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PubMed1985

Combined effect of herpes simplex virus and tobacco on the histopathologic changes in lips of mice.

In the present study we have examined the combined effect of HSV-1 inoculation and tobacco application (snuff water extract or smoking tar condensate) on the histopathologic changes of mouse labial mucosa. Two months' exposure to tobacco or HSV-1 inoculation alone did not induce dysplasia in the epithelium of labial mucosa, while HSV-1 inoculation combined with snuff water extract or smoking tar condensate produced epithelial dysplasia and other histomorphologic changes (that is, hyperkeratosis, increased granular cell layer thickness, acanthosis, and increased inflammatory cell infiltration in a significant number of animals). This result indicates that HSV-1 and tobacco could possibly act synergistically in the development of precancerous oral lesions and oral cancer.

Animals↗
PubMed1994

Multifocal papilloma virus epithelial hyperplasia.

Multifocal papilloma virus epithelial hyperplasia is an infection of the oral mucosa produced by human papilloma virus types 13 and 32, which primarily bilaterally affects lips, lateral borders of tongue, and buccal mucosa. The attached oral mucosa, floor of mouth, soft palate, and oropharynx are sites that appear not to be affected. This study comprises 110 patients with multifocal papilloma virus epithelial hyperplasia identified over a period of 3 years in Guatemala City and neighboring rural areas. All but four patients were younger than 18 years of age. More than one affected patient was observed in several families. All but three cases occurred in patients living in extreme poverty (annual family income less than $1,200 in U.S. dollars). Biopsies of 60 lesions demonstrated acanthosis and nuclear degeneration within the epithelium. We suggest that the eponym Heck's disease be abandoned because this disease was described in the Latin-American literature before the initial description in the American literature. We propose the term multifocal papilloma virus epithelial hyperplasia, which best describes the nature and multifocality of this disease.

Adolescent↗
PubMed1976

Bilharziasis of urinary bladder and ureter: comparative histopathologic study.

The relative incidence and intensity of oviposition in schistosomiasis in different layers of both the urinary bladder and the ureter are presented. Histopathological changes in both organs are elucidated. Oviposition was heaviest in the submucosa of the urinary bladder, while the muscle layer was affected in 15% of specimens. Oviposition was mainly periureteral and in outer muscle layer of the ureter, and was present in only 22% in the ureteral submucosa. Epithelial changes, namely, Brunn nests, cystitis glandularis, cystitis cystica, and squamous metaplasia, were more marked in the bladder specimens than in the ureteral specimens. Squamous cell papilloma and squamous metaplasia associated with acanthosis of the bladder specimens were identified. Results indicate unanimously that the heavy deposition of ova in the submucosa of the bladder leads through its mechanical and toxic irritation to marked epithelial and premalignant changes which pave the way for the disturbing frequency of carcinoma of the bladder in the bilharzial patients which is not the case in the ureter.

Humans↗
PubMed1990

Insulin-resistant diabetes associated with partial deletion of insulin-receptor gene.

The insulin-receptor genes from a 16-year-old girl with type A insulin resistance, who presented with fasting hyperinsulinaemia, acanthosis nigricans, and reduced insulin binding, and from her family were examined. One allele of her insulin-receptor gene inherited from her mother contained a 1.2 kb deletion arising from a recombination between two Alu elements. The deletion removed the 14th exon in the beta subunit and altered the reading frame, to produce a stop codon after aminoacid 867. Pedigree analysis indicated that this mutation alone will not cause diabetes, and the proband is possibly a compound heterozygote. 4 other members of her family were heterozygous for the same mutation; all 4 had a decrease in insulin binding and slight impairment of glucose tolerance. Perhaps the same mutation is an underlying feature of some cases of non-insulin-dependent diabetes mellitus.

Adolescent↗
PubMed1984

Gingival hyperplasia caused by nifedipine--a preliminary report.

