bluuebunny/crossref_metadata_2025 huggingface dataset:
New Thioureas and Related Substances Intended for Melanoma Targeting
Authors: MÅRS ULLA , LARSSON BENGT S.
Published: July 2006

Thiouracil and a few related drugs are known to be melanoma‐seeking agents owing to specific incorporation into nascent melanin. The melanin‐affinic properties are apparently due to binding to intermediates, preferably dopaquinone, produced in the melanin synthetic pathway by tyrosinase‐catalysed oxidation of tyrosine.

In the present paper, in vitro screening methods have been used for the identification of possible melanoma seekers according to the above principle. The binding of test substance to dopaquinone suppresses dopachrome formation by the withdrawal of dopaquinone from the reaction mixture, and the decrease in dopachrome concentration was monitored spectrophotometrically at 475 nm. In order to eliminate false results caused by tyrosinase inhibition, which also will decrease the dopachrome concentration, the oxygen consumption was followed potentiometrically. To avoid the effect of tyrosinase inhibition on dopachrome formation, additional experiments with autoxidation of L‐dopa in the presence of test substance were performed. Of the 22 substances (mainly thioureylenes and thioamides) studied, 4,5,6‐triamino‐2(H)‐pyrimidinehtionsulfate, trithiocyanuric acid, 2‐thiouracil, 6‐methyl‐2‐thiouracil, and 4‐amino‐2‐mercaptopyrimidine most effectively decreased the dopachrome formation with no or little inhibition of tyrosinase activity. They should therefore be regarded as potential melanoma seekers. In a complementary autoradiographic study on the uptake of the potent tyrosinase inhibitor mercaptobenzothiazole (MBT) in B 16 melanoma, transplanted to mice, it was found that strong tyrosinase inhibition seems to decrease incorporation into melanin in vivo. MBT was partly accumulated in restricted areas of the tumor, which may be explained by the small molar dose injected.
Eumelanin and Phaeomelanin Contents of Human Epidermis and Cultured Melanocytes
Authors: HUNT GILLIAN , KYNE SYLVIA , ITO SHOSUKE , WAKAMATSU KAZUMASA , TODD CAROLE , THODY ANTHONY J.
Published: July 2006

There are two chemically distinct types of melanin: the red‐yellow phaeomelanins and the brown‐black eumelanins. While both melanins have been detected in human epidermis and cultured melanocytes, it is unknown how the phaeomelanin/eumelanin ratio in human melanocytes maintained in vitro relates to that in the epidermis from which they were isolated. This study uses high‐performance liquid chromatography to quantify the eumelanin and phaeomelanin contents of epidermis and/or cultured melanocytes from 12 Europeans with lightly pigmented skin and 9 non‐Europeans with more deeply pigmented skin. Epidermis from non‐Europeans contained the highest levels of both eumelanin and phaeomelanin and had the lowest phaeomelanin/eumelanin ratios. In contrast, while cultured melanocytes from non‐Europeans also had higher levels of eumelanin and phaeomelanin than melanocytes from Europeans, there was no difference in the phaeomelanin/eumelanin ratios in the two groups. However, the phaeomelanin/eumelanin ratios were higher in the cultured melanocytes than in the corresponding epidermis so that while eumelanin was the predominant melanin in the epidermis, phaeomelanin was the major melanin in the cultured melanocytes. These observations may have important implications for the use of cultured human melanocytes in the study of melanogenesis in man.
Effect of Kojic Acid on the Oxidation of DL‐DOPA, Norepinephrine, and Dopamine by Mushroom Tyrosinase
Authors: KAHN VARDA
Published: July 2006

Kojic acid inhibits effectively the rate of formation of pigmented product(s) and of oxygen uptake when DL‐DOPA, norepinephrine and dopamine are oxidized by mushroom tyrosinase. In addition to the direct effect of kojic acid on the enzyme, kojic acid also affects the UV‐VIS spectrum of the final product(s) formed, this being due to the ability of the o‐quinones of these substrates to oxidize kojic acid to a yellow product(s). Kojic acid can thus prevent the conversion of the o‐quinones of DL‐DOPA, norepinephrine and dopamine to their corresponding melanin.
The Pinkeyed‐Dilution Protein and the Eumelanin/Pheomelanin Switch: In Support of a Unifying Hypothesis
Authors: LAMOREUX M. LYNN , ZHOU BAO‐KANG , ROSEMBLAT SUSANA , ORLOW SETH J.
Published: July 2006

The two major types of mammalian melanin are pheomelanin (yellow or red pigment) and eumelanin (black or brown). The agouti (A) and extension (E) loci determine whether follicular melanocytes will deposit pheomelanin or eumelanin within their melanosomes. Mutations at the murine pinkeyed‐dilution (P) locus cause a striking reduction in deposition of eumelanic, but not pheomelanic, pigment. The mRNA encoded at the P locus is not expressed in skin that exclusively produces pheomelanic pigment as a result of mutation at the agouti locus.

