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PubMed1989

The asymptotic transectional/circumferential homogeneity of the solutions of reaction-diffusion systems in/on cylinder-like domains.

It is often reported that an animal with spotty coat markings on its body has a tail with stripe-shaped pattern. In other various biological and chemical phenomena in/on cylinder-like domains, longitudinally periodic band patterns are observed much more often than the other non-uniform patterns. This paper mathematically explains these observations by proving that, in/on a long and narrow cylinder-like domain, any solution of reaction-diffusion system asymptotically loses its spatial dependence in the transectional/circumferential direction.

Animals↗
PubMed1995

The SMXA: a new set of recombinant inbred strain of mice consisting of 26 substrains and their genetic profile.

A new set of recombinant inbred (RI) strain SMXA consisting of 26 substrains was established between SM/J and A/J. The history of the SMXA RI strains and their genetic profile covering 158 genetic marker loci are reported. From the strain distribution pattern among SMXA RI strains, the chromosomal location of salivary and tear protein genes Spe1-r, Spe1-s, Spe2, and Tpe1 were newly determined.

Animals↗
PubMed1993

Chlorpromazine in human scalp hair as an index of dosage history: comparison with simultaneously measured haloperidol.

The concentration of chlorpromazine (CPZ) in hair was measured to demonstrate its value as an index of individual dosage history and compliance. An animal study using pigmented rats was conducted to confirm the dose-dependent accumulation of CPZ in hair. The concentration of CPZ in hair, newly regrown on a denuded area of the back after the administration of CPZ for 3 weeks, was 4.6, 8.5 and 16.6 ng.mg-1 hair after daily doses of 1.25, 2.5 and 5 mg.kg-1.day-1, respectively, significantly correlated with the daily dose. The concentration of CPZ in black hairs collected from 23 Japanese patients, who had been taking CPZ in fixed daily doses (30-300 mg/day), ranged from 1.6 to 27.5 ng.mg-1, and was significantly correlated both with the daily dose and with the trough plasma concentration at steady state. Several strands of hair collected from each of 5 patients, whose doses of CPZ had been changed within several months before sampling, were cut into 1-cm pieces successively from the scalp end and the concentration of CPZ in each piece was measured. With the assumption of a hair growth rate of 1 cm per month, the individual history of CPZ doses in all patients could be deduced from the distribution of CPZ along the hair shaft. In 5 patients with grizzled hair the concentration of CPZ in white hairs was much lower (< 10%) than in black hairs, suggesting that the strong affinity of CPZ for hair melanin may explain the accumulation of CPZ in black hair.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

A high-resolution linkage map of the lethal spotting locus: a mouse model for Hirschsprung disease.

Mice homozygous for the lethal spotting (ls) mutation exhibit aganglionic megacolon and a white spotted coat owing to a lack of neural crest-derived enteric ganglia and melanocytes. The ls mutation disrupts the migration, differentiation, or survival of these neural crest lineages during mammalian development. A human congenital disorder, Hirschsprung disease (HSCR), is also characterized by aganglionic megacolon of the distal bowel and can be accompanied by hypopigmentation of the skin. HSCR has been attributed to multiple loci acting independently or in combination. The ls mouse serves as one animal model for HSCR, and the ls gene may represent one of the loci responsible for some cases of HSCR in humans. This study uses 753 N2 progeny from a combination of three intersubspecific backcrosses to define the molecular genetic linkage map of the ls region and to provide resources necessary for positional cloning. Similar to some cases of HSCR, the ls mutation acts semidominantly, its phenotypic effects dependent upon the presence of modifier genes segregating in the crosses. We have now localized the ls mutation to a 0.8-cM region between the D2Mit113 and D2Mit73/D2Mit174 loci. Three genes, endothelin-3 (Edn3), guanine nucleotide-binding protein alpha-stimulating polypeptide 1 (Gnas), and phosphoenolpyruvate carboxykinase (Pck1) were assessed as candidates for the ls mutation. Only Edn3 and Gnas did not recombine with the ls mutation. Mutational analysis of the Edn3 and Gnas genes will determine whether either gene is responsible for the neural crest deficiencies observed in ls/ls mice.

Animals↗
PubMed1995

Molecular markers near two mouse chromosome 13 genes, muted and pearl, which cause platelet storage pool deficiency (SPD).

