Morphological variations of pigment granules in eyes of the rhesus monkey

Melanin granules of rhesus monkey eyes develop in four stages. Early in stage I, they are small, spherical or elongated, membrane-limited vesicles containing parallel arrays of membranes oriented along the long axis and having regular periodicity. Melanization of these membranes, which is indicated by increased thickness and electron opacity, leads to the formation of stages II and III granules. In stage IV, their internal structure is completely obliterated by electron-dense melanin. During this process of development, melanosomes are transformed from thin, long vesicles into large ovoid bodies. By 60 days of gestation, melanosomes have developed in the pigmented epithelium of the iris, ciliary body, and retina, those in the retina being more mature and fully pigmented than the others. Stromal pigment cells of the uveal tract develop later than those of the pigmented epithelium. Pigment first appears in the iris at 140 days, then in the ciliary body, and lastly (150 days) in the choroid, where only well-developed melanosomes are found. Melanosomes of the stromal pigment cells as well as those of the pigmented epithelium may have their origin in the iris. Early melanosomes (stage II) are present almost exclusively in the iridial cells whereas mature forms are found in the ciliary and retinal cells.     

Iris as a recipient tissue for pigment cells: Organized in vivo differentiation of melanocytes and pigmented epithelium derived from embryonic stem cells in vitro

Regenerative transplantation of embryonic stem (ES) cell-derived melanocytes into adult tissues, especially skin that includes hair follicles or the hair follicle itself, generally not possible, whereas that of ES cell-derived pigmented epithelium was reported previously. We investigated the in vivo differentiation of these two pigment cell types derived from ES cells after their transfer into the iris. Melanocytes derived from ES cells efficiently integrated into the iris and expanded to fill the stromal layer of the iris, like those prepared from neonatal skin. Transplanted pigmented epithelium from either ES cells or the neonatal eye was also found to be integrated into the iris. Both types of these regenerated pigment cells showed the correct morphology. Regenerated pigment epithelium expressed its functional marker. Functional blocking of signals required for melanocyte development abolished the differentiation of transplanted melanocytes. These results indicate successful in vivo regenerative transfer of pigment cells induced from ES cells in vitro. Developmental Dynamics 237:2394-2404, 2008. (c) 2008 Wiley-Liss, Inc.     

Blue nevus and melanosis of the prostate. Electron-microscopic and immunohistochemical studies

Two cases of blue nevus and one case of melanosis of the prostate were studied with ultrastructural and immunohistochemical methods. All patients complained of urinary obstruction, and the clinical impression in all was benign prostatic hyperplasia. Melanin was present in the stroma of the prostate in all cases. In one, pigment was also demonstrated both in benign and malignant epithelial cells. Electron microscopically, melanosomes in different stages were present in the two white patients, but only mature stage IV melanosomes were demonstrated in the black patient. The melanin in epithelial cells consisted only of mature melanosomes. Immunohistochemically, the stromal cells that contained melanin stained with S-100 protein. The evidence suggests that the pigmented cells in the prostatic stroma are melanocytes and the melanin in the glandular epithelium is a result of the transfer of pigment from the stromal melanocytes.     

成年大鼠眼睫状体缘色素上皮组织的神经前体细胞的培养和鉴定

目的　探讨成年大鼠眼睫状体缘色素上皮产生神经前体细胞的潜力及其生物学特征。方法　取成年SD大鼠睫状体缘处的色素上皮组织块 ,置于含bFGF和B2 7的DMEM/F12 无血清培养液中进行神经前体细胞培养 ,免疫组化反应染色鉴定细胞的表型。结果　培养 5～ 8d ,组织块长出由众多无色素和色素细胞构成的细胞集落 ,集落的大多数细胞处于增殖状态(BrdU反应阳性 ) ,并表达神经前体细胞的标志物 (nestin)。撤掉bFGF和B2 7,加入胎牛血清培养 3～ 5d ,集落的细胞发生分化 ,分别表达神经元和星形胶质细胞的标志物 (NSE、GFAP) ,但不表达少突胶质细胞的标志物 (O4 )。结论　由成年大鼠睫状体缘色素上皮长出的细胞集落不仅含有增殖能力和多分化潜能的神经前体细胞 ,而且尚含有色素细胞 ,该部位可能是视网膜神经感觉层和色素上皮共同保守的细胞生发带     

