Congenital nevomelanocytic nevi: proportionate area expansion during infancy and early childhood.

BACKGROUND: The way in which congenital nevomelanocytic nevi (CNN) expand relative to anatomic region during growth is relevant to decisions about optimal timing for surgical excision and assessment for malignant change. OBJECTIVE: Our purpose was to determine how CNN area expands relative to anatomic region during infancy and early childhood. METHODS: Forty-one small CNN in as many subjects were studied from the newborn period. Relative area (CNN area/anatomic region area) was derived for each measure. Proportionate expansion (PE), defined as change in relative area per unit time as a proportion of initial relative area, was calculated. Relative to anatomic region, area expansion of CNN is greater when PE is greater than 0, less when PE is less than 0, and at least double when PE is +1.0 or greater. RESULTS: From the newborn period to last measure (2 to 71 months), PE ranged from -0.7 to +8.8 (median, +0.1). For 66% of CNN (27 of 41), PE was greater than 0. Nine of 39 CNN (15.4%) had PE values of +1.0 or greater during the first 6 months, compared with 1 of 26 cases (3.8%) for the interval beginning at or after 6 months. CONCLUSION: Disproportionately rapid area expansion of CNN may occur during early infancy, related to transient benign neoplasia, delayed pigmentation, and/or error of the methods used in the analysis.

Dysplastic nevi, cutaneous melanoma, and gynecologic disorders.

We compared the frequency of reproductive system diseases and disorders among 206 female patients with dysplastic nevi (DN), and/or melanoma, in comparison with random samples of women of comparable age without melanoma. The highest odds ratio (OR) for these age-related diseases and reproductive disorders occurs among the youngest age group of the patients with DN alone (mean age 35.1 +/- 1.2 yr): 44.2% of the DN subjects had one or more reproductive disorders compared with 19.8% of the random sample (OR 3.2, 95% CL (1.6, 6.5), P less than 0.001). The patients with melanoma and DN (mean age 41.5 +/- 1.4 yr) also had a significantly greater percentage of subjects with one or more reproductive disorders, though less so than the DN subjects: 49.4% compared to 33.7% (OR 1.9, 95% CL (1.1, 3.3), P = 0.02).

Sun-induced freckles in children and young adults. A correlation of clinical and histopathologic features.

Sun-induced freckles are a risk factor for epidermal and melanocytic neoplasia. Whereas sun-induced freckles in children and older adults may be clinically indistinguishable, and sun-induced freckles in older adults usually consist of increased numbers of intraepidermal melanocytes, the histology of sun-induced freckles in children remains unsettled. Using L-3,4 dihydroxyphenylalanine (DOPA)-paraffin sections, the authors examined six sun-induced freckles and adjacent nonpigmented skin (ANP) in as many white male subjects, ages 10 to 23 years. Melanocyte frequency was expressed as the ratio of DOPA-reactive melanocytes to total epidermal basal unit cells. For each case, melanocyte frequencies in freckles were significantly greater than in ANP. Cellular atypia of melanocytes was noticed in four of six freckles. Reactivity of melanocytes for HMB-45 was noticed in two freckles studied, compared with no reactivity in three specimens of ANP studied. The authors conclude the sun-induced freckles in the young may consist of a hyperplasia of melanocytes (i.e., similar to solar lentigines in the elderly), sometimes with cellular atypia, and that these findings may be relevant to melanocytic neoplasia.

Cutaneous melanoma and bilateral retinoblastoma.

We report the case of an otherwise healthy 37-year-old man who had had bilateral enucleation during early childhood for bilateral retinoblastomas, in addition to two cutaneous melanomas (the first appearing at age 27 years). He also had dysplastic melanocytic nevi and a history of cutaneous melanoma in his mother. Retinoblastoma may aggregate in families and is associated with DNA abnormalities of chromosome 13. Recent reports have emphasized the appearance of second malignancies in retinoblastoma survivors. The second malignancies include osteosarcoma, soft tissue sarcoma, and cutaneous melanoma. Cutaneous melanoma also may aggregate in families, usually in the setting of dysplastic melanocytic nevi. The features of this case and of similar reported cases suggest that there may be a greater than expected association between retinoblastoma and cutaneous melanoma.