The recessive muted (mu) and pearl (pe) mutations on Chromosome (Chr) 13 cause pigment dilution and platelet storage pool deficiency (SPD) in mice. In addition, mu causes inner ear abnormalities and pe has symptoms associated with night blindness. Using an interspecific backcross involving the wild-derived Mus musculus musculus (PWK) stock, we have mapped 33 microsatellite markers and four cDNAs relative to mu, pe, and another recessive mutation, satin (sa). Analyzing a total of 528 backcross offspring, we found tight linkage between the pigment loci and several microsatellite markers (D13Mit87, D13Mit88, D13Mit137 with mu; and D13Mit104, D13Mit160, D13Mit161, and D13Mit169 with pe). These markers should aid the eventual molecular identification of these specific SPD genes.

Animals↗
PubMed1986

Position of Igl-1, md, and Bst loci on chromosome 16 of the mouse.

The experiments described here delineate the position of the chromosome 16 markers Igl-1 (immunoglobulin lambda 1, light chain), md (mahoganoid), and Bst (belly spot and tail), and suggest their location relative to the endogenous proviral locus Akv-2, which is linked within 5.9 centimorgans to Igl-1 (Epstein et al. 1984). The data from an intercross and a three-point backcross detailed herein show the order of these three genes and distances between them to be: centromere-md-10.4 +/- 1.6-Igl-1-15.6 +/- 2.6-Bst. Using a recombinant chromosome recovered in the intercross, we have constructed a stock homozygous for md and Igl-1b (KpnI-), that will aid in mapping other genes on chromosome 16.

AKR murine leukemia virus↗
PubMed1995

The impact of dietary fats, photoperiod, temperature and season on morphological variables, torpor patterns, and brown adipose tissue fatty acid composition of hamsters, Phodopus sungorus.

We investigated how dietary fats and oils of different fatty acid composition influence the seasonal change of body mass, fur colour, testes size and torpor in Djungarian hamsters, Phodopus sungorus, maintained from autumn to winter under different photoperiods and temperature regimes. Dietary fatty acids influenced the occurrence of spontaneous torpor (food and water ad libitum) in P. sungorus maintained at 18 degrees C under natural and artificial short photoperiods. Torpor was most pronounced in individuals on a diet containing 10% safflower oil (rich in polyunsaturated fatty acids), intermediate in individuals on a diet containing 10% olive oil (rich in monounsaturated fatty acids) and least pronounced in individuals on a diet containing 10% coconut fat (rich in saturated fatty acids). Torpor in P. sungorus on chow containing no added fat or oil was intermediate between those on coconut fat and olive oil. Dietary fatty acids had little effect on torpor in animals maintained at 23 degrees C. Body mass, fur colour and testes size were also little affected by dietary fatty acids. The fatty acid composition of brown fat from hamsters maintained at 18 degrees C and under natural photoperiod strongly reflected that of the dietary fatty acids. Our study suggests that the seasonal change of body mass, fur colour and testes size are not significantly affected by dietary fatty acids. However, dietary fats influence the occurrence of torpor in individuals maintained at low temperatures and that have been photoperiodically primed for the display of torpor.

Adipose Tissue, Brown↗
PubMed1984

Tyrosine uptake in normal and albino hairbulbs.

A method for measuring tyrosine uptake by human hairbulbs was developed to further characterize the process of melanin formation in human tissue. Uptake was determined by incubating fresh anagen hairbulbs in 14C-tyrosine in HEPES-Tris buffer containing cycloheximide and catalase. Uptake for 11 normally pigmented subjects with brown, black, blond and red hair ranged from 295 cpm/24 h per hairbulb for hairbulbs from a blond subject to 6661 cpm/24 h per hairbulb for hairbulbs from a red-haired subject. Hairbulbs from a type IIA (tyrosinase-positive) oculocutaneous albino had an uptake of 2995 cpm/24 h per hairbulb. White hairbulbs had an uptake of 265 cpm/24 h per hairbulb. There was a good correlation (r = 0.86) between the level of uptake and the level of tyrosinase (tyrosine hydroxylase) activity when these values were compared for ten subjects. Uptake was reduced with the inhibition of tyrosinase activity. Uptake was also reduced with low incubation temperatures (4 degrees and 21 degrees C) and with the addition of unlabeled tyrosine to the incubation. From 14% to 19% of the 14C-tyrosine that was taken up could be extracted as 14C-melanin. These results show that the uptake of tyrosine as determined by this experimental method is dependent on the presence of melanocytes and tyrosinase, is quantitatively related to the level of tyrosinase activity, and appears to be a metabolic process. Type IIA albino hairbulb melanocytes appear able to transport adequate amounts of substrate.