We have suggested, based upon both genetic and biochemical evidence, that three key melanogenic proteins—tyrosinase, tyrosinase‐related‐protein‐1 (TRP‐1), and TRP‐2, encoded at the albino (C), brown (B), and slaty (Slt) loci, respectively—form a high‐molecular‐weight “melanogenic complex” within the melanosome. High‐molecular‐weight forms of tyrosinase, TRP‐1 and TRP‐2, are absent from eumelanic ocular tissues of pun/pun mice that fail to produce normal P‐locus transcript, even though these mice are genetically normal at the loci that regulate production of the three melanogenic proteins. We have hypothesized that the presence of the p‐locus protein is important for the integrity of the melanogenic complex and for the levels of members of the TRP family. We show here that the yellow skins of mice mutant at the agouti or extension loci, as well as the nonyellow skins of pinkeyed‐unstable (pun/pun) mice, demonstrate greatly diminished levels of tyrosinase, TRP‐1 and TRP‐2, and an absence or markedly decreased proportion of high‐molecular‐weight forms of melanogenic proteins.

We conclude that normal levels of wild‐type P‐locus protein are necessary for eumelanogenesis and that the absence of this protein may be necessary, but is not sufficient to cause the melanosome to switch to the production of pheomelanin. We discuss the implications of our results in relation to the interacting genetic controls regulating melanogenesis.
Composition of Mammalian Eumelanins: Analyses of DHICA‐Derived Units in Pigments From Hair and Melanoma Cells
Authors: WILCZEK ADAM , KONDOH HIROFUMI , MISHIMA YUTAKA
Published: July 2006

The proportions in which two eumelanin monomers, namely 5,6‐dihydroxyindole‐2‐carboxylic acid (DHICA) and 5,6‐dihydroxyindole (DHI), compose the eumelanin polymer are believed to determine properties of the pigment including its color. These proportions are, however, not well elucidated for naturally occurring eumelanins, largely because of methodological difficulties. In this study we estimate the content of DHICA‐derived units in mammalian eumelanins using a combination of two analytical techniques: 1) quantitation of DHICA‐derived eumelanin by measuring the yield of pyrrole‐2,3,5‐tricarboxylic acid (PTCA index) and 2) spectrophotometrical quantitation of total (DHI + DHICA) eumelanin at 350 nm (A350 index). The ratio of PTCA/A350 measured for melanins synthesized from DHI and DHICA mixed in various molar proportions correlates well with the content of DHICA in synthetic polymers. Using this relationship as a standard curve we estimated the proportion of DHICA‐derived units in mammalian eumelanins from hair and melanoma cells and found it to be much higher in rodent pigments (58.8%‐98.3%; two species, mouse and hamster were examined) as compared to human eumelanins (19.2%‐41.8%; one Caucasian and one Oriental individual were examined). No relationship between proportion of DHICA‐derived units in eumelanin and hair color is found. The latter seems to be determined predominantly by the ratio of pheo‐ to eumelanin synthesis.
On the Melanization of the Rat's Eye
Authors: ANSORGE MICHAEL , SAHLMANN BERND , STANKA PETER
Published: July 2006

Electron‐microscopic study of the size of the melanosomes, the mean percentage of melanosomal profile area (MPMA) of the cells, and the duration of melanogenesis in the pigmented layers of the rat's eye (inbred strain BDE/Han) revealed the following: 1) The melanosomes in the cells of the retina vary in size and shape in different locations of the eye. The MPMA of the cells also differs. Only in the two layers of the iris epithelium do the minor diameters of the melanosomes not differ significantly from each other, but the MPMA of the cells is different. The pigmented outer layer of the ciliary epithelium stands out on account of its especially large, round melanosomes. 2) The melanosomes of the uveal melanocytes are uniformly small but exhibit the largest MPMA. 3) Only in the pigment epithelium of the fundus does melanogenesis cease in the fifth week of life. As a result the MPMA decreases. In the other areas of the pigmented epithelium and the uvea tyrosinase activity and premelanosomes are present from the new‐born to the adult animal. These signs indicate continued melanogenesis. 4) Compound melanosomes are present in all pigmented locations of the eye. Giant melanosomes occur regularly only in the outer layer of the retina.
Melanomacrophage Aggregations and Their Age Relationships in the Yellow Mud Turtle, Kinosternon flavescens (Kinosternidae)
Authors: CHRISTIANSEN JAMES L. , GRZYBOWSKI JOHN M. , KODAMA ROBERT M.
Published: July 2006

Microscopic examination of the pigment cell aggregations in the liver and spleen of mud turtles (Kinosternon flavescens) suggests that the morphology and behavior of these cells is consistent with the melanomacrophages described in teleost fishes and the pigmented “Kupffer cells” described in frogs and reptiles. These cells contain massive amounts of melanin, substantial lipofuscin, and some hemosiderin consistent with their phagocytic function. Similar‐appearing isolated pigmented macrophages are solitary in the liver, spleen, lung, and kidney. Number and size of the largest hepatic aggregations increase almost linearly with turtle age so that in old turtles they may constitute up to 20% of the liver volume. This increase may result from hepatic recruitment of macrophages throughout the life of the turtle and suggests that size and number of melanomacrophage aggregations may serve as a marker for senescence in otherwise healthy turtles of this species.
Melanocortin Receptors: Identification and Characterization by Melanotropic Peptide Agonists and Antagonists
Authors: HADLEY MAC E. , HRUBY VICTOR J. , JIANG JIWEN , SHARMA SHUBH D. , FINK JODY L. , HASKELL‐LUEVANO CARRIE , BENTLEY DAVID L. , AL‐OBEIDI FAHAD , SAWYER TOMI K.
Published: July 2006

