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Biomedical subjects

B Iyengar

Publications and source records attributed to B Iyengar.

At least 19 recordsLinked to original sources

Corticotropin expression by human melanocytes in the skin.

Highly dendritic melanocytes have been observed in rapidly proliferating seborrheic keratosis, epidermis overlying melanomas, and in melanomas. On staining for the presence of POMC with monoclonal antibody against human ACTH, the melanocytes show cytoplasmic positivity. Short term organ cultures of whole skin from the marginal zone of vitiligo patients show that 22.7% of controls and 45.5% on dark incubation in adriamycin and 87.5% exposed to a pulse of UV on adriamycin treatment show melanocytes positive for ACTH. The surrounding keratinocytes in the epidermis and in the seborrheic keratosis are negative, whereas in melanomas, isolated groups of melanocytes are positive for ACTH. These findings indicate that ACTH is expressed by the melanocytes in the G2-phase, the activity being enhanced on UV exposure. Thus UV dependent pigmentation is associated with POMC production in human skin. From this work it is evident that the melanocyte network varies the MSH/ACTH levels in correlation with repigmentation and depigmentation in the marginal zone in vitiligo by expressing POMC locally and is related to the UV-sensitivity of the melanocytes.

Adrenocorticotropic Hormone

Aspirin by virtue of its acidic property may act as teratogen in early chick embryo.

Aspirin (acetylsalicyclic acid) was dissolved either in normal saline or in phosphate buffer and was used in two doses to find out whether teratogenic potential of aspirin in chick blastoderm model is due to its acidic property or due to drug action. Drug was injected sub-blastodermally by window technique in fresh embryonated eggs after 17 hours of incubation at 39 degrees C. Eggs were re-incubated and harvested at 40 hours. Normal development of embryos was seen with normal saline and percentage of normal embryos with 30 micrograms (pH-3.19) and 120 micrograms (pH-2.64) aspirin was 31.7 and 4.9 respectively. Buffer produced 80.8% normal embryos and buffered 30 micrograms (pH-6.87) and 120 micrograms (pH-6.69) aspirin produced 67.7% and 30.8% normal embryos respectively. Changing the pH of aspirin to near neutral decreased the defect induced by aspirin but a significant effect of aspirin was observed at higher dose which could be independent of pH action.

Abnormalities, Drug-Induced

Indoleamines and the UV-light-sensitive photoperiodic responses of the melanocyte network: a biological calendar?

The pineal, serotoninergic and pigmented neurons are associated with light-dependent sleep/arousal, serving as a biological clock with a circadian rhythm. This rhythm is maintained by melatonin which serves to recognise the 'dark' phase. The neural network that responds to seasonal variations in day/night length has not been identified. The present study demonstrates that melanocytes in human skin respond to changes in the duration of UV exposure, and can serve as a biological calendar. These responses are mediated by two indoleamines, serotonin and melatonin. Higher melatonin levels correspond to long nights and short days (short UV pulse), while high serotonin levels in the presence of melatonin reflect short nights and long days (long UV exposure). This response recapitulates the sleep/arousal patterns in animals exposed to large variations in day/night cycle that cause changes in coat colour from pure white in winter to complete repigmentation in summer.

Biopsy

UV guided dendritic growth patterns and the networking of melanocytes.

Whole skin organ cultures of vitiliginous skin show that the marginal melanocytes are highly sensitive to a pulse of UV exposure (210-380 nm) during the G2 phase of the cell cycle, as seen by prominent dendricity. Melanocytes are highly dendritic in the epidermis overlying rapidly growing tumors, as well as within proliferative lesions such as basal cell carcinomas and aggressive seborrheic keratosis. In the organ cultures the dendrites extend towards the source of UV, i.e. the surface, while the main body lies along the basement membrane. The epidermal melanocytes overlying tumors lie almost vertically, dendrites aligned towards the underlying tumor on one side and the surface on the other. Within tumors dendritic elongation is guided by mitotic and PCNA positive (S-phase) tumor cells, which are a source of ultraweak UV emissions in the range of 210-330 nm. These observations indicate that ultraweak biophoton emissions from neighbouring cells can simulate environmental cues and contribute to the plasticity of networks such as the melanocytes or the visual pathways.

Basal Cell Carcinoma

Expression of proliferating cell nuclear antigen (PCNA): proliferative phase functions and malignant transformation of melanocytes.