We observed marked gingival hyperplasia, similar clinically and histologically to the hyperplasia caused by 5:5 sodium diphenylhydantoin (Dilantin) during the last 18 months in five patients treated by nifedipine. Histologically, marked epithelial hyperplasia-acanthosis, with moderate inflammatory reaction in the lamina propria, was observed in all the biopsy specimens. Evidence points to a strong relationship between the gingival hyperplasia and the administration of nifedipine.

Aged↗
PubMed1991

Ultrastructural observations on 'foam cells' and the source of their lipid in verruciform xanthoma.

Verruciform xanthomas occur on mucocutaneous surfaces and are characterized by hyperkeratosis, acanthosis, and the occurrence of "foam cells" stuffed with lipid surrounding capillaries in the dermis between rete pegs. Ultrastructural examination of a lesion on the penis revealed the presence of melanocytes with many lipid droplets in the basal layer of the epidermis. We suggest that they are a major source of the lipid of the "foam cells." However, this study provides no information as to the nature or lineage of the "foam cells."

Foam Cells↗
PubMed1992

The sign of Leser-Trélat in a young woman with osteogenic sarcoma.

The sign of Leser-Trélat refers to a sudden increase in size and number of seborrheic keratoses associated with internal malignancy. The validity of this cutaneous sign continues to be debated, particularly because of the prevalence of both seborrheic keratoses and malignancy in the elderly population. Preceding inflammatory skin conditions are known to precipitate eruptions of seborrheic keratoses in otherwise healthy persons. These cutaneous lesions may also be associated with other markers of underlying malignancy such as acanthosis nigricans. We present a young female patient with osteogenic sarcoma in whom eruptive seborrheic keratoses developed. We believe this case is representative of the sign of Leser-Trélat.

Adult↗
PubMed1992

Role of foods in the pathogenesis of chronic paronychia.

BACKGROUND: Chronic paronychia is a condition that is pathologically characterized by spongiotic inflammation; it can be exacerbated by various and concomitant factors. OBJECTIVE: The aim of this study was to assess whether chronic paronychia in food handlers may have clinical, pathologic, and immunohistochemical similarities with immediate contact dermatitis caused by foods. METHODS: Twenty food handlers affected by chronic paronychia were submitted to patch tests with the fresh foods that were suspected of being the cause of the dermatitis. RESULTS: Nine patients had a positive reaction to a 20-minute open patch test with fresh foods applied on the proximal nailfold. In two patients the pathologic study of the positive open patch test site showed acanthosis, exocytosis, and spongiosis of the epidermis and the presence of an inflammatory lymphocytic infiltrate in the dermis. CONCLUSION: Our results confirm the view that an immediate hypersensitivity reaction to foods can be responsible for some cases of chronic paronychia in food handlers.

Adolescent↗
PubMed1993

Juvenile dermatomyositis associated with partial lipoatrophy.

A 26-year-old woman developed partial lipoatrophy 12 years after juvenile dermatomyositis was diagnosed. Renal function was normal, but she had other features typically associated with partial lipoatrophy, including hepatomegaly, acanthosis nigricans, hypertrichosis, and hyperinsulinemia.

Adult↗
PubMed1993

Immunohistochemical features in inflammatory linear verrucous epidermal nevi suggest a distinctive pattern of clonal dysregulation of growth. Military Medical Consortium for the Advancement of Retroviral Research.

