PROCEEDINGS OF THE LATVIAN ACADEMY OF SCIENCES

SECTION B: NATURAL, EXACT AND APPLIED SCIENCES
(ISSN 1407-009X, Language: English)

Volume 56 (2002) Number 1/2

ENDOPOLYPLOIDY IN DEVELOPMENT AND CANCER: A POSSIBLE RELATION TO THE GENOTOXIC RESISTANCE OF MALIGNANT TUMOURS

Jekaterina Ērenpreisa and Andrejs Ivanovs
Biomedicinal Research and Studies Centre, University of Latvia, Rātsupītes ielā 1, Rīgā LV-1067 LATVIA; E-mail: katrina@biomed.lu.lv
Proc. Latvian. Acad. Sci., Section B, Vol. 56 (2002), No. 1/2, pp. 1–6 [Review].

Endopolyploidy (multigenomic cells) is ancient in evolution, and it occurs in the life- and cell-cycles of primitive forms. It is wide-spread in ontogenesis of protists, insects, and plants, and also to a certain extent in mammals. Endocycles are observed in the far-progressed tumours of various organs, and they are induced in resistant tumours in response to genotoxic damage. Through the induced endopolyploidy stage, these tumour cells survive and return to diploidy and mitosis. Evidence from various sources suggests the occurrence of shifts between the mitotic cycle and the endocycle in malignant tumours lacking function of the ‘genome guardian’ p53 tumour suppressor gene. We hypothesise that transient endopolyploidy, by-passing mitotic arrest in cells with damaged DNA, and providing them with a survival advantage due to evolutionary conservative DNA repair programmes, may contribute to the mechanisms of genotoxic resistance of tumours.

Key words: endocycle, p53, tumour resistance, genotoxic damage.

PROTEASOMES IN PATHOLOGY

Nikolajs Sjakste, Tatjana Sjakste*, Ingrīda Rumba, and Uldis Vikmanis
Faculty of Medicine, University of Latvia, Šarlotes ielā 1a, Rīgā LV-1001, LATVIA; E-mail: sjakste@osi.lv
* Institute of Biology, University of Latvia, Miera ielā 3, Salaspils LV-2169, LATVIA
Proc. Latvian. Acad. Sci., Section B, Vol. 56 (2002), No. 1/2, pp. 7–16 [Review].

The review summarises information regarding the involvement of the proteasomes and other enzymes participating in ubiquitin-mediated proteolysis in pathological processes. The linkage of the proteasome gene polymorphism to several diseases is discussed. Mutations in genes encoding for ubiquitination- or deubiquitination enzymes cause Angelman’s, DiGeorge’s and velo-craniofacial syndromes, as well as juvenile Parkinson’s disease. Mutations in genes for proteins encoding for substrates of ubiquitin-proteasome pathways cause Liddl’s syndrome, Huntington’s chorea, late-onset Parkinson’s disease, Alzheimer’s disease, and cystic fibrosis. Polymorphism in LMP2 and LMP7 proteasomal core particle genes is linked to development and manifestations of insulin-dependent diabetes mellitus, juvenile rheumatoid arthritis ankylosing spondylitis, and some other autoimmune diseases. Muscle degradation in Duchenne muscular dystrophy and in distal myopathy with rimmed vacuoles largely occurs due to an increased proteasomal activity. As proteasome composition and proteasome activity are altered in neoplastic cells, novel antitumour drugs can be developed from the proteasome inhibitors.

Key words: proteasomes, cancer, diabetes, muscle dystrophy, autoimmune diseases, inherited syndromes.

ANTISENSE APPROACH OF INHIBITING REPLICATION OF HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE 1 (HTVL-1)

Karīna Ivanova and Modra Murovska
Augusts Kirhenšteins Institute of Microbiology and Virology, University of Latvia, Rātsupītes ielā 1, Rīgā LV-1067, LATVIA; E-mail: karina_ivanova@hotmail.com
Proc. Latvian. Acad. Sci., Section B, Vol. 56 (2002), No. 1/2, pp. 17–23 [Review].