Localization of retinoid binding proteins, retinoid receptors, and retinaldehyde dehydrogenase in the chick eye

Retinoids have many functions in the eye, including, perhaps, the visual guidance of ocular growth. Therefore, we identified where retinoid receptors, binding proteins, and biosynthetic enzymes are located in the ocular tissues of the chick as a step toward discovering where retinoids are generated and where they act. Using antibodies to interphotoreceptor retinoid binding protein (IRBP), cellular retinol binding protein (CRBP), cellular retinoic acid binding protein (CRABP), cellular retinaldehyde binding protein (CRALBP), retinaldehyde dehydrogenase (RALDH), and retinoic acid receptors (RAR and RXR), we localized these proteins to cells in the retina, retinal pigmented epithelium, choroid and sclera of the chick eye. IRBP was detected in the photoreceptor layer and pigmented epithelium; CRBP was in the pigmented epithelium; CRABP was in amacrine and bipolar cells in the retina; CRALBP was in Müller cells, pigmented epithelium, choroid, and fibrous sclera; RALDH was in retinal amacrine cells, pigmented epithelium, and choroid; RAR was in amacrine cells, choroid, and chondrocytes and fibroblasts in the sclera; and RXR was in amacrine and ganglion cells, bipolar cell nuclei, choroid, and chondrocytes. We also found that the growth-modulating toxins colchicine and quisqualate destroyed selectively different subsets of CRABP-containing amacrine cells. We conclude that the distribution of proteins involved in retinoid metabolism is consistent with a role of retinoids not only in phototransduction, but also in maintenance of cellular phenotype and visual guidance of ocular growth.     

Swelling-activated chloride channels in aqueous humour formation: on the one side and the other

Aqueous humour is secreted by the ciliary epithelium comprising pigmented and non-pigmented cell layers facing the stroma and aqueous humour respectively. Net chloride secretion likely limits the rate of aqueous humour formation and proceeds in three steps: stromal chloride entry into pigmented cells, diffusion through gap junctions and final non-pigmented cell secretion. Swelling-activated chloride channels function on both epithelial surfaces. At the stromal surface, swelling- and cyclic adenosine monophosphate-activated maxi-chloride channels can recycle chloride, reducing net chloride secretion. At the aqueous-humour surface, swelling- and A3 adenosine receptor-activated chloride channels subserve chloride release into the aqueous humour. The similar macroscopic properties of the two non-pigmented cell chloride currents suggest that both flow through a common conduit. In addition, measurements of intraocular pressure (IOP) in living wild-type and mutant mice have confirmed that A3 adenosine receptor-activated agonists and antagonists increase and lower IOP respectively. Isolated ciliary epithelial cells are commonly perfused with hypotonic solution to probe and characterize chloride channels, but the physiological role of swelling-activated channels has been unclear without knowing their epithelial distribution. Recently, hypotonic challenge has been found to stimulate the chloride-sensitive short-circuit current across the intact bovine ciliary epithelium, suggesting that the net effect of the swelling-activated chloride currents is oriented to enhance aqueous humour formation. Taken together, the results suggest that swelling-activated chloride channels are predominantly oriented to enhance aqueous humour secretion, and these chloride channels at the aqueous surface may be identical with adenosine receptor-activated chloride channels which likely modulate aqueous inflow and IOP in the living mouse.     

Laminin production by human endometrial stromal cells relates to the cyclic and pathologic state of the endometrium.

The cyclic changes in the presence of the basement membrane glycoprotein laminin in endometrial stromal cells was studied by immunohistochemistry. The interstitial matrix around the stromal cells of the proliferative phase of the normal menstrual cycle was unreactive with antibodies to laminin. However, commencing with the secretory phase, stromal cells accumulated distinct cytoplasmic and pericellular laminin-immunoreactive material. The maximal amount of stromal cell-associated laminin was observed in predecidual cells of the late secretory phase. Thus, laminin immunostaining discriminates stromal cells of the proliferative phase (being "negative") from those in the secretory phase (being "positive"). Sixty-six cases of endometrial hyperplasia and adenocarcinomas were also stained with antibodies to laminin. Sixty-nine percent of biopsies of cystic hyperplasia and 30% of adenomatous hyperplasia contained laminin-positive stromal cells. Ultrastructural examination of stromal cells in cystic hyperplasia revealed the presence of pericellular basement membrane-like material, focally arranged into typical lamina rara and lamina densa. In contrast, stromal cells in the atypical adenomatous hyperplasia and adenocarcinomas did not react with antibody to laminin. The expression of laminin receptor in the stromal cells codistributed with laminin. Basement membranes of the surface epithelium, the glandular epithelium, and the vessels stained strongly with antibodies to laminin. In preneoplastic and neoplastic tissues, laminin immunostaining revealed discontinuous and defective basement membranes. In poorly differentiated carcinomas only sparse amounts of laminin-positive basement membrane were observed; these tumors, in contrast, exhibited cytoplasmic laminin and also significant immunoreaction with antibodies to laminin receptor.     