BACKGROUND: We studied biopsy material from four patients with inflammatory linear verrucous epidermal nevi (ILVEN) that had a psoriasiform appearance histologically and seven cases of linear epidermal nevi (LEN). Of the seven LEN, five showed hyperkeratosis, papillomatosis, and varying degrees of acanthosis; two had features of epidermolytic hyperkeratosis. Because these lesions have distinctive histologic patterns, we wanted to determine whether we could also demonstrate a distinctive pattern of immunohistochemical markers. METHODS: On all 11 cases we performed immunohistochemical stains for PCNA, factor XIIIa, MAC-387, UCHL-1, and OPD-4. In addition, on one case of ILVEN we performed ICAM-1, ELAM-1, and HLA-DR stains. RESULTS: The pattern of staining of PCNA, factor XIIIa, MAC-387, UCHL-1, and OPD-4 was distinctly different in ILVEN and LEN. Staining for ICAM-1 was present on keratinocytes, and ELAM-1 was present on endothelial cells in two cases of ILVEN. HLA-DR in these same two cases of ILVEN stained mainly dendritic cells in the epidermis. CONCLUSION: The different pattern of staining of PCNA, factor XIIIa, MAC-387, UCHL-1, and OPD-4 in LEN and ILVEN indicates a different mechanism of growth dysregulation. Stains for ICAM-1, ELAM-1, and HLA-DR in ILVEN suggest that an inability to down-regulate the inflammatory infiltrate may be important in the growth dysregulation in ILVEN. In addition, the onset of ILVEN at the time of HIV-1 infection in one patient suggests that HIV-1 infection may be one of many factors that initiates ILVEN in a susceptible person.

Adolescent↗
PubMed1990

Subchronic toxicity of tetrahydrofuran vapors in rats and mice.

Tetrahydrofuran (THF), a four-carbon, cyclic ether, is widely used as an industrial solvent. Groups of 10 rats and mice of each sex were administered THF vapor by whole body inhalation for 13 weeks at exposure concentrations of 0, 66, 200, 600, 1800, and 5000 ppm. The body weights and survival were not affected by THF exposure, except in male mice at 5000 ppm concentration which had reduced weight and three deaths. Clinical signs of central nervous system (CNS) toxicity were observed in both rats and mice at high dose levels. Rats of both sexes exposed to 5000 ppm were ataxic and mice exposed to 1800 or 5000 ppm appeared to be in a state of narcosis. There were no exposure-related gross necropsy findings in rats or mice. At 5000 ppm, decreases in thymic and spleen weights in rats and mice of both sexes and increases in liver weights in both sexes of mice and in female rats were observed. A minimal to mild centrilobular hepatocytomegaly occurred in male and female mice exposed to 5000 ppm THF. Atrophy of the uterus and degeneration of the X zone in the adrenal cortex occurred in female mice exposed to 5000 ppm THF. THF exposure of rats was associated with minimal to mild acanthosis and inflammation in the forestomach. In conclusion, these studies suggest that THF, like other commonly used organic solvents, causes narcosis in rats and mice. Although minimal exposure-related effects were seen in the liver of both species, morphologic changes were present only in mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1990

Toxicity of 4-vinyl-1-cyclohexene diepoxide after 13 weeks of dermal or oral exposure in rats and mice.

4-Vinyl-1-cyclohexene diepoxide (VCHD) is used as a chemical intermediate and as a reactive diluent for diepoxides and epoxy resins. Toxicology studies were conducted by administering VCHD in acetone by dermal application or in corn oil by gavage to F344/N rats and B6C3F1 mice for 13 weeks. In the 13-week dermal studies, groups of 10 rats of each sex received 0.3 ml of VCHD in acetone at concentrations ranging from 6.25 to 200 mg/ml, and mice received 0.1 ml at concentrations ranging from 6.25 to 100 mg/ml. Skin lesions were observed at the site of application at the top two dose levels for both species and sexes, and consisted of acanthosis, parakeratosis, and hyperkeratosis of the epidermis and sebaceous gland hyperplasia. In mice, follicular atrophy of the ovary, characterized by decreased numbers of primary and secondary follicles, occurred at the 50- and 100-mg dose levels. In 13-week oral studies, groups of 10 rats and mice of each sex were administered VCHD at dose levels ranging from 62.5 to 1000 mg/kg in corn oil. In rats and mice, there were body weight decreases in the groups given the two highest doses. The major target organs in rats were forestomach (hyperplasia and hyperkeratosis) and kidney (tubular cell degeneration/necrosis and regeneration). In mice the target organs included forestomach (hyperplasia and hyperkeratosis), ovary (follicular atrophy), and testis (degeneration of germinal epithelium).