Specific inactivation of gene expression is an attractive approach for development of successful antiviral therapy. Antisense nucleic acids have great promise in the treatment of retroviral infection. The potential application of the antisense approach for suppression of human retrovirus HTLV-1 is discussed. A brief overview of the biology and pathogenicity of HTLV-1, the antisense approach, the action of different classes of antisense compounds, and the delivery methods of antisense drugs into organisms, are provided. Also, the choice of the target gene for antisense inhibition of HTLV-1 and possible therapy strategies are discussed. In vitro studies of antisense nucleic acids effect on HTLV-1 replication are reviewed.

Key words: HTLV-1, antisense oligodeoxynucleotides, antisense RNA, ribozyme.

DOUBLE-STRANDED RNA INDUCED BY INTERFERON IN HUMAN CELL CULTURES CORRELATES WITH APOPTOSIS

Dace Pjanova, Rūta Brūvere, Ārija Volrāte*, Guna Feldmane*, Natālija Gabruševa, and Valts Loža
Biomedical Research and Study Centre, University of Latvia, Rātsupītes ielā 1, Rīga LV-1067, LATVIA; E-mail: dace@biomed.lu.lv
*Institute of Virology and Microbiology, Rātsupītes ielā 1, Rīga LV-1067, LATVIA
Proc. Latvian. Acad. Sci., Section B, Vol. 56 (2002), No. 1/2, pp. 24–29.

The study was part of a series of experiments carried out to test the proposal that the intracellular formation of double-stranded RNA (dsRNA) structures in cells is one of the cell responses to physiological stress. Homologous interferon (IFN) was used as a stress factor and the formation of dsRNA was studied in different human cell cultures incubated with IFN for 5-45 min, 6 or 24 h. The relationships between intracellular presence, the amount and localisation of IFN-induced dsRNA and the apoptosis were evaluated. The dsRNA was detected in situ by immunocytochemistry using monoclonal antibodies against the A-helix structure of natural dsRNA. We showed that exogenous IFN induces protein-non-linked dsRNA structures in the cell nuclei and nucleoli. In the cytoplasm, dsRNA appeared as a ribonucleoprotein complex which could be visualised only after pre-treatment of fixed cells with proteinase K. IFN-induced apoptosis occurred in association with the appearance of the induced dsRNA in the cytoplasm under conditions when the nuclear and nucleolar dsRNA’s were suppressed by actinomycin D.

Key words: interferon, double-stranded RNA, apoptosis, immunocytochemistry, cell cultures.

BRADYCARDIC REACTION TO CAROTID BARORECEPTOR ACTIVATION: EFFECT OF ORTHOSTASIS

Dace Klincāre and Andris Vītols
Latvian Institute of Cardiology, Pilsoņu ielā 13, Rīgā, LV 1002, LATVIA; E-mail: klints@latnet.lv
Proc. Latvian. Acad. Sci., Section B, Vol. 56 (2002), No. 1/2, pp. 30–35.

The aim of the study was to assess the effect of sympatho-vagal balance modifications caused by orthostasis on bradycardic reaction to carotid baroreceptor activation (?PI) in healthy subjects (HS) and in patients with essential hypertension (EH). ?PI was evaluated by neck suction method in supine position and after passive head-up tilt on 13 HS and 11 EH patients matched by age and gender. In supine position, mean arterial pressure (MAP) was increased (135 ± 17 vs. 101 ± 9 mm Hg) and the baseline pulse interval (PI; 885 ± 130 vs. 977 ± 116 ms) and ?PI (50 ± 31 vs. 76 ± 30 ms) were decreased significantly (P < 0.05) in EH patients, compared to HS. In upright position, ?PI decreased (to 28 ± 14 ms in EH and to 54 ± 21 ms in HS) along with baseline Pl reduction in both groups (to 780 ± 106 ms and to 729 ± 157 ms, respectively). A significant (P < 0.05) relationship was found between baseline PI and ?PI in the HS group (r = 0.57) as well as in the EH group (r = 0.84) in supine position. This relationship remained in upright position with r = 0.69 for both groups. Our studies indicate that sympathetic activation in upright position causes a decrease in baroreflex bradycardic reaction which is dependent on the baseline pulse interval, in both EH patients and healthy subjects.