Ultrastructure of epithelial plaque formation and stromal cell transformation by post-ovulatory chorionic gonadotrophin treatment in the baboon (Papio anubis).

BACKGROUND: To understand factors controlling endometrial responses to pregnancy, we have established a model using the baboon and examined the effects of infused human chorionic gonadotrophin (HCG) on the preparation of the luminal epithelium and stromal cell differentiation for the establishment of pregnancy. METHODS: The ultrastructure of endometrium from normal day 10 post-ovulation animals, cycling females treated with either HCG or FSH (control), and a day 15 pregnant animal has been compared. RESULTS: In the control endometrium, the luminal epithelium was smooth and regular, with underlying spindle shaped stromal cells. In pregnancy, the luminal epithelium underwent a plaque reaction, while stromal cells enlarged and developed filament-rich cell processes. Infusion of HCG produced changes similar to those seen in pregnancy, with generalized plaque formation and stromal decidualization, while in the animal treated with FSH there was no response. CONCLUSIONS: This study indicates that infusion of HCG into the uterus can duplicate many of the responses of the endometrium to pregnancy, although in this case the plaque reaction involved the whole of the luminal epithelium, rather than only the implantation site as in pregnancy.     

Distinct subsets of stromal cells confined to unique microenvironments in human endometrium throughout the menstrual cycle.

Human endometrial stroma exhibits rather uniform morphology throughout the endometrium. However, predecidualization develops characteristically around vessels and subsequently around glands and under surface epithelium, demonstrating existence of regional differences among stromal cells. Immunoreactivity of stromal cells in endometrial tissues from various phases of the menstrual cycle, as elucidated by employing monoclonal antibodies to cytokeratin, vimentin, very late antigen-1 (VLA-1), Ber-EP4, and HLA-DR, revealed presence of phenotypically distinct subsets of stromal cells confined to unique microenvironments throughout the menstrual cycle. All stromal cells strongly expressed vimentin and weakly expressed cytokeratin. However, Ber-EP4 positive stromal cells were distinctly confined around glands and to the subluminal regions of the surface epithelium. The intervening stromal cells were Ber-EP4 negative. The HLA-DR positive stromal cells were characteristically present in three different locations: around glands and under surface epithelium, around blood vessels and around HLA-DR positive lymphoid cells. From all antigens studied, only expression of VLA-1 in the stromal cells showed a characteristic change throughout the menstrual cycle. Stromal cells in the proliferative and early secretory phases were VLA-1 negative. However, VLA-1 characteristically developed initially in the HLA-DR positive cells around vessels and then in HLA-DR/Ber-EP4 positive cells around glands and under surface epithelium. Eventually, all stromal cells in the upper functionalis expressed VLA-1 in the late secretory phase of the menstrual cycle. These data underscore a heterogeneity in stromal cells not exemplified by their morphology. Also, they provide a basis for understanding the differences that the stroma exhibits in morphologic and functional differentiation throughout the menstrual cycle.     

Phenotypic characterization of chicken bursal stromal elements

Many, if not all, of the different phases of intrabursal B-cell maturation are controlled by the stromal components. We have used an extensive panel of mAb to provide a detailed phenotypic profile of these cells. Antigenic specificities were defined for the entire surface epithelium, interfollicular surface epithelium, follicle-associated epithelium, basement membrane, basement membrane-associated epithelium. Several mAb were specific for the medulla, including those reactive with the stellate network of epithelial cells, isolated macrophages, and granular, apparently secreted antigens. One of these, MUI-92, appears to be bursa-specific. Two mAb reacted strongly with stellate cortical macrophages, one of which weakly stained similar cells in the medulla. MHC-class II antigens were expressed on endothelium of the corticomedullary junction, macrophagelike cells in the cortex, and medulla and B lymphocytes predominantly in the cortex. Collectively, these mAb have demonstrated the antigenically distinct nature of discrete regions in the bursa, but also the continuity of the surface epithelium with the corticomedullary junction and medulla. They represent excellent reagents for defining the stromal cell contribution of B-cell development.     