Administration, Oral↗
PubMed1983

Interactions of ultraviolet radiation, 12-O-tetradecanoyl-phorbol-13-acetate and retinoic acid in the skin of hairless mice.

Epidermal changes (mitosis, DNA synthesis, hyperplasia and acanthosis) were used to assay the effects of three different treatments on the dorsal skin of hairless mice: ultraviolet radiation (UVR), all-trans retinoic acid (RA) and/or 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Mice receiving 20 exposures to fluorescent sunlamps in 4 wk (200 Robertson-Berger counts, or about one erythema dose daily, 5 days/wk) and subsequent topical application of methanol (3 applications/wk, beginning 3 wk after the end of UVR treatment) still displayed hyperproliferative cellular activity at least 17 wk after the final UV irradiation. Alone, either RA or TPA (0.001% in methanol, applied topically 3 times/wk) had similar hyperproliferative effects on the epidermis initially, but the skin appeared to adapt to continued treatment with TPA after 14 wk while RA-treated skin remained hyperproliferative. To study the effects of each reagent on UVR-exposed skin, an initiation-promotion protocol was used: repeated applications of the test compound were started 3 wk after the end of 4 wk of UVR exposures. By this method, treatment with either TPA or RA resulted in additional epidermal activity initially. However, although TPA-treated epidermis returned to the control level of activity by wk 21, no significant adaptation to RA treatment was seen.

Animals↗
PubMed1991

Studies on the effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on the rodent forestomach.

A novel class of hypocholesterolaemic agents, HMG CoA reductase inhibitors, was shown to cause mucosal thickening in the rodent (mouse and rat) forestomach after subacute/subchronic oral administration. These changes were characterized histologically by acanthosis and hyperkeratosis of the squamous epithelium with submucosal oedema and occasionally cellular infiltration. This drug-induced hyperplastic response was both dose and time dependent, did not occur after subcutaneous administration, and was confined entirely to the rodent forestomach (not observed in any other area of the gastro-intestinal tract). The forestomach hyperplastic response correlated with the pharmacological potency of HMG CoA reductase inhibitors of similar structure (observed to varying degrees with all HMG CoA reductase inhibitors examined to date).

Animals↗
PubMed1994

2-year carcinogenicity study in the male NMRI mouse with 2-ethylhexyl acrylate by epicutaneous administration.

A 2 yr carcinogenicity study of 2-ethylhexyl acrylate (2-EHA) was conducted by applying 25 microliters 21.5, 43 or 85% 2-EHA or 0.015% benzo[a]pyrene (B[a]P) in acetone, three times/wk, to the clipped dorsal skin of male NMRI mice (80 per group). A further group received acetone and served as the vehicle control. After about 7 months of treatment, half of each group was rested from treatment for a period of 2 months, then treated with the promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) for 20 wk followed by observation until termination of the study. The other half of each group received continuous treatment with 2-EHA, B[a]P or acetone, respectively, for 2 yr. Signs signs of skin irritation were apparent in all groups treated with 2-EHA [hyperkeratosis, hyperplasia (acanthosis), crust formation and ulceration]. In the group treated with B[a]P alone or B[a]P with TPA, 79% and 67% of the mice, respectively, bore squamous cell carcinomas. None of the mice treated with acetone or 2-EHA alone developed a skin tumour at the application site. One squamous cell papilloma occurred in each of the groups treated with 2-EHA and TPA, an incidence matched by the single squamous cell papilloma in an untreated area of an acetone control mouse. Thus, 2-EHA proved not to be carcinogenic in the skin of male NMRI mice by epicutaneous administration.

Acrylates↗
PubMed1996

Vulvar vestibulitis subjects undergoing surgical intervention: a descriptive analysis and histopathological correlates.