Key words: sympatho-vagal balance, baroreceptor-cardiac reflex, orthostasis, essential hypertension.

SOFT TISSUE BALANCE IN HIP JOINT ARTHROPLASTY

Narunas Porvaneckas
Vilnius University, Faculty of Medicine, Šiltnamiu 29, LT-2043 Vilnius, LITHUANIA; E-mail: narunas.porvaneckas@mf.vu.lt
Proc. Latvian. Acad. Sci., Section B, Vol. 56 (2002), No. 1/2, pp. 36-41.

The aim of this work was to evaluate the outcome of hip joint replacement surgery applying soft tissue relaxation as well as hip rotation centre placement. Clinical experiments showed the efficiency of this procedure. The study cohort consisted of three patient groups: R group (n = 54), patients with a severe joint contracture; and C1 group (n = 55), patients with hip joint arthritis, having slight flexion and abduction contractures, and C2 group (n=53), patients with very severe flexion and abduction contractures as in R group. In R group patients, the replacement surgery was accompanied by an additional procedure of joint soft tissue relaxation. In both control groups-C1 and C2 groups-replacement surgery alone was applied. At the time of surgery, in all groups of patients, the acetabular components were placed approximately close to the anatomical rotation centre of the joint. The postoperative results showed that for patients of the R group in whom the range of motions had been very limited preoperatively, the soft tissue relaxation and restoration of the rotation centre resulted in significantly (P < 0.05) less damage to joints. We conclude that intraoperative soft tissue balance and implantation of the acetabulum close to anatomical rotation centre of the hip is the key for a good early functional follow-up results. The postoperative joint stability and mobility depend on the condition of the surrounding tissues and on the anatomically suitable position of the prosthesis components.

Key words: hip joint, replacement, soft tissue balance.

WOMEN’S REPRODUCTIVE TRACT INFECTIONS: INFLUENCE ON DURATION AND OUTCOME OF PREGNANCY

Dace Rezeberga, Gunta Lazdāne, Juta Kroiča*, Ludmila Sokolova**, and Uldis Teibe***
Department of Obstetrics and Gynecology, Medical Academy of Latvia, Dzirciema ielā 16, Rīga, LV-1007, LATVIA; E-mail: ginekol@latnet.lv
*Department of Microbiology, Medical Academy of Latvia, Dzirciema ielā 16, Rīga LV-1007, LATVIA
**Department of Pathology, Medical Academy of Latvia, Dzirciema ielā 16, Rīga LV-1007, LATVIA
***Department of Medical Physics, Medical Academy of Latvia, Dzirciema ielā 16, Rīga LV-1007, LATVIA
Proc. Latvian. Acad. Sci., Section B, Vol. 56 (2002), No. 1/2, pp. 42–47.

Since 1990, there has been an increase in the incidence of sexually transmitted infections (STI) in Latvia. Statistical data show STI as a significant cause of perinatal pathology. The following data were collected during antenatal screening in Latvia: incidence of STI and other microorganisms among pregnant women, risk groups for STI, associated social and environmental factors and the impact of microorganisms on pregnancy duration and outcome. The randomised study was begun in 1997 in five outpatient clinics in the capital city of Rīga. Till January 1, 2001, 345 pregnant women with antenatal care started in the 1st trimester had been included in the trial. Each completed a specially created questionnaire. On the 1st antenatal visit and after 35–37 weeks of gestation, the following infections were checked: hepatitis B, gonorrhea, syphilis, Trichomonas vaginalis, bacterial vaginosis (BV), Human Imunodeficiency Virus, Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, Gardnerella vaginalis, Streptococcus agalactiae (BGS), Staphylococcus aureus, Streptococcus group D, Candida, Human Herpes Virus 2, and Human Papilloma Virus. The following factors were compared: duration of pregnancy, labour/delivery and post-delivery period, health status and birth weight of neonate, and placental histological findings depending on the microorganisms found. The control group (n=123) consisted of pregnant women with none of the mentioned infections found. The incidence of STI in Latvia is low, 6%. Risk groups were: age <22 years (P < 0.01), more than four sexual partners during life time (P<0.05), low income (P < 0.01). A risk factor for BV was smoking (P < 0.01). Streptococcus D increased early miscarriage (P < 0.05). Ureaplasma and/or mycoplasma increased threatening miscarriage in the 1st and 2nd trimester (P < 0.05). Inflammatory changes in placenta were seen in the presence of Gardnerella vaginalis and BV (P < 0.05).