Hormones are chemical messengers released from cells to act on and control the activity of other cells. Hormonal ligands initiate their actions by interacting with receptive substances (Langley, 1906) of the target cells. These receptors are proteins that are either integral components of the cell membrane or are localized cytoplasmically within cells. Ligand‐receptor interaction results in either the stimulation or inhibition of cellular activity. Since most hormones bind rather specifically to receptors possessed by their target cells, labeling of hormonal ligands can be utilized to identify and localize cells within an animal. In this report we discuss what is presently known about melanocortin receptors (MCRs) as studied by the use of labeled melanotropic peptide ligands.
Detection of a Fine Lamellar Gridwork After Degradation of Ocular Melanin Granules by Cultured Peritoneal Macrophages
Authors: SCHRAERMEYER ULRICH , DOHMS MARIANNE
Published: July 2006

In the present study we investigated by electron microscopy whether melanin granules derived from choroidal melanocytes and retinal pigment epithelium of cattle could be degraded in the phagolysosomes of cultured murine macrophages. It was found that degradation of ocular melanin is possible by the lysosomes of these macrophages. During degradation of the melanin granules an internal gridwork of fine concentric, highly ordered membranes, 3‐4 nm thick, became visible. These membranes may represent remnants of the melanin polymer in the original melanosome or may result from self‐assembly of degradation products. Early‐stage melanosome‐like structures also appeared during digestion of these melanin granules. Melanin granules that seemed to break down into smaller fragments without any visible internal structure were also observed.
The Influence of Extracellular Matrix Proteins on Cutaneous and Uveal Melanocytes
Authors: HEDLEY S J. , WAGNER M. , BIELBY S. , SMITH‐THOMAS L. , GAWKRODGER D.J. , NEIL S. MAC
Published: July 2006

Cutaneous and ocular melanocytes are routinely cultured in complex mitogen‐rich media. The physiological regulation of melanocyte proliferation and differentiation is not yet fully defined and this study summarises several separate lines of evidence which suggest that, in vivo, some of the signals required for melanocyte proliferation and differentiation may derive from extracellular matrix (ECM) proteins adjacent to these cells. Culture of cutaneous and uveal melanocytes on cell‐derived and individual ECM proteins was found to influence cell morphology with such effects being most noticeable in mitogen‐deficient media. Similarly, cell‐derived and individual ECM proteins increased tyrosinase activity in normal cutaneous melanocytes and effects of these ECM proteins were seen most consistently in mitogen‐deficient media. Uveal melanocytes (as has been reported for cutaneous melanocytes) showed preferential attachment to fibronectin over other ECM substrates. This attachment was particularly sensitive to drugs which affected intracellular calcium or calmodulin activity. Acute addition of fibronectin to coverslips of uveal melanocytes loaded with Fura‐2 produced an acute and transient increase in intracellular calcium which was more prevalent in low density than higher density cells. We conclude that ECM proteins in vitro are capable of influencing melanocyte morphology, tyrosinase activity, and proliferation and that an ECM‐induced elevation in intracellular calcium may be part of the signalling system that transmits ECM information into the cell.
Sequence Analysis of the Human Tyrosinase Promoter From a Patient With Tyrosinase‐Negative Oculocutaneous Albinism
Authors: MATSUNAGA JUN , DAKEISHI MIWAKO , MIYAMURA YOSHINORI , TOMITA YASUSHI
Published: July 2006

We examined the tyrosinase gene from a patient with tyrosinase‐negative oculocutaneous albinism (OCA). First we studied the protein coding region, exon/intron junctions, and the proximal promoter region (positions ‐300 to +1) of her tyrosinase gene by direct sequencing. Although the results showed that she was heterozygote for the R77Q mutation, we could find no other mutation. To find a second mutation and compare the sequence in the 51‐flanking region of her tyrosinase gene between two OCA alleles, we amplified a 2422‐bp stretch (positions ‐2065 to +357, including R77Q mutation site) by PCR, and cloned it into a plasmid vector. As a result, we discovered a difference between two OCA alleles in the GA repeat region. Therefore, we expect that the polymorphism in the GA repeat region of the tyrosinase gene will be used as a flanking marker of the OCA allele.
Electron Transfer and Photoprotective Properties of Melanins in Solution
Authors: MENTER JULIAN M. , WILLIS ISAAC
Published: July 2006

The polyquinoid nature of eumelanin(s) enables them to couple oxidation of electron donors with the reduction of electron acceptors. We have studied the ability of synthetic (Sigma) and “biological” (cuttlefish sepia) melanins to mediate electron transfer between hydroxybenzene donors (tyrosine, dopa, chemical depigmenters) and model acceptors (ferricyanide, tyrosinase). 1) Depending on the reductant, melanin either retards or accelerates ferricyanide reduction. Reaction kinetics are consistent with a mechanism involving non‐interactive binding of both hydroxybenzene and ferricyanide to melanin prior to coupled electron transfer. 2) Melanins also act as an electron conduit in markedly accelerating the tyrosinase‐catalyzed oxygenation of p‐hydroxyanisole (MMEH). The active species appears to be a complex between melanin and MMEH. The magnitude of both effects depend on the type of melanin as well as its oxidation state.