Genital lentiginosis: a clinical and histopathologic study.

We studied the clinical and histopathologic characteristics of melanotic macules of the penis and vulva. The 10 lesions studied were relatively large (up to 2 cm), multifocal, irregular in outline, and had variegated pigmentation. Most were regarded as clinically atypical in appearance. Histologic examination of the lesions showed basal layer hyperpigmentation, slight melanocytic hyperplasia, epithelial hyperplasia, and stromal melanophages. No cytologic atypia of melanocytes was detectable. Information is insufficient at present to predict the natural history of genital lentiginosis or its relation to mucocutaneous melanoma.

Dysplastic melanocytic nevi and cutaneous melanoma: markers of increased melanoma risk for affected persons and blood relatives.

Dysplastic melanocytic nevi are potential precursors of cutaneous melanoma and markers of increased risk. This article presents representative case histories that illustrate the usefulness of careful follow-up of persons who have dysplastic melanocytic nevi or cutaneous melanoma, as well as examination of their blood relatives for the same lesions. Identification and periodic examination of such high-risk persons may result in the detection of melanoma in a curable phase. Our observations suggest that (1) dysplastic melanocytic nevi may aggregate in families of persons who have dysplastic melanocytic nevi or melanoma, even in the absence of a family history of dysplastic melanocytic nevi or melanoma and (2) formal genetic and natural history studies of persons who have dysplastic melanocytic nevi outside the familial melanoma setting are warranted.

Metastatic lentigo maligna melanoma.

An elderly woman presented with an advanced and ultimately lethal lentigo maligna melanoma after ignoring a precursor lesion present for several decades. Lentigo maligna melanoma can be lethal in the elderly. Early detection and treatment are warranted.

Metabolic Requirement of Cucurbita pepo for Boron.

Lateral roots of intact summer squash seedlings (Cucurbita pepo L.) were used to quantify the effects of boron deficiency on DNA synthesis, protein synthesis, and respiration. The temporal relationship between changes in these metabolic activities and the cessation of root elongation caused by boron deprivation was determined. Transferring 5-day-old squash seedlings to a hydroponic culture medium without boron for 6 hours resulted in a 62% reduction in net root elongation and a 30% decrease in the incorporation of [(3)H]thymidine into DNA by root tips (apical 5-millimeter segments). At this time, root tips from both boron-deficient and boron-sufficient plants exhibited nearly identical rates of incorporation of [(14)C]leucine into protein and respiration as measured by O(2) consumption. After an additional 6 hours of boron deprivation, root elongation had nearly ceased. Concomitantly, DNA synthesis in root apices was 66% less than in the boron-sufficient control plants and protein synthesis was reduced 43%. O(2) consumption remained the same for both treatments. The decline and eventual cessation of root elongation correlated temporally with the decrease in DNA synthesis, but preceded changes in protein synthesis and respiration. These results suggest that boron is required for continued DNA synthesis and cell division in root meristems.

Substrate influences human epidermal melanocyte attachment and spreading in vitro.

Previous culture systems for melanocytes have employed serum-supplemented medium and uncoated plastic dishes, prohibiting examination of possible substrate influences on cellular morphology and function. We now report, using a sensitive serum-free system and a quantitative procedure for evaluating cellular morphology, that modification of the plating surface affects human epidermal melanocyte attachment rate and subsequent morphology in vitro. Melanocytes attach and spread more rapidly on surfaces coated with fibronectin or Type I/III collagen or on surfaces previously conditioned by human keratinocytes, dermal fibroblasts, melanocytes, or melanoma cells than do melanocytes on untreated control surfaces. Type IV collagen and laminin, although minimally beneficial for cell attachment, do support a characteristic melanocyte morphology that differs from that seen either on the other coated surfaces or on uncoated plastic controls. Addition of fetal bovine serum at the time of inoculation has no appreciable effect on attachment but markedly improves cell spreading on untreated surfaces, while addition of nerve growth factor with or without serum to this system fails to affect cell attachment or spreading. Our data establish that human epidermal melanocytes are indeed capable of responding morphologically to substrate signals. The ability of several biochemically unrelated surfaces to enhance melanocyte attachment rate and spreading suggests that melanocytes have surface receptors with a variety of specificities. This work is relevant to the development of improved culture systems for melanocytes in vitro and to understanding melanocyte behavior in vivo.