Key words: reproductive tract infections, risk factors, pregnancy duration, outcome of pregnancy.

HIGH IMPACT OF MALE INFERTILITY IN BARREN COUPLES IN LATVIA, 1998-2001

Juris Ērenpreiss, Solveiga Hlevicka*, and Rasa Rauda**
Family and Sexual Health Centre, Saharova ielā 16, Rīgā LV 1021, LATVIA; E-mail: family.center@latnet.lv
*State Family Health Centre, Grēcinieku ielā 34, Rīgā LV 1050, LATVIA
**Department of Medical Residency, Medical Academy of Latvia, Dzirciema ielā 16, Rīgā LV 1021, LATVIA
Proc. Latvian. Acad. Sci., Section B, Vol. 56 (2002), No. 1/2, pp. 48–51.

The aim of this study was to investigate the impact of the male factor in infertile couples in Latvia. We retrospectively analysed male reproductive health in 579 barren couples. In 78% of males, semen analyses were abnormal, according to standards of the World Health Organization. This proportion is much higher than the 50% usually reported in Europe. Retrospective analyses of both the medical history and the results of clinical examination were performed in search for reasons of this high proportion. Since the proportions of congenital abnormalities such as varicocele and cryptorchidism among the 579 men studied were rather low (18% and 2.1 %), but a considerable proportion (60%) had acquired pathologies (prostatitis and sexually transmitted diseases) currently or in history, and 43% of the men possessed leukocytospermia, we conclude that the high proportion of abnormal semen is due mostly to post-natally acquired factors, most probably of an infectious nature. The results of screening for other possible adverse factors with respect to male reproductive health are also shortly reported.

Key words: barren couples, male infertility, sexually transmitted infections, Latvia.

BIOMECHANICAL PROPERTIES OF THE OESOPHAGUS WALL UNDER LOADING IN ADULT HUMANS

Indulis Vanags, Aigars Pētersons, Iveta Ozolanta, Vladimirs Kasjanovs*, Jānis Laizāns*, Egils Vjaters, and Velta Ose**
Department of Anaesthesiology and Intensive Care, Medical Academy of Latvia, Dzirciema ielā 16, Rīgā LV-1007, LATVIA; E-mail: anestez@latnet.lv
*Department of Biomechanics, Rīga Technical University, Kaļķu ielā 1, Rīgā LV-1658, LATVIA
**Biomedical Studies and Research Centre, University of Latvia, Rātsupītes ielā 1, Rīgā LV-1067, LATVIA
Proc. Latvian. Acad. Sci., Section B, Vol. 56 (2002), No. 1/2, pp. 52–56.

The aim of this investigation was to study the strength and deformation properties of the human oesophagus wall in normal and pathological cases, in three anatomical parts of the organ, in persons ranging from the age of 19 to 89 years. The oesophagus wall displays anisotropy and non-uniformity of mechanical properties in longitudinal and circumferential directions. Higher resistance of the oesophageal wall occurs in the longitudinal direction. Longitudinally oriented collagenous fibres and their bundles determine the higher wall stiffness in this direction. Oesophagus stresses and strains are the greatest in the cervical part for all age groups. With age, the values of mechanical parameters of the oesophagus wall reduce, in particular beginning from 45 years, but the modulus of elasticity increases.

Key words: oesophagus strength, stress and strain, modulus of elasticity.

CHANNEL-FORMATION IN MUSCLE FIBRE MEMBRANE COMPARED TO ARTIFICIAL BILAYER MEMBRANES

Nora Švinka
Institute of Experimental and Clinical Medicine. O. Vācieša ielā 4, Rīgā LV-1004, LATVIA; E-mail: mbrazma@latnet.lv
Proc. Latvian. Acad. Sci., Section B, Vol. 56 (2002), No. 1/2, pp. 57–60.