Sepia (eu)melanin appears to protect against UV‐induced damage to acid‐soluble collagen, as judged by irreversible loss of intrinsic collagen fluorescence. Photoprotection against this type of damage appears primarily to involve optical absorption/scattering by the pigment.
Multiple α2‐Adrenoceptor Signalling Pathways Mediate Pigment Aggregation Within Melanophores
Authors: SVENSSON SAMUEL P.S. , ADOLFSSON PER I. , GRUNDSTRÖM NILS , KARLSSON JAN OLOF G.
Published: July 2006

It has previously been shown that α2‐adrenoceptors (α2‐ARs) mediate pigment granule (melanosome) aggregation in melanophores of the teleost fish Labrus ossifagus. The present investigation scrutinized the signalling mechanisms of melanosome aggregation induced by sympathetic nerve stimulation or by exogenous addition of α‐AR agonists and cAMP analogues. The following was observed: i) nerve‐induced melanosome aggregation was associated with a rapid decrease in the cAMP level; ii) noradrenaline or medetomidine (an α2‐AR agonist) caused melanosome aggregation and reduced the cAMP content; iii) RP‐S‐CI‐cAMP, a membrane‐permeating inhibitor of protein kinase A induced melanosome aggregation; and iv) B‐HT 920 (an α2‐AR agonist) and methoxamine (an α1‐AR agonist) induced melanosome aggregation, although they did not reduce cAMP.

It has been suggested that in some teleost species α1‐ARs mediate melanosome aggregation by increasing the level of intracellular calcium. However, we found that the effect of methoxamine in melanophores from Labrus ossifagus could be blocked by yohimbine (an α2‐AR antagonist) but not by equimolar concentration of prazosin (an α1‐AR antagonist). Furthermore, 1 μM ionomycin (a calcium ionophore) did not induce melanosome aggregation. Our findings therefore do not indicate that α1‐ARs and/or an increase in intracellular calcium mediate melanosome aggregation in Labrus ossifagus.

Our results suggest that α2‐AR‐mediated melanosome aggregation is induced by multiple signalling pathways. One of these involves a reduction in cAMP, but none involves an increase in intracellular calcium.
The Role of Melanocytes in the Repair of UV Related DNA Damage in Keratinocytes
Authors: IYENGAR BHANU
Published: July 2006

Epidermal pigmentation and UV exposure are related to the incidence of skin tumors. There is a higher incidence of UV related skin tumors in populations with low pigment and in vitiligo patients, resulting from DNA damage. Normally DNA repair processes set in with the expression of PCNA in the keratinocyte.

The present study was conducted on the marginal zone skin in vitiligo. Whole skin organ cultures irradiated with increasing doses of UV in the 280–400 nm range show that in the depigmented area there is no expression of PCNA by the keratinocytes. In comparison, the marginal zone keratinocytes show a dose related positivity in the presence of UV responsive melanocytes. These photoresponsive melanocytes show dendricity and cytoplasmic PCNA positivity. The melanocytes interact with keratinocytes by active melanosome transfer. From this study it is suggested that this involves transfer of PCNA as well.

The present study indicates the differentiating keratinocytes in skin do not express PCNA but appear to be dependent on active UV responding melanocytes for DNA repair. This factor could play an important role in the occurrence of UV‐related skin tumors.
Reptilian Melanomacrophages Function under Conditions of Hypothermia: Observations on Phagocytic Behavior
Authors: JOHNSON JAMES C. , SCHWIESOW TYLER , EKWALL ALICIA K. , CHRISTIANSEN JAMES L.
Published: July 2006

Melanomacrophages (MMs) were removed from livers of turtles of three North American families and cultured. J774 mammalian macrophages were similarly cultured and the MMs were exposed to E. colifluor at approximately 2, 7, 27, and 37°C. At least one third of the MMs continued to function at the low temperatures where less than 2% of the mammalian cells incorporated bacteria deeply into the cytoplasm. In most instances, when the bacteria were not internalized deeply into the cytoplasm, they became stationary just inside, or within, the cell membrane. The MMs were significantly less efficient than the mammalian cells at 37°C and significantly more efficient at 2 and 7°C. In general, it appears that MMs are never as efficient as mammalian macrophages under the most ideal temperatures for the cell but they are capable of functioning at reasonable levels at temperature extremes. The observations are suggestive of a genetic mechanism functioning in the MMs that is rarely expressed in J774 cells under conditions of hypothermia. MMs in vitro and probably in vivo consume bacteria, fungi, attach to helminth eggs, and consume old erythrocytes.
Functional Characterization of a Receptor for Vasoactive‐Intestinal‐Peptide‐Related Peptides in Cultured Dermal Melanophores from Xenopus laevis
Authors: MAROTTI LOUIS A. , JAYAWICKREME CHANNA K. , LERNER MICHAEL R.
Published: July 2006

A receptor for vasoactive‐intestinal‐peptide (VIP)‐related peptides was functionally characterized in a cell line derived from Xenopus melanophores using a recently described microtiter‐plate‐based bioassay. Activation of the melanophore VIP receptor by VIP or the peptides pituitary‐adenylate‐cyclase‐activating polypeptide (PACAP 38), PACAP 27, and helodermin stimulated intracellular 3′‐5’cyclic adenosine monophosphate (cAMP) accumulation and pigment dispersion in the cells. Helodermin, with an EC50 (concentration of peptide inducing halfmaximal melanosome dispersion) of 46.5 pM, was the most potent activator of pigment dispersion, followed by PACAP 38 > VIP > PACAP 27. A similar order of potencies was observed for the peptides to induce cAMP accumulation. The responses to VIP agonists were selectively inhibited by the VIP antagonists PACAP‐(6‐27) and (N‐Ac‐Tyr1‐D‐Phe2)‐growth‐hormone‐releasing factor[GRF](1‐29)‐NH2. Taken together, the results suggest that the melanophores express a VIP receptor that shares certain characteristics of, but also differs significantly from, other previously identified VIP receptors.
Current Understanding on the Role of Retinal Pigment Epithelium and its Pigmentation
Authors: Schraermeyer Ulrich , Heimann Klaus
Published: July 2006