The UV-dependent G2-phase functions of melanocytes include dendricity, the expression of melanocyte stimulating hormone (MSH) receptors and neural differentiation. The present report studied highly dendritic melanocytes in epidermis overlying tumours, seborrhoeic keratosis, basal cell carcinoma and melanomas. The expression of the proliferative protein PCNA was studied by immunohistochemistry, as this indicates cells in S/G2-phase. In the non-neoplastic dendritic melanocytes, PCNA is retained in the cytoplasm, resulting in the arrest of the cells in the S/G2-phase for prolonged periods, as indicated by the length and complexity of the dendritic processes. In melanomas, this barrier is overcome with rapid proliferation of the cells and loss of dendricity. PCNA is produced in the cytoplasm and transported into the nucleus during the S-phase, as observed in melanomas. The arrest of melanocytes in the S/G2-phase for long periods associated with UV responsiveness makes these cells vulnerable to DNA damage and neoplasia. Pools of PCNA in the cytoplasm, when transported into the nucleus, would support the rapid proliferation observed in melanomas.

Biological Transport

Mechanism of aspirin induced neural tube defect in chick embryo.

The effect of acetyl salicylic acid (aspirin) on neural tube development in chick embryo was studied, using the chick embryo blastoderm model. Aspirin was injected in four different doses sub-blastodermally into fresh embryonated eggs. The role of PGE1 and PGE2 alpha in the defect induced by aspirin on neural tube development in chick embryo was studied. PGE1 (5 micrograms) given after aspirin (30 micrograms) treatment was found to produce greater defect in development. All the four doses of aspirin used (i.e., 6, 30, 60 and 120 micrograms/embryo) produced significant changes (P < 0.01) in the neural tube development of chick embryo. Pre-treatment with PGE1 did not modify the defect induced by aspirin, whereas pre-treatment with PGF2 alpha prevented neural tube defects induced by aspirin. It appears that aspirin (in the doses used) affects neural tube formation by decreasing PGF2 alpha synthesis in chick embryo blastoderm.

Alprostadil

Neural differentiation as an expression of UV sensitivity of melanocytes.

The present work is to study neural differentiation in melanocytes in relation to the cell cycle and UV exposure. Whole skin organ cultures of vitiliginous skin were exposed to a pulse of UV with and without prior Adriamycin treatment. It was observed that the highly dendritic marginal melanocytes are destroyed on UV exposure during the depigmentation phase but not during repigmentation. The melanocytes are resistant to UV destruction during the G2 phase as seen on Adriamycin treatment. They show a prominent increase in dendricity as well as biphasic activity to produce increased melanin and noradrenaline. Thus, the melanocytes form a UV-sensitive neural network in the skin. These responses are reminiscent of the repigmentation and depigmentation of coat color in animals exposed to extreme variations in the day/night cycles as seen at the poles.

Cell Differentiation

Melanocytes--a UV-sensitive neural network and circadian rhythms.

The melanocytes are acutely sensitive to a single pulse of UV and express neural differentiation. The present work was undertaken to observe whether the melanocyte can sense variations in the duration of UV exposure. Whole skin organ cultures from marginal zone in vitiligo were exposed to a single pulse of UV, 30, 60, 90 and 120 s each. Catecholoxidase levels in the marginal melanocytes and the volume of melanocytes were used to calculate and quantitate the changes in enzyme production. The melanocytes' dendricity, volume and enzyme production increases with the duration of UV exposure. This sensitivity of the marginal melanocytes, to changes in the duration of UV exposure, simulates the coat color changes in weasels and the polar fox exposed to extreme variations in the day/night cycles. The UV response is associated with proliferation of melanocytes as it is G2-phase dependent. Thus the melanocytes form a UV-sensitive neural network responding to annual changes in the photoperiodicity.

Catechol Oxidase

Proliferating trichilemmal cysts over the vulva.

A sixty-year-old woman with multiple proliferating trichilemmal cysts over the vulva is described. The appearance of the eruptions suggests a hamartomatous origin. The lesions in the later stages resembled basal cell carcinoma. The malignant potential of the cysts and their treatment are discussed.

Biopsy

Hypomelanosis of ito: histochemical and ultrastructural observations.

Skin biopsies were taken from an infant girl with Hypomelanosis of Ito (Incontinentia Pigmenti Achromians) for histopathological, histochemical and electron microscopic studies. Histological observations were similar to those reported previously. Electron microscopy revealed two groups of melanocytes, an effete group and another group with a highly dendritic appearance. The significance of these findings is discussed.

Female

Modulation of melanocytic activity by acetylcholine.