Recovery of plant amines with carboxylic ion-exchange substrates and their subsequent analysis by thin-layer chromatography.

Two grades of carboxymethylcellulose (CMC) and five ion-exchange resins were compared for their effectiveness in recovering endogenous amines from plant extracts. If amine loss was to be limited to 10%, the H+ and Na+ forms of CMC could not be loaded with the solutes from more than 0.25 and 1.5 gram fresh weight (gfw) tissue per ml bed volume respectively. The corresponding ionic forms of a typical resin, Amberlite CG-50, would tolerate loadings ca. 5 X higher than this. However, it was then necessary to use very slow flow-rates (13 ml cm-2 h-1) for both applying and eluting the amines and, even so, they could not be quantitatively displaced from any resin tested, with the possible exception of Duolite C433. If the extract was acidic, maximum permissible loadings were reduced by a factor of 3 to 20, depending on substrate and ionic form. The composition of the amine fraction was essentially the same whatever substrate was used for its recovery and whatever percentage of it had been lost.

Synthesis, salvage, and catabolism of uridine nucleotides in boron-deficient squash roots.

Previous work has provided evidence that plants may require boron to maintain adequate levels of pyrimidine nucleotides, suggesting that the state of boron deficiency may actually be one of pyrimidine starvation. Since the availability of pyrimidine nucleotides is influenced by their rates of synthesis, salvage, and catabolism, we compared these activities in the terminal 3 centimeters of roots excised from boron-deficient and -sufficient squash plants (Cucurbita pepo L.). Transferring 5-day-old squash plants to a boron-deficient nutrient solution resulted in cessation of root elongation within 18 hours. However, withholding boron for up to 30 hours did not result in either impaired de novo pyrimidine biosynthesis or a change in the sensitivity of the de novo pathway to regulation by end product inhibition. Boron deprivation had no significant effect on pyrimidine salvage or catabolism. These results provide evidence that boron-deficient plants are not starved for uridine nucleotides collectively. Whether a particular pyrimidine nucleotide or derivative is limiting during boron deprivation remains to be examined.

Regulation of Pyrimidine Biosynthesis in Intact Cells of Cucurbita pepo.

The occurrence of the complete orotic acid pathway for the biosynthesis de novo of pyrimidine nucleotides was demonstrated in the intact cells of roots excised from summer squash (Cucurbita pepo L. cv. Early Prolific Straightneck). Evidence that the biosynthesis of pyrimidine nucleotides proceeds via the orotate pathway in C. pepo included: (a) demonstration of the incorporation of [(14)C]NaHCO(3), [(14)C]carbamylaspartate, and [(14)C]orotic acid into uridine nucleotides; (b) the isolation of [(14)C]orotic acid when [(14)C]NaHCO(3) and [(14)C]carbamylaspartate were used as precursors; (c) the observation that 6-azauridine, a known inhibitor of the pathway, blocked the incorporation of early precursors into uridine nucleotides while causing a concomitant accumulation of orotic acid; and (d) demonstration of the activities of the component enzymes of the orotate pathway in assays employing cell-free extracts.Regulation of the activity of the orotate pathway by end product inhibition was demonstrated in the intact cells of excised roots by measuring the influence of added pyrimidine nucleosides on the incorporation of [(14)C]NaHCO(3) into uridine nucleotides. The addition of either uridine or cytidine inhibited the incorporation of [(14)C]NaHCO(3) into uridine nucleotides by about 80%. The observed inhibition was demonstrated to be readily reversible upon transfer of the roots to a nucleoside-free medium. Experiments employing various radiolabeled precursors indicated that one or both of the first two enzymes in the orotate pathway are the only site(s) of regulation of physiological importance.