Retinal pigment epithelium (RPE) is a monolayer of cuboidal cells that is strategically placed between the rod and cone photoreceptors and the vascular bed of the choriocapillaris. It has many important functions, such as phagocytic uptake and breakdown of the shedded photoreceptor membranes, uptake, processing, transport and release of vitamin A (retinol), setting up the ion gradients within the interphotoreceptor matrix, building up the blood‐retina barrier, and providing all transport from blood to the retina and back. This short review focuses on the role of the pigment granules in RPE. Although the biology of the pigment granules has been neglected in the past, they do seem to be involved in many important functions, such as protection from oxidative stress, detoxification of peroxides, and binding of zinc and drugs, and, therefore, serve as a versatile partner of the RPE cell. Melanin plays a role in the development of the fovea and routing of optic nerves. New findings show that the melanin granules are connected to the lysosomal degradation pathway. Most of these functions are not yet understood. Deficit of melanin pigment is associated with age‐related macula degeneration, the leading cause of blindness.
Chemical Analysis of Melanin Pigments in Feather Germs of Japanese Quail Bh (Black at Hatch) Mutants
Authors: SHIOJIRI NOBUYOSHI , NIWA TOHRU , WAKAMATSU KAZUMASA , ITO SHOSUKE , NAKAMURA AKIRA
Published: July 2006

Bh (black at hatch) is a mutation of Japanese quails which causes darkening or lightening of the plumage in heterozygotes or homozygotes, respectively. We chemically analyzed melanin pigments in feather germs of Bh mutant embryos and in feathers of adult animals. Dark brown dorsal feathers of wild‐type adult animals had white barrings, but heterozygous ones lacked clear barrings. The feathers of wild‐type and heterozygote animals contained both eumelanins and pheomelanins, the latter being more pheomelanic. On the dorsal skin of 10‐day old wild‐type embryos, longitudinal stripes from black and yellow rows of feather germs developed; two or three longitudinal rows of black feather germs and then two or three rows of yellow feather germs next to the short central feather germs. Heterozygous embryos appeared black in plumage pigmentation, due to the presence of‘gray’feather germs in rows of dorsal feather germs that corresponded to yellow rows in wild‐type embryos. Homozygous dorsal feather germs did not develop the black and yellow longitudinal stripes, but were brown. Chemical analysis showed that embryos of each genotype contained both eumelanins and pheomelanins in the feather germs; however, the eumelanin content in ho‐mozygous feather germs was very low. These results suggest that the Bh mutation causes pheomelanic changes in feathers of quails.
Identification of Microtubule‐Organizing Centers in Interphase Melanophores of Xenopus Laevis Larvae In Vivo
Authors: RUBINA KSENIYA A. , GULAK PAVEL V. , SMIRNOVA ELENA A. , STARODUBOV SERGEI M. , ONISHCHENKO GALINA E.
Published: July 2006

The morphological characteristics of microtubule‐organizing centers (MTOCs) in dermal interphase melanophores of Xenopus laevis larvae in vivo at 51‐53 stages of development has been studied using immuno‐stained semi‐thick sections by fluorescent microscopy combined with computer image analysis. Computer image analysis of melanophores with aggregated and dispersed pigment granules, stained with the antibodies against the centrosome‐specific component (CTR210) and tubulin, has revealed the presence of one main focus of microtubule convergence in the cell body, which coincides with the localization of the centrosome‐specific antigen. An electron microscopy of those melanophores has shown that aggregation or dispersion of melanosomes is accompanied by changes in the morphological arrangement of the MTOC/centrosome. The centrosome in melanophores with dispersed pigment exhibits a conventional organization, and their melanosomes are situated in an immediate vicinity of the centrioles. In melanophores with aggregated pigment, MTOC is characterized by a three‐zonal organization: the centrosome with centrioles, the centrosphere, and an outlying radial arrangement of microtubules and their associated inclusions. The centrosome in interphase melanophores is presumed to contain a pair of centrioles or numerous centrioles.

Because of an inability of detecting additional MTOCs, it has been considered that an active MTOC in interphase melanophores of X. laevis is the centrosome. We assume that remaining intact microtubules in the cytoplasmic processes of mitotic melanophores (Rubina et al., 1999) derive either from the aster or the centrosome active at the interphase.
Lymphatic and Blood Vessels of the Aged Human Gingiva1
Authors: Bernick Sol , Sobin Sidney S.
Published: July 2006

The lymphatic pathways in the gingivae from aged humans were traced by the use of the PAS reaction or iron hematoxylin stain, and their structural characteristics were compared to those of the blood microvasculature. In the young and aging gingivae the lymphatic capillaries originated in the connective tissue papillae of the lamina propria, and appeared as thin walled irregular shaped vessels. The adjacent blood capillaries in aged gingivae differed in that their walls were thicker and stained intensely Schiff positive than seen in young adult gingivae. The lymphatic capillaries emptied into thin walled collecting vessels of varying calibers that course through the lamina propria to reach the main conducting vessels that contained valves projecting within its lumen. The accompanying blood vessels were easily differentiated from the lymphatic vessels by the intense positive staining of their walls following exposure to the PAS reaction. Distended lymphatic vessels of different caliber were demonstrable in inflamed aging gingivae, suggesting that lymphatic vessels in the aged gingivae were able to provide a drainage system for excessive fluid, proteins, and other particulates from both non‐injured and injured sites.
Age‐Related Changes in EGF and Protease in Submandibular Glands of C57BL/6J Mice1,4
Authors: Gresik Edward W. , Brennan Michael , Azmitia Efrain
Published: July 2006