The effects of the channel-formers (gramicidin A, head-to-head covalently linked gramicidin dimer, amphotericin B, amphotericin methyl ester, nystatin, mycoheptin, and levorin) on isolated skeletal muscle fibres of the frog were investigated and compared to the effects on similar characteristics of bilayers. There was a strong similarity between steady-state characteristics of antibiotic-induced conductance in muscle membrane and in bilayers: (i) blocking of gramicidin channels by TI⁺ ions; (ii) nearly second-order dependence of conductance on gramicidin concentration; (iii) selectivity-sequence of monovalent cations (NH₄ > Cs⁺ > Rb⁺ > K⁺ > Na⁺ > Li⁺). This suggests that the gramicidin channel induced in BLM may be used as a model of the gramicidin channel in biological membranes. In contrast, the kinetics of channel formation in biological and model membranes significantly differed. Therefore, no complete information about the kinetics of channel-formation and the reversibility of induced conductance in biological membranes can be deduced from the experiments with BLM.

Key words: gramicidin, polyene antibiotics, skeletal muscle fibre, cation conductance, channel-formation.

CADMIUM REDUCES THE HORMONAL SENSITIVITY OF FROG OOCYTES

Vija Vose, Henriks Zenkevičs, and Ausma Būcena
Institute of Biology, University of Latvia, Miera ielā 3, Salaspilī LV-2169, LATVIA
Proc. Latvian. Acad. Sci., Section B, Vol. 56 (2002), No. 1/2, pp. 61–63.

The effect of sturgeon Acipenser güldenstädti Br. gonadotropic hormone (GTH) on frog Rana temporaria L. oocyte maturation in vitro was investigated in relation to Cd²⁺ concentration. Cd ions were observed to bind with the test oocytes proportionally to the ion concentration in the test solution. The test oocytes had lower hormone sensitivity which was proportional to the increase of Cd ions bound to the oocytes.

Key words: cadmium ions, toxicity, frog oocytes, hormonal effects.

CONCENTRATIONS OF MERCURY (Hg) AND CADMIUM (Cd) IN THE BALTIC EELPOUT (Zoarces viviparus L.) FROM THE GULF OF RĪGA (LATVIA) AND THE ARCHIPELAGO SEA (SW FINLAND), INCLUDING A PARASITOLOGICAL REMARK

Heinz-Rudolf Voigt
Department of Limnology and Environmental Protection, P.O. Box 62, Infocenter FIN 00014, University of Helsinki-Helsingfors, FINLAND; E-mail: Heinz-Rudolf.Voigt@Helsinki.fi
Proc. Latvian. Acad. Sci., Section B, Vol. 56 (2002), No. 1/2, pp. 64–68.

Concentrations of mercury (Hg) and cadmium (Cd) were analysed from eelppout (Zoarces viviparus L.) caught in November 1997 from the Latvian coast off Roja in the Gulf of Rīga (Latvia) and at Brunskär off Nagu in the Archipelago Sea (SW Finland). In both muscle tissue and liver, the concentrations of Hg and Cd were higher in eelpout from the Archipelago Sea than in eelpout from the Gulf of Rīga. The concentrations of Hg were higher in muscle tissue than in liver; ratio 3:1 (Gulf of Rīga) and 2.6:1 (Archipelago Sea), but for Cd, the opposite was observed – 1:25 and 1:10, respectively. The food safety levels for Hg and Cd, in Latvia, Finland, and the European Union, were never exceeded. In the intestines of eelpout from the Gulf of Rīga, the eelpout nematode Hysteriothelacium aduncum (RUDOLPHI, 1802) was recorded at frequencies similar to those prior to the severe bacteriological vibrio-epidemics during the 1980s. Since the recovery in 1993–1994 of eelpout in SW Finnish coastal waters, this previously frequent parasite had been only occasionally observed.

Key words: mercury, cadmium, eelpout (Zoarces viviparus L.), eelpout nematode Hysteriothelacium aduncum (RUDOLPHI, 1802), Gulf of Rīga, Archipelago Sea, Baltic Sea.