Early effects of boron deficiency on indoleacetic Acid oxidase levels of squash root tips.

The indoleacetic acid (IAA) oxidase activity of root tips of boron-sufficient, -deficient, recovering, and IAA-treated boron-sufficient squash plants (Cucurbita pepo L.) was determined. Apical and subapical root sections displayed an increase in IAA oxidase activity between 6 and 9 hours after boron was withheld, and after 24 hours the activity of the apical sections showed a 20-fold increase over +B controls. Root elongation of -B plants was inhibited before an increase in oxidase activity could be detected. Roots of plants subjected to 12 hours of -B treatment and then transferred to +B treatment for recovery regained normal elongation rates and oxidase activity within 18 to 20 hours. IAA treatment of +B plants increased IAA oxidase activity of apical and subapical root sections and also inhibited root elongation and caused symptoms similar to -B treatments.These results have demonstrated the earliest enzymic change for intact boron-deficient plants. The results are in agreement with the theory that boron deficiency symptoms may be the result of supraoptimal endogenous levels of IAA. These high levels of IAA may inhibit cell division and lead to an induction of the IAA oxidase enzyme.

Autoradiographic Examination of Meristems of Intact Boron-deficient Squash Roots Treated with Tritiated Thymidine.

Intact roots of boron-sufficient squash (Cucurbita pepo L.) plants, plants entering boron deficiency, and plants recovering from boron deficiency were exposed to tritiated thymidine at the end of the treatment period to label the replicating DNA of root tip cells. Using histological sections, autoradiographs of intact root meristems were prepared. The labeling pattern in +B root tips revealed the presence of a well defined quiescent center. The ability of root tip cells to incorporate label is correlated with the total root elongation during the -B treatment period. A greater amount of total root elongation during boron deficiency and recovery reflects the fact that root tip cells have retained their ability to synthesize DNA and enter mitosis for a longer time. In roots recovering from boron deficiency, cells of the quiescent center were seen to play no part in the recovery process in roots treated for as long as 20 hours in a -B nutrient solution. They were inactive before, during, and after the -B treatment. Cessation of mitosis occurs as early as 6.5 hours after boron is withheld from the nutrient solution while DNA synthesis can occur for as long as 20 hours after withholding boron. It was concluded that boron is essential for continued DNA synthesis and mitotic activity. The absence of boron results in the cessation of mitosis and DNA synthesis within 20 hours from the time boron is withheld.

Influence of Water Activity, Temperature, and Their Interaction on Germination of Verticillium albo-atrum Conidia.

Conidia were germinated at three temperatures in media in which available water, expressed as water activity, was controlled at three levels. Rate of germination in the basal medium (0.9964 water activity) was most rapid at 25 C and was inhibited at 15 and 30 C. Lowering the water activity at a particular temperature decreased rates of germination. However, at a low water activity (0.9778) germination rate was greater at 30 C than at 25 C. Thus, the effect of temperature on germination appears to be dependent on the water activity of the medium.

Effect of light intensity and plant size on rate of development of early boron deficiency symptoms in tomato root tips.

Young tomato plants (Lycopersicon esculentum Miller, cultivar Rutgers) grown in solution culture at 27 degrees at 2 light intensities with adequate boron (0.1 mg/l) and treated with these 2 intensities in the absence of adequate boron developed root boron deficiency symptoms. The typical deficiency symptoms of decreased root elongation, increased depth of brown color and decreased RNA content of tips developed more rapidly at high than at low light intensity, and plant size influenced results. Plants supplied with adequate boron did not exhibit deficiency symptoms.