The submandibular glands of male C57BL/6J mice were studied cytologically and chemically at the following ages (months): 1–1.5, 6–8, 12–13, 28–32. The relative proportion of granular convoluted tubules (GCT) as well as the size and content of secretion granules of GCT cells, progressively increased throughout the first year of life. Correspondingly, the concentration within the glands of two GCT cell products, epidermal growth factor (EGF) and protease, also steadily increased. In senescent glands, GCTs formed relatively less of the gland parenchyma and were composed of shorter cells with reduced amounts of secretory granules. The concentration of EGF was reduced to 17% of its peak value at one year, while protease activity declined to 50% of its peak value. These morphologic and chemical findings imply a functional impairment in submandibular glands of the mouse with senescence.
The Measurement of Biological Age1,4
Authors: Ludwig Frederic C. , Smoke Mary E.
Published: July 2006

One of the objectives of gerontological research is to achieve, reproducibly and at will, a verifiable discrepancy between the chronological and biological age of organisms. To accomplish this, the experimenter must be in a position to measure biological age independently. In theory, this can be done in three ways: by actuarial analysis of large populations, assessment of overall morbidity, or observation of chronic degenerative changes that can be actually measured or graded according to a scale. Of these three approaches, only the last appears to be promising in experimental research. However, not all progressive degenerative changes represent practically useful parameters of biological age. Criteria for their evaluation are presented, and their theoretical prerequisites as well as concrete applications are discussed. In a more general way, one has to be aware that biological age is a statistical entity. It cannot be directly observed but only inferred from quantifiable epiphenomena, and is, as such, not measurable like temperature or weight.
The Epidemiology of Dental Diseases in the Elderly1
Authors: Beck James D.
Published: July 2006

This paper summarizes and evaluates epidemiologic evidence on adult dental conditions with a focus on older adults. Information is presented on coronal caries; root caries; loss of teeth, attrition, abrasion, and erosion; periodontal diseases; and oral cancer. The author concludes that the oral health status of the elderly in the United States is essentially unknown. There are no recent, representative population base studies of oral conditions in the elderly. Studies of prevalence or incidence of oral diseases typically include few elderly persons or describe a select group of elderly who are at high risk. Furthermore, it is not really known whether the incidence and prevalence of coronal caries or root caries is actually increasing or is part of a cohort effect. While oral cancers have been shown to increase with age, there is no information as to whether their incidence rates are increasing. While, clinically, there are indications that attrition, abrasion and erosion are characteristics that are more likely to be seen in older adults, there is no information about their distribution in the population. There is evidence that loss of teeth is decreasing but nothing is known about the patterning of that loss. As for periodontal diseases, much work is needed to identify various syndromes that may be distinguished by their distribution in the population as well as determining whether periodontitis is a condition responsible for a majority of tooth loss or just the majority of tooth loss in a small high risk group. In addition, some suggestions are presented for future directions of research in this area.
Aging Effects on Anatomy and Neurophysiology of Taste and Smell1
Authors: Mistretta Charlotte M.
Published: July 2006

Taste and smell have a primary role in food ingestion. Therefore, to understand why eating habits alter in elderly people, age‐related differences in the chemical senses should be investigated. In early anatomical studies, substantial decreases in numbers of taste buds in old human and mouse circumvallate papillae were observed. However, recent investigations in humans, monkeys, and rats indicate that there is not a significant loss of taste buds in old age. Neurophysiological recordings from the chorda tympani nerve, innervating taste buds in fungiform papillae, demonstrate significant but small differences in response magnitudes for some chemicals in old rats. Greater age‐related differences have been observed in the olfactory sense. Numbers of receptor neurons in the rat olfactory epithelium initially increase in adults and then decline in old animals; this decline is reflected in subsequent changes in the olfactory bulb. However, numbers of synapses in the bulb per receptor neuron are increased in the oldest rats, suggesting some compensatory mechanism. Differences in degree of aging effects in taste and smell might relate to the nature of receptors: a modified epithelial cell in taste versus a neuron in smell. However, in both sensory systems, large numbers of receptors remain even in old age. Since taste bud cells and olfactory receptors turn over and are replaced throughout life, the peripheral taste and smell systems might be relatively resistant to aging effects.
A Reference Guide to Drugs and Dry Mouth
Authors: Sreebny Leo M. , Schwartz Steven S.
Published: July 2006

Dry mouth (xerostomia) is a common complaint which occurs in about 25% of the elderly. Drugs play a principal role in its etiology. This REFERENCE GUIDE is designed to help the practitioner identify the medicaments which may cause this condition. Moreover, it offers suggestions for the treatment of drug‐induced dry mouth.
The Clinical Profiles of Individuals With and Without Root Surface Caries1
Authors: DePaola P.F. , Soparkar P.M. , Tavares M. , Kent R.L.
Published: July 2006