Identification of a unique epigenetic sub-microenvironment in prostate cancer

The glutathione S-transferase P1 (GSTP1) gene promoter is methylated in tumour cells in more than 90% of prostate carcinomas. Recently, GSTP1 promoter methylation was identified in tumour-associated stromal cells in addition to the tumour epithelium. To define the extent and location of stromal methylation, epigenetic mapping using pyrosequencing quantification of GSTP1 promoter methylation and an anatomical three-dimensional reconstruction of an entire human prostate specimen with cancer were performed. Normal epithelium and stroma, tumour epithelium, and tumour-associated stromal cells were laser capture-microdissected from multiple locations throughout the gland. As expected, the GSTP1 promoter in both normal epithelium and normal stromal cells distant from the tumour was not methylated and the tumour epithelium showed consistently high levels of promoter methylation throughout. However, tumour-associated stromal cells were found to be methylated only in a localized and distinct anatomical sub-field of the tumour, revealing the presence of an epigenetically unique microenvironment within the cancer. Morphologically, the sub-field consisted of typical, non-reactive stroma, representing a genomic alteration in cells that appeared otherwise histologically normal. Similar epigenetic anatomical mapping of a control prostate gland without cancer showed low background methylation levels in all cell types throughout the specimen. These data suggest that stromal cell methylation can occur in a distinct sub-region of prostate cancer and may have implications for understanding tumour biology and clinical intervention.     

Non-neuronal cells involved in the degeneration and regeneration of the fish retina

In the present work we show that during the degenerative process occurring after the cryo-elimination of the tench peripheral growing zone many non-neuronal cell types in addition to the resident microglial cells, appear within the affected areas. Some of them are normally found in the retina, such as the retinal pigmented epithelium cells and others originate from extra-retinal tissues. We identified these as granular leukocytes and macrophages. The microglial cells and macrophages, those resident in the sub-retinal space, and the invasive ones, act as phagocytes. The analysis of the injured retina following lesion shows that the invasive macrophages, arising from the scleral extra-retinal tissues, penetrate the neural retina, and migrate from the scleral to the vitreal portion. In contrast those coming from the vitreal extra-retinal tissues migrate in the opposite direction. Moreover, the retinal pigmented epithelium cells present remarkable modifications in their morphology and distribution and enter the neural retina, where they disrupt the surrounding tissue. We have also observed that this cryo-lesion causes an inflammation mediated by a type of granular leukocyte, denominated heterophils which penetrate the neural retina and probably come from the blood supply. Our results suggest that, during the first days after the lesion, the participation of diverse non-neuronal cells removing cell debris from the damaged zone should create a favourable environment allowing the regeneration of the neural retina.     

Ultrastructural observations on experimentally produced melanin pigmentation of the corneal epithelium.

Melanin pigmentation of the corneal epithelium was induced in pigmented guinea pigs by the topical application of colchicine to their eyes or by corneal cauterization with silver nitrate. With colchicine the pigmentation was preceded by the development of an abnormal corneal epithelium in which numerous cells became arrested in cell division. The corneal melanosis resulted largely from the migration of melanocytes into the corneal epithelium from the normally pigmented contiguous conjunctiva and to a lesser extent from the presence of melanin granules within corneal epithelial cells. In both models a leukocytic and vascular invasion of the cornea proceded and accompanied the migration of melanocytes into the corneal epithelium. Electron microscopy disclosed cells with the same morphology as conjunctival melanocytes between the epithelial cells of the cornea. Mature melanin granules were also present within some squamous epithelial cells as individual granules or as clusters. The ultrastructural findings are viewed in relation to how melanin granules are transferred from melanocytes to epithelial cells. Evidence is presented which suggests that malanin granule transfer may follow the fusion of the membranes of the melanocytes and epithelial cells.     

Quantitative studies of the effect of progesterone on endometrial morphology of the spayed rat.