Albinism↗
PubMed1987

Synthesis of cysteinylphenol, cysteaminylphenol, and related compounds, and in vivo evaluation of antimelanoma effect.

Phenolic and catecholic compounds were synthesized, by combination with cysteine or cysteamine through thioether bond, and their antimelanoma and melanocytotoxic effects were evaluated. Among nine compounds tested, 4-S-cysteaminylphenol (CAP) resulted in an increase in the life span (% ILS) of melanoma-bearing mice and in the growth inhibition (% GI) of melanoma tissue. 4-S-Cysteinylphenol (CP) and its methyl ester form also showed some increase in % GI. The 2-S-isomers of CP and CAP and diphenolic derivatives of CP did not show any significant antimelanoma effect. In addition, the s.c. injection of 4-S-CAP and 4-S-CP, in particular 4-S-CAP, caused the depigmentation of black hair which was manifested by loss of functioning melanocytes, as seen under light microscopy. The 4-S-CAP appears to provide a basis for development of a new class of antimelanoma and melanocytotoxic agents that are more stable than catecholic compounds, which have been most widely utilized as a source of rational chemotherapy for malignant melanoma.

Animals↗
PubMed1975

Function of the pancreatic B-cell during the development of hyperglycaemia in mice homozygous for the mutations "diabetes" (db) and "misty" (m).

The function of the pancreatic B-cell was studied in relation to the development of the diabetic syndrome in a new variety of the diabetic mutant mouse, which was produced at The Jackson Laboratory, Bar Harbor, Maine, U.S.A. by outcrossing of a c57bl/ksJ-db stock with C57BL/6J mice. The expression of the db-gene in the resulting strain was evaluated by measurements of the body weights and the concentrations of serum glucose and serum insulin at different ages of the animals. In the diabetic mice the body weights increased rapidly between 5 and 25 weeks of age to a weight twice that of the lean controls. During the same time hyperglycaemia and hyperinsulinaemia occurred, the maximal serum glucose and insulin values being observed between 17 and 25 weeks of age. Later on the serum glucose and serum insulin concentrations gradually decreased. Islets were isolated with collagenase from animals 5, 10 or 20 weeks old, and studied with respect to insulin content, glucose oxidation and the secretion and synthesis of insulin. The results were compared with data from control experiments with islets isolated from non-diabetic littermates. No major differences were found between islets from diabetic and control mice with regard to the glucose oxidation rate, whereas an exaggerated insulin response to glucose was observed in islets from 5 weeks old diabetic mice. In the 20 weeks old diabetic animals there was a significantly decreased islet insulin content and a considerably lowered insulin biosynthesis.

Age Factors↗
PubMed1978

Action of the "nude" gene on pigmentation of the coat in c57 black and c3 mice.

The authors have studied pigmentary changes of skin and hair due to the presence of the "nude" gene in pigmented species (C 57 Bl. 6J, C3H). Morphological (histology, electron microscopy) and biochemical (polyacrylamide gel electrophoresis of tyrosinase activities) studies showed that the pigmentary alterations of the "nude" mice were related to hair cycle and hair growth wave pattern. In fact, in the "nude" mice the hair follicles evolves cyclically similarly to mice of normal coat. In depigmented skin, the hair follicles were in the resting phase and no soluble tyrosinase could be demonstrated.

Animals↗
PubMed1984

Linkage of diabetes insipidus and agouti genes in the rat.

Linkage of the hooded (h), agouti (A), and diabetes insipidus (di) genes was found in (ACI X DI)F1 X DI backcross rats. The genetic map distance A-di for females and for males was 19 +/- 5 and 28 +/- 5 cM, respectively. However, this difference was not significant. The combined data showed the map distance to be 25 +/- 4 cM. The three-point cross showed the following corrected distances and order of genes: h-42 +/- 4-A-25 +/- 4-di. However, the linkage of h and A, although significant (chi 2 = 9.03, P less than 0.001), is only tentative and must be confirmed by additional studies.

Animals↗
PubMed1977

[Comparative investigations of depigmented and melanomatous lesions in gray horses of the lipizzaner breed (author's transl)].