As part of a collaborative multidisciplinary investigation of root surface caries (RSC), 273 subjects (median age = 57) were clinically evaluated for coronal caries, debris, calculus, gingivitis, periodontal pocketing, recession, abrasion, as well as RSC. The entire study group was divided into three subgroups: (1) subjects whose exposed root surface were without lesions or restorations (non‐diseased individuals, n= 43); (2) subjects whose exposed root surfaces had one or more lesions and may or may not have had restorations (diseased individuals, n= 110); (3) subjects with one or more restorations but no lesions, since it was not known whether these restorations were preceded by RSC or abrasion the disease status of these individuals was unclear (n= 120). A comparison of Subgroup 1 (unequivocally non‐diseased) and Subgroup 2 (unequivocally diseased) revealed that subjects without RSC had more teeth, less coronal caries, less recession, less debris, less calculus, less gingivitis, and more abrasion. We infer that the common factor underlying most if not all of the subgroup differences is oral hygiene which must therefore be a major disease determinant.
Gerodontology—A Contemporary Prosthetic Challenge Part 1: Mandibular Impression Technique
Authors: Mersel Alex
Published: July 2006

In geriatric complete denture prosthodontics, several factors may contribute to the failure of the prosthetic device. The piezography technique, a special functional approach is described in order to overcome the difficulties of the mandibular denture.
Measurement of the Force Required to Extract the Mandibular First Molar from Its Socket in the Dissected Jaw of Growing Young Rats
Authors: Komatsu K. , Ohshima S. , Chiba M.
Published: July 2006

Age‐related changes in the mechanical strength of the periodontal ligament have been examined by measuring the force required to extract the mandibular first molar from its socket at an extension rate of 5 mm/min in the dissected jaws of growing young rats from 3 to 32 weeks of age. Almost linear increase in the ultimate loads was found from 3 to 8 weeks of age. However the values from 8 to 32 weeks of age did not show any significant differences. Close correlations were found between the ultimate loads and the weights of animals, mandibles and extracted teeth and between the load and length of the tooth from 3 to 8 weeks of age. It is supposed that a mechanical equilibrium has been established within the periodontal ligament in association with various external and internal factors such as root elongation, alveolar bone growth, turnover and maturation of periodontal ligament and occlusal activity, at about 8 weeks of age in the rat mandibular first molar.
Endodontic Considerations When Fabricating Overdentures
Authors: Goodis Harold E. , Curtis Donald
Published: July 2006

Successful use of an overdentures prosthesis depends on the successful completion and maintenance of endodontically‐treated teeth. The process of completion and maintenance of teeth so treated in elderly individuals is difficult and less predictable. The purpose of this paper is to discuss treatment considerations to enhance success when treating elderly candidates for endodontic overdenture abutment retention.
Oral Findings in Elderly Nursing Home Residents in Selected Countries. I.
Authors: Pietrokovski Jaime , Tamari Israel , Mostavoy Robert , Levy Fanny , Azuelos Yosef , Tau Shmuel
Published: July 2006

In order to determine the influence of culture, individual idiosyncrasy, social and economic conditions as well as the importance of past and current dental care on oral health, the oral conditions of 610 patients in seven old age homes were evaluated in four countries: USA, Peru, Argentina and Israel. The patients included in this study were examined by clinicians who had undergone training and calibration sessions. The seven institutions surveyed have a large range of physical facilities, economic levels, and a variety of quantity and quality among medical, dental and ancillary staff. There were marked differences as to philosophy of treatment and scope for the dental care of the residents. A subjective impression by the examiners is that old age home administrators do not regard the dental needs of the residents to be among their higher priorities. Dental care is considered expensive and requires special equipment and exclusive physical space on the institutional premises. Of the 610 residents 419 were women and 191 men, with an average age of 80 years. The mean number of years of schooling was six. Sixty‐two percent of the examinees were widowed, 21% were married, 1% single, 2% divorced, and 5% of unknown or undeclared status. The main orodontal characteristic of the population surveyed was partial or full eduentulousness. Of the total population (610 examinees) only three patients possessed a full complement of natural, unrestored teeth. Twelve examinees had 28 unit dentition, partly natural teeth and partly restored with plastic fillings, fixed prostheses, crowns or pontics. Three hundred and one patients (49%) of the examined population were totally edentulous. 249 (41%) wore sets of complete dentures and 52 (8%) did not wear any prosthetic restoration or replacement.
Medical and dental status of a culture in transition, the case of the Inuit elderly of Canada
Authors: Galan Douglas , Odlum Olva , Grymonpre Ruby , Brecx Michel
Published: July 2006

The medical and dental status, and drug utilisation pattern of Canadian Inuit elders (60+years) were evaluated. Inuit elders averaged 6.3 medical conditions per person, primarily nervous system‐sense organ deficits, respiratory problems and systemic infections. The mean number of drugs being used was 2.5 per person, primarily analgesics, bronchodilators and antibiotics. Poorly fitting dentures, and high levels of tooth decay, periodontal disease, soft tissue and TMJ anomalies were documented. Compared to older southern Canadians, the medical and dental findings for these Inuit elders were different. Drug utilisation rates were consistent with older southern Canadians, but different drugs were taken.
Future directions for root caries research
Authors: Billings Ronald J. , Banting David W.
Published: July 2006

