₃ and FT₃I levels did not differ between grafted and controls. T₃ uptake (T₃ U) values were similar between controls and grafted rats, in both cases exhibiting a fall during the night. Changes in serum thyronines could not be explained by changes in serum binding as assessed by the T₃U₃ and thus may represent changes in thyroidal secretion of T₄. The rhythm in serum PRL of grafted rats suggests the presence of rhythmic circulating factor(s) capable of influencing ectopic lactotrophs. The reduced eutopic pituitary PRL content suggests a role for PRL in influencing eutopic lactotrophs in the pituitary-grafted hyperprolactinemic male rat model. Though circulating testosterone and pineal melatonin synthesis were not altered in this model, thyroid function appeared to be so.     

Tricyclic Imipramine Modification of the Circadian Rhythms of Hypothalamic Serotonin, its Precursors and Acid Catabolite in Individually Housed Rats

Circadian rhythms of serotonin (5HT), its precursors tryptophan (TP) and 5-hydroxy-tryptophan (5HTP) and its acid catabolite 5-hydroxy-indoleacetic acid (5HIAA), were determined in the hypothalamus of control rats and rats which had been treated continuously with subcutaneous imipramine (10 mg/kg/day) for 2 weeks.

Rats were individually housed and entrained to LD12:12. Controls showed the 5HT and TP peaks in the light and dark periods respectively, as reported in the literature, but no inverted correlation (antiphase) between SHT and 5HIAA rhythms.

Imipramine significantly modified circadian rhythm characteristics: the 5HT acrophase was advanced, that of TP and 5HIAA was delayed. Imipramine also significantly increased hypothalamic SHT and TP concentrations.     

The role of morphometry in the cytology of well-differentiated hepatocarcinoma and cirrhosis with atypia

A morphometric study was performed on 200 nuclei per case in six well-differentiated hepatocarcinomas and in six cirrhoses with cytologic atypia, using samples obtained by fine needle aspiration (FNA) biopsy of the liver. The parameters measured were the nuclear area, the nuclear perimeter and the maximum nuclear diameter. The nuclei of well-differentiated hepatocarcinomas could be distinguished from those of cirrhoses on the basis of the larger size and greater anisonucleosis of the former. A statistical analysis (using a two-sided t-test) of the means of the parameters showed significant differences between the two diagnostic groups. These results suggest that morphometric analysis can help in the differential diagnosis between well-differentiated hepatocellular carcinoma and cirrhosis with cytologic atypia in FNA biopsy samples.     

Selected chromosome counts of the Czechoslovak flora I

Chromosome numbers of the following nine taxa of the Czechoslovak flora are given:Atriplex rosea L.,Cardamine resedifolia L.,Groenlandia densa (L.)Fourr.,Isoëtes lacustris L.,Lysimachia nemorum L.,Parnassia palustris L.,Phelipanche caesia (Rchb.) Soják,Rumex patientia L. subsp.patientia andSymphytum officinale L. s. str. A new chromosome number of 2n=80 is reported forRumex patientia L. subsp.patientia. Chromosome numbers of another five taxa are first reported from Czechoslovakia. Each of the ascertained chromosome counts is discussed with respect to hitherto known reports.