Acetylcholine esterase (AChE) activity is lowered in vitiliginous skin. The AChE activity in 52 cases of vitiligo during repigmentation and depigmentation has been observed in this study. The cases with marginal dendritic melanocytes show that AChE is negative in these cells during depigmentation but positive on repigmentation. There is little variation in activity in the cases showing nondendritic marginal melanocytes. Acetylcholine (ACh) has an inhibitory effect on dopa oxidase activity in both types of marginal melanocytes in vitiligo. ACh modulates pigment production by the melanocytes, its role being inhibitory. From the present results, it is evident that a fall in AChE activity in the melanocytes leads to greater inhibition by ACh aggravating the process of depigmentation in vitiligo.

Acetylcholine

Hair cycle and the histogenesis of pillar tumours.

In a study of 50 tumours of pilar origin, it was observed that tumours arise from each cell type depending upon the phase of the hair cycle. Thus nevoid lesions arise from the pluripotent cells of the early anagen phase; tumours from the hair matrix, outer root sheath and inner root sheath arise during the anagen phase, and the keratoacanthomas during the interphase between anagen and telogen. Basal cell epitheliomas can arise at any phase. It was observed that the tumours arising during the anagen phase from the fully differentiated follicles formed the bulk (88%) and the keratoacanthoma simulating the catagen/telogen phase was rare in consonance with the length of each phase. It is proposed that the inner root sheath tumours be named trichilemmomas and the outer root sheath tumours trichochlamydomas to distinguish them from one another.

Hair

Neural differentiation of melanocytes in vitiliginous skin.

Biopsies from 74 cases of vitiligo were examined to study the reactions of marginal melanocytes. In 35 cases, the melanocytes at the edge of the patch appeared highly dendritic and large with marked arborization of the dendrites between the surrounding epidermal cells. These cells showed low pigmentation but a high enzyme activity which extended along the dendrites. The enzymes include tyrosinase/dopa oxidase, dopamine oxidase and noradrenaline activity, indicating that these cells have a biphasic melanogenic/adrenergic differentiation. This similarity between the dendritic melanocytes and the amelanotic melanoma cell line HT-18 is of interest.

Cell Differentiation

Cupric ions and DOPA oxidase activity in melanocytes.

The inhibition of DOPA oxidase activity by cupric ions has been quantitated in cases of vitiligo showing dendritic and non-dendritic melanocytes at the margins. Cupric sulphate was added to the substrate solution, containing a reacting quantity of 12.12 micrograms of DOPA, to give 42.8 micrograms, 85.6 micrograms, 128.4 micrograms and 171.2 micrograms of cupric ions. Control slides were incubated with DOPA alone as substrate. On cytospectrophotometric analysis it was seen that the initial level of enzyme activity determines the type of inhibition curve. Thus, there is a gradual fall in activity with dendritic melanocytes which have a very high enzyme content, whereas the non-dendritic melanocytes show complete inhibition with one dose. It was observed that 15.75 micrograms of cupric ions were reduced by 12.12 micrograms of DOPA. The enzyme activation by cupreous ions is countered by the enzyme inhibition by cupric ions, the rate of inhibition being determined by the level of cupric ions.

Catechol Oxidase

The biphasic nature of a human amelanotic melanoma tumour line HT-18.

The morphological features of a human amelanotic melanoma tumour line, HT-18 was studied in vitro. Primary cultures show that the tumour cells are biphasic with respect to their differentiation as revealed by light microscopy, SEM and TEM. Most of the cells show numerous processes resembling neuronal dendrites. The cytoplasm contains stage I and II melanosomes, occasionally melanosomes showing irregular pigmentation. According to these observations it appears that the HT-18 cells are at an earlier phase of differentiation showing both melanogenic and neurogenic activity.

Animals

Reaction of dendritic melanocytes in vitiligo to the substrates of tyrosine metabolism.

Frozen sections of vitiliginous skin were treated with the substrates involved in melanogenesis and adrenergic activity to study the effect of changing chemical milieu on the biphasic dendritic melanocytes. The substrates used are tyrosine, DOPA, tyrosine + DOPA, dopamine, adrenalin and cupric ions. It was observed that tyrosine when used alone has a weak melanogenic reaction while DOPA and tyrosine + DOPA show a prominent activity. Adrenalin and dopamine inhibit the neural limb and enhance melanogenesis. Cupric ions on the other hand enhance the neural limb and inhibit melanogenesis. These changes are not evident in the non-dendritic melanocytes. Thus the highly dendritic melanocytes are at a lower state of differentiation. These biphasic cells are more sensitive to changes in the chemical milieu.

Copper