The effects of various dosages and of various time periods of treatment with progesterone have been studied in the spayed, mature rat. Test objects were the cells of the luminal epithelium and of the endometrial stroma which were examined by qualitative and quantitative electron microscopy. No significant response was observed in epithelial or stromal cells until after 12 hrs of progesterone treatment. The nuclei of both cell types were then more circular than earlier with reduced long diameters. The functional significance of this change in configuration is unclear since only in the stromal cells was it followed by nuclear growth. Further, after 12 hrs of treatment the relative amounts of mitochondria and granular endoplasmic reticulum of stromal cells were reduced while the volume of the stromal cell cytoplasm appeared enlarged. This is taken as evidence that progesterone causes an intracellular oedema probably by decreasing cell membrane permeability. This response is probably not specific for the stroma but also includes the luminal epithelium, although the volume of the epithelial cell cytoplasm could not be determined here. Nucleolar enlargement did occur in stromal cells and was observed after 12 hrs of treatment but was not significant until after 24 hrs. At this point of time the net amount of granular endoplasmic reticulum in stromal and epithelial cells was increased indicating an increased protein synthesis in both cell types. However, only in the stromal cells was this associated with nucleolar enlargement, which supports the idea that progesterone stimulates protein synthesis through different mechanisms in the two cell types. Testing various dosages of progesterone showed that 0.5 mg had an effect similar to 5 mg of progesterone. When 0.05 mg progesterone was injected the only effect observed was an increase in the amount of apical vesicles of the luminal epithelium, showing that the epithelium is more sensitive to progesterone than the stroma.     

Pigmented squamous intraepithelial neoplasia of the esophagus

Squamous cell carcinoma (SCC) usually lacks melanocytes within the tumor. A few reports have documented invasive SCC or SCC in situ (intraepithelial neoplasia, IEN) with melanocytic hyperplasia within the tumor, referred to as pigmented SCC, in some organs. However, case series of pigmented SCC or IEN of the esophagus have not yet been reported. This is the first study to analyze the incidence and clinicopathological features of pigmented SCC or IEN of the esophagus. We reviewed 18 surgically-resected and 122 endoscopically-resected esophageal specimens, including 79 cases of IEN. Three cases of pigmented IEN were observed in this series, and all of them were located in the middle to lower third of the esophagus. Two of 3 cases had melanocytosis in the non-neoplastic squamous epithelium around the IEN. The incidence of pigmented IEN was 2.5% of all endoscopically resected specimens and 3.8% of IEN cases. No pigmented invasive SCC was detected in both endoscopically-resected and surgically-resected specimens. The mechanism of pigmentation of esophageal IEN is unknown. However, production of melanocyte chemotactic factors by tumor cells has been demonstrated in pigmented SCC of the oral mucosa. Moreover, two of 3 cases of pigmented IEN in the present series had melanocytosis in the non-neoplastic squamous epithelium, and melanocytosis is thought to be associated with chronic esophagitis, therefore, it has been hypothesized that various stimuli can cause pigmentation in squamous epithelium. Additional studies are needed to clarify the mechanism of pigmentation in squamous IEN of the esophagus.     

Ultrastructure of the gut caecal epithelium of Pricea multae (Monogenea: Polyopisthocotylea)

 Ultrastructural observations of the gut caecal epithelium of Pricea multae revealed the presence of pigmented and non-pigmented digestive cells. The pigmented digestive cells were separated by a connecting syncytium and appeared elongated,with numerous vesicles appearing toward the apical cell surface. They were characterised by granular inclusions in the form of electron-dense pigments, which were eliminated by exocytosis. These cells and their lamellar connecting syncytium were observed projecting into the gut lumen. Transverse sections of the gut epithelium revealed intact portions of digestive cells lying in the lumen. Endocytosis at the apical surface of the pigmented digestive cells gave rise to the formation of granular inclusions, which appeared as electron-dense pigments confined to lysosomal vesicles within the digestive system. Electron X-ray microanalysis indicated these granules were primarily composed of iron, demonstrating that P. multae is a blood-feeder. The connecting syncytium, while probably involved in a structural, supportive role, may additionally function in the absorption of micromolecular nutrients from the host blood meal. Received: 20 June 1995 / Accepted: 3 November 1995     

Changes in cellular dynamics during the development of the ciliary epithelium.