LAKE-SHORE VEGETATION IN WESTERN LATVIA

Liene Salmiņa
Faculty of Biology, University of Latvia, Kronvalda bulv. 4, Rīgā, LV-1586, LATVIA; E-mail: Isalmina@com.latnet.lv
Proc. Latvian. Acad. Sci., Section B, Vol. 56 (2002), No. 1/2, pp. 69–77.

A study (field work was carried out in July 1999) of the vegetation of lakes in the western part of Latvia is presented. The data set includes 109 relevés from 6 lakes with a total of 102 species. Twelve plant communities belonging to the classes Phragmiti-Magnocaricetea and Scheuchzerio-Caricetea nigrae were distinguished. A new association for Latvia – Caricetum magellanicae – was described. The plant communities are floristically and ecologically characterised, and a synoptic table is given. Indirect gradient analysis was applied to detect the hypothetical underlying gradients. The main vegetation gradient was explained by transition from open water to mire and by pH. The physiognomy of vegetation changed along this gradient, and four vegetation types (open water, fringe, fen, and intermediate mire) were distinguished.

Key words: classification, lake terrestrialisation, ordination, plant communities.

MEMBERS OF THE LATVIAN ACADEMY OF SCIENCES ELECTED AT THE LAS GENERAL MEETING OF 29 NOVEMBER 2001

On 29 November 2001, the General Meeting of the Latvian Academy of Sciences elected altogether 19 members.

Eight members were elected to the LAS Division of Physical and Technical Sciences: Agris Gailītis (full member, physics), Juris Jansons (full member, mechanics), Andris Krūmiņš (full member, physics), Māris Ābele (corresponding member, astronomy), Leonīds Ribickis (corresponding member, power engineering), Jurijs Dehtjars (Yuri Dehtyar; corresponding member, physics), Oļģerts Dumbrājs (Olgierd Dumbrajs, foreign member, Finland; physics), Juris Pēteris Svenne (foreign member, Canada; physics).

Four members were elected to the LAS Division of Chemical, Biological, and Medical Sciences: Īzaks Rašals (Isaak Rashal; full member, biology), Arnis Vīksna (full member, medicine), Bruno Andersons (corresponding member, materials science), Ruta Muceniece (corresponding member, medicine).

Seven members were elected to the LAS Division of Social Sciences and the Humanities: Inesis Feldmanis (corresponding member, history), Benedikts Kalnačs (corresponding member, literary criticism), Aivars Tabuns (corresponding member, sociology), Dzintra Bonda (Zinny Bond, foreign member, USA; linguistics), Gunārs Asaris (honorary member, architecture), Maija Einfelde (honorary member, art), and Kārlis Zariņš (honorary member, art).

A HUMAN GENOME PROGRAMME FOR LATVIA’S POPULATION: ACCOUNT OF THE ANNUAL GENERAL MEETING OF THE LATVIAN ACADEMY OF SCIENCES HELD ON 23 MARCH 2001

Jānis Kristapsons and Alma Edžiņa
Proc. Latvian Acad. Sci., Section B, Vol. 56 (2002), No. 1/2, pp. 81–83.

Jānis Stradiņš, president of the LAS, opened the meeting with an address. Full Member of the LAS Elmārs Grēns, winner of the Prize of the Cabinet of Ministers in Science for 2000, delivered an academic lecture, “A Human Genome Programme – a Challenge of the 21st Century for the World and Latvia.” Latvia’s scientists have designed a long-term national project, “A genome database of Latvia’s population.” The main objective of the project is to collect a sufficient amount of genetic information of the Latvian population that will help to introduce the latest genetic discoveries sooner, as well as improve the health and life quality of the Latvian population and ensure the country a good starting position under the expected biotechnological revolution.

Speeches were delivered by Dr. habil biol. Astrīda Krūmiņa (on genomic studies and medicine), Dr. med. Romualds Ra?uks, member of the Saeima (Parliament of Latvia) (on legislation necessary for the implementation of the genome programme), Prime Minister Andris ??ēle (on competitiveness of the state, science, on the national budget). The General Meeting resolved to support the scientific motivation for the Genome Programme of the Latvian Population.

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