Interest among researchers in the diagnosis, aetiology, prevention, and treatment of root caries has increased substantially over the past two decades. However, there are some fundamental problems impeding the advancement of the field which remain to be addressed and resolved. A universally acceptable definition of root caries is not yet available. The relationship of root caries to coronal caries has not been established. The underlying disease process is still not clearly understood. The optimal utilisation of preventive/therapeutic agents for the treatment or prevention of root caries has not been determined. New treatment materials and preventive agents have not yet been tested in controlled clinical trials. These are a few of the issues and problems which we address in this paper.
Osteoporosis and the jaws: questions remain to be answered
Authors: Lockington T.J. , Bennett G.C.J.B.
Published: July 2006

Osteoporosis is a major health issue in later life, which translates the age‐associated increased risk of falls into a hip, shoulder or wrist fracture. The same pathology may result in vertebral crush fracture after minor loading of the axial skeleton. The health burden is enormous. Over a five year period, 10% of the female population of the United Kingdom, over 70 years of age, will suffer a fractured femoral neck, from which up to 20% may die and only a third of the survivors will be fully mobile at six months1.
Estimates of time and propensity for dental treatment among institutionalised elders
Authors: Mojon Philippe , MacEntee Michael I.
Published: July 2006

The oral health and concerns of elderly residents were surveyed in a stratified random selection of 41 long‐term care facilities in Vancouver. The residents who could participate were examined and interviewed to determine their oral health and concerns about dental treatment. The need and time required for treatment were estimated in six groups to reflect the propensity for treatment in dentate and edentate subjects. The propensity for treatment was high in about one‐third of the participants whereas it was unlikely that one‐tenth of those examined would ever use a dental service. In general, there was a widespread need for a diagnostic service because so few had been examined by a dentist in the previous year. Prosthodontics accounted for most of the treatment in all of the propensity groups, with substantially more time required by the dentate residents. There was also a substantial need for management of mucosal pathoses and oral hygiene and, to a lesser extent, for dental restorations and endodontics. Overall, our estimates indicate a substantial need for dental treatment among residents of long‐term care facilities, although the need is reduced by half if the propensity for treatment is considered.
Oral status and well‐being of home delivered meal recipients
Authors: Long H. Lewis , Miller William A.
Published: July 2006

The relationship between oral health status and well‐being of community dwelling frail elders was studied through questionnaires delivered to and filled out by 592 elders receiving home delivered meals. Oral status covered oral function, dental problems, oral hygiene practices and appliance use in the sample. Oral status was measured in a sub sample of 50 subjects given an oral examination, using the criteria above and soft tissue status. Plaque, calculus, and caries were measured in dentate subjects of the sub sample. Well‐being was measured using standardised scales. The results indicate that oral status was related to well‐being status.
Whole saliva and the diagnosis of Sjögren's syndrome: an evaluation of patients who complain of dry mouth and dry eyes. Part 1: Screening tests
Authors: Sreebny Leo , Zhu Wan Xing
Published: July 2006

Sjögren's Syndrome (SS) is a common autoimmune disorder characterised by generalised desiccation, exocrine hypofunction and serologic abnormalities, More than 90% of the patients are women. Objective: to determine if whole saliva could be used to diagnose this disease. Setting:The study was conducted at the School of Dental Medicine, SUNY, at Stony Brook. Patients: There were 49 subjects (48F; 1M), the mean age was 54 ± 13 years. In order to be admitted into the study, they had to complain of dry mouth and dry eyes. Tests: Whole saliva was collected by the spitting method. “Screening Tests'” were employed to measure the salivary flow rate, pH, buffer capacity; lactobacillus and yeast concentrations. Chemical tests were performed to determine protein, albumin, sodium and amylase activity. Lacrimal dryness was assessed by the Schirmer and Rose‐Bengal methods. Results:Based on the sialometric findings, the patients were divided into 3 groups: Group 1: those with abnormally low resting (RFR) and stimulated (SFR) flow rates; Group 2: those with a low RFR but normal SFR; and Group 3: those with normal salivary flow rates. The group 1 patients were unique: their saliva demonstrated a low pH and buffer capacity, high lactobacillus and yeast concentrations, decreased protein output and amylase activity, and elevated albumin and sodium. Moreover, virtually all of them had abnormally low lacrimal flow rates. Conclusions: The findings suggested that whole saliva could be used to provisionally diagnose SS. Critical to this diagnosis was an abnormally low stimulated whole saliva flow rate. Other requisites included a low resting flow rate, the presence of dry mouth and dry eyes and evidence of lacrimal hypofunction. All of these attributes can easily be obtained by dentists in their clinics.
Measuring the impact of oral health in old age: a qualitative reaction to some quantitative views
Authors: MacEntee Michael I.
Published: July 2006

Investigations into the oral health‐related beliefs and behaviour of old people are complex and fraught with methodological difficulties. They have employed to a large extent structured interviews or questionnaires based on the Sickness Impact Profile to explain the impact of oral disorder in old age. However, despite sophisticated statistical techniques, the results have failed to explain much of the variance in the responses of the elderly subjects. This paper reviews the results of several investigations conducted in a structured and quantitative manner, and contrasts them with an alternative method of inductive investigation using a more qualitative interpretation of open‐ended interviews. The alternative method of exploration with a small but intensely involved group of elderly participants revealed a view of oral health that reflects a willingness of elders to adapt constructively to changes in the mouth with advancing age. Moreover, the construction of a framework of oral health‐related beliefs and behaviours that emerged from the qualitative analysis of open‐ended interviews, has widened our understanding of the significance of the mouth in old age beyond the framework of biophysical, functional and disabling variables that dominated previous research on this field