Eye growth and the formation of the ciliary folds during development depend on the maintenance of normal intraocular pressure. In this study we measured labeling index, packing density, height, and volume of the prospective ciliary epithelial cells during the early development of the eye in chicken embryos. Changes in these values were related to the formation of the ciliary folds and to experimental alterations of intraocular pressure. These variables changed independently in the outer, pigmented layer and the inner, non-pigmented epithelial layer of the ciliary epithelium. The labeling index in the pigmented epithelium declined steadily throughout development. Decreases in cell density and increases in cell height resulted in a four-fold increase in calculated average cell volume in the pigmented epithelium during Hamburger-Hamilton stages 29 and 30, the day before the formation of the ciliary folds. In the non-pigmented epithelium, the labeling index increased abruptly at stage 31, the stage at which ciliary folds begin to form. At the same time there was a three-fold increase in average cell volume. When intraocular pressure was reduced by intubating the eye, the formation of ciliary folds was prevented. Intubation also blocked the increase in labeling index and blunted the increase in cell volume that normally occur in the non-pigmented epithelium at the time of fold formation. In the pigmented epithelium, intubation caused a sustained, three- to six-fold increase in cell volume, but had no effect on labeling index. Based on these data, we suggest that increases in cell number and volume just before and during the formation of ciliary folds contribute to the formation of the ciliary folds.     

Müllerian adenosarcoma of the uterine cervix

We present a tumor of the uterine cervix that was composed of histologically benign glandular epithelium and a malignant stromal component, justifying the term müllerian adenosarcoma. Ultrastructurally the stromal cells resemble the endometrial stromal cells, the tumor cells of an endolymphatic stromal myosis of the uterine cervix, and the stromal cells of a stromomyoma of the uterus. In addition there is evidence strongly suggesting a differentiation toward smooth muscle. The patient exhibited no evidence of disease one year after surgery.     

Stromal expression of vascular endothelial growth factor correlates with tumor grade and microvessel density in mammary phyllodes tumors: a multicenter study of 185 cases

A retrospective review of 185 mammary phyllodes tumors (105 benign, 51 borderline, 29 malignant) from 4 centers was performed by immunohistochemistry to investigate the expression of vascular endothelial growth factor in the epithelial and stromal cells of mammary phyllodes tumors. The correlation of vascular endothelial growth factor with tumor grade, stromal cell nuclear pleomorphism, cellularity, mitotic rate, margin histomorphology, and the stromal microvessel density was evaluated. Vascular endothelial growth factor expression was found in the epithelium in 29% and in the stromal cells in 31% of cases. There was significant increase of vascular endothelial growth factor expression in the stromal cells with increasing degree of malignancy, but not the epithelium. Microvessel density in the stroma also showed significant correlation with tumor malignancy, and a correlation was shown with the stromal vascular endothelial growth factor expression. Statistical overlap of stromal vascular endothelial growth factor and microvessel density in predicting malignancy suggests that angiogenesis may be an effector mechanism for vascular endothelial growth factor. Assessment of stromal VEGF may be useful as an adjunctive diagnostic criterion in the histologic assessment of malignancy in phyllodes tumors.     

Morphological Characteristics of the Retinomotor Response in Salmon Trout (<Emphasis Type="Italic">Oncorhynchus Masou</Emphasis>) Fry in a Magnetic Field and Red Light

The retinomotor response was studied in fry of the salmon trout Oncorhynchus masou during experimental exposures to a constant magnetic field and red light alone and together. The responses of photoreceptors and the pigmented epithelium to red light were mesopic in nature. The mesopic state of the retina after exposure of fish to a magnetic field in the dark differed from the pigment epithelium response after exposure to red light. On exposure to the magnetic field after red light, the effects of these two treatments were additive. Rods adapted to low-light conditions, while cones adapted to light. The simultaneous operation of these two mechanisms of perception is thus possible, although it never occurs in normal conditions. On exposure to red light after the magnetic field, the retinomotor response reflected a physiological dysfunction in which neither rods nor cones were operative. The pigmented epithelium is actively involved in responses to changes in the magnetic field. It is suggested that cells of the pigmented epithelium can function as light-sensitive magnetoreceptors. __________ Translated from Morfologiya, Vol. 126, No. 6, pp. 32–36, November–December, 2004. Director: Doctor of Biological Sciences S. L. Kondrashev