OBJECTIVE: We describe here a series of selected patients from an established vaginitis research clinic diagnosed with vulvovestibulitis (VV) who underwent surgical intervention for focal disease. Long-term results of surgical correction are reported and characteristic histopathology findings associated with vulvar vestibulitis are emphasized. STUDY DESIGN: A retrospective chart review was carried out to extract relevant clinical, histologic, and outcome data. Tissue blocks of resected specimens were re-examined for specific inflammatory response. RESULTS: Complete data and long-term follow up were available in 16 patients who underwent surgical intervention. All were cared for by the same practitioner (CM). The mean (+/- S.D.) age and gravidity on presentation were 26.9 +/- 5.3 years and 0.9 +/- 1.5, respectively. All but one was caucasian, and 70% were nulliparous. Symptoms included entry dyspareunia (100%), discharge (70%), burning (66%), itching (20%) and other (30%). All patients had focal tenderness; other findings were erythema (50%), acetowhite staining (80%), edema (20%), micropapules (20%) and condyloma (10%). After diagnosis, initial duration of conservative management was 9.4 +/- 6.9 months (1-26 months). No patients received interferon therapy. Because of persistent symptoms the 16 subjects underwent targeted partial perineoplasties. Initial histopathology results revealed chronic inflammation, parakeratosis, hyperkeratosis, edema, koilocytosis and acanthosis. When tissue blocks were cut and stained with Giemsa, large numbers of mast cells were identified. Mean postoperative follow up was 42.0 +/- 22.4 months (10-70 months). Follow up after surgery showed an overall improvement in 15/16 patients (93.8%). CONCLUSIONS: VV affects primarily white, nulliparous women. In the carefully selected subject, surgical intervention has a high success rate, even on long-term follow up. Although the exact etiology for this condition has yet to be elucidated, the presence of mast cells supports an association with other genitourinary inflammatory syndromes such as interstitial cystitis; and allows for speculation about a possible role played by mast cell activation in the etiology of VV.

Adult↗
PubMed1978

Hormone receptors. 7. Characteristics of insulin receptors in a new line of cloned neonatal rat hepatocytes.

1. A new line of cloned, differentiated rat hepatocytes (RL-PR-C) was evaluated for its usefulness as an in vitro system for studying the regulation of the insulin receptor. 2. Insulin rapidly reversibly and specifically bound to RL-PR-C hepatocytes. Binding of tracer 125I-labeled insulin, which was competitively inhibited by native insulin as well as by proinsulin and analogs of insulin and proinsulin in proportion to their biological activity, was not influenced by glucagon, corticotropin, or human growth hormone. Anti-insulin receptor serum from a patient with Acanthosis Nigricans Type B competed with 125I-labeled insulin for binding to cell surface sites. 3. Trypsinization destroyed insulin binding sites, but these were restored by incubation under growth conditions; a 75% restoration of binding sites was achieved by one cell population doubling. 4. RL-PR-C hepatocytes responded to insulin binding by an increase in glycogen synthesis from glucose. The insulin effect was maximal at 85 nM, but was detectable at lower, more physiological, concentrations. 5. Chronic exposure (for at least 3h) of hepatocytes to insulin (10(-10)--(10(-8) M) reduced by up to 60% the number of binding sites for insulin (down-regulation). Down-regulation was prevented by cycloheximide at concentration (10 micron) sufficient to inhibit markedly protein synthesis from tracer isoleucine. Recovery from down-regulation induced by native insulin at 10(-7 M or lower concentrations was complete by 18 h under growth conditions. 6. Although RL-PR-C hepatocytes spontaneously transform after about 90 population doublings, no significant differences between normal and transformed cells were observed in insulin binding characteristics and in interaction of cells with anti-insulin receptor serum. However, transformed cells exhibited a substantially reduced (maximum of 20%) down-regulation response to insulin. 7. RL-PR-C rat hepatocytes appear, for these reasons, to be a useful model system for studying the regulation of the insulin receptor.

Animals↗