The morphological substrates of pigmented and depigmented skin as well as the structural characteristics of spontaneously developing melanomas were revealed by clinical, light- and electron microscopic methods in gray horses (Lipizzaner breed) from the Vienna Spanish Riding School. On clinical investigations in a group of 31 older horses (more than 10 years old) 20 exhibited melanomas, whereas 23 younger animals (less than 10 years of age) had no evidence for visuable melanotic tumors. Concomitantly with the progressive graying of the hair a depigmentation of the skin was frequently observed. Light and electron microscopic studies of skin biopsies revealed that in pigmented areas melanin is produced by DOPA-positive melanocytes and stored in form of large single melanosomes within keratinocytes. In depigmented areas melanocytes and melanosomes are completely lacking, but a high number of indeterminated cells is present in the basal layer. Melanotic tumors from the root of the tail, the lips, the perianal region, the sholder and intestinal lymph nodes exhibited either encapsulated nodules or diffusely infiltrating melanomatous structures similar to blue nevi in the dermis. Junctional activity could never be observed. A differentiation between melanin-producing tumor cells and melanophages was difficult in light microscopy but possible according to ultrastructural characteristics.

Aging↗
PubMed1977

Hereditary deafness in the cat. An electron microscopic study of the stria vascularis and Reissner's membrane.

The auditory pathway potentials have been recorded from a series of 35 cats, and the stria vascularis and Reissner's membrane examined with the electron microscope. The ages varied from the first postnatal day to at least 6 years. 30 of the animals had white coats, and 45 of the ears lacked potentials. The basal processes of the marginal cells fail to develop in pathological ears, and appear displaced towards the endolymphatic surface by a layer of grossly swollen, chromophobe cells. These features are already present at the 3 day stage, and persist until the third week. Thereafter, increasing electron density of all cell types is found, with progressive reduction in strial thickness. Swelling of the capillary endothelial cells and descent of Reissner's membrane are found in the first coil at 2 weeks. Obliteration of capillaries, and development of vacuolar cytoplasmic outgrowths from the vestibular membrane mesothelial cells occur at later stages. These findings are discussed and compared with the pathological changes produced by a variety of endogenous 2nd exogenous factors in both man and animals.

Animals↗
PubMed1990

Bone marrow transplantation (BMT) for the syndrome of pigmentary dilution and lymphohistiocytosis (Griscelli's syndrome).

We report the successful treatment of the syndrome of pigmentary dilution and immunodeficiency (Griscelli's syndrome) with allogeneic bone marrow transplantation. Griscelli's syndrome includes silvery hair, recurrent infections, hepatosplenomegaly, progressive neurologic deterioration, and lymphohistiocytosis and is uniformly fatal. We present a family in which four of seven children of consanguinous parents were affected. The affected children were all born with silvery hair. Microscopic examination of the hair showed large clumps of pigment in the hair shaft. Skin biopsy revealed an accumulation of melanosomes in the melanocytes. Three of the affected children were deceased before 20 months of age. Pathology of liver and lung in two of the siblings showed an infiltration of lymphocytes and histiocytes. Immunologic studies in one of these cases were notable for a decreased number of T cells and poor T-cell mitogen stimulation with concanavalin A (Con A) and pokeweed mitogen (PWM). Recently, a fourth sibling with silvery gray hair was referred to us at 3 months of age for evaluation. T-cell function studies were normal and she appeared in overall good health. Because of the expected fatal outcome, allogeneic bone marrow transplantation was performed at 4 months of age. Two years later the patient remains in excellent health. This suggests that cells of hematopoietic origin are responsible for the fatal outcome in Griscelli's syndrome and that bone marrow transplantation early in the course of the disease is an important modality for treatment of this syndrome.

Bone Marrow Transplantation↗
PubMed1990

Effects of the microphthalmic white gene on audiogenic seizure susceptibility in mice.

Audiogenic seizure susceptibility was studied in mice segregating for the microphthalmic white gene (Miwh). Previous work by Deol had indicated that mice with either one or two Miwh alleles had severe inner ear defects. A congenic inbred strain provided mice that were identical in genetic background except for single-gene substitutions at the microphthalmia locus. The three genotypes tested were Miwh/Miwh, Miwh/+, and +/+. Mice were exposed to the sound stimulus once for a 1-min period between the ages of 17 and 30 days. Heterozygous Miwh/+ mice had more seizures and were more reactant than either type of homozygote at all ages tested. Responses were low at 17 days of age, peaked sharply by 23 days, and declined markedly by 30 days.

Acoustic Stimulation↗