Nuclear Enlargement Research Articles

Diagnostic criteria of limited adenocarcinoma of the prostate on needle biopsy

Over a period of 25 weeks 434 needle biopsy specimens of the prostate were sent to the author for consultation because of diagnostic concerns. The final diagnoses were cancer (69%), benign (13%), atypical but not diagnostic (10%), high grade prostatic intraepithelial neoplasia (PIN) (5%), and miscellaneous (3%). The most common benign entities mimicking cancer were atrophy (29 specimens) and adenosis (19 specimens). The 300 cancer specimens were analyzed further. Architecturally, the presence of small glands between larger benign glands was the most common pattern seen in 80% of carcinomas; haphazard growth patterns, single cells, and cribriform glands were seen less frequently. The following diagnostic features were helpful: nuclear enlargement (77% of specimens); prominent nucleoli (76%); pink acellular intraluminal secretions (53%); amphophilic cytoplasm (39%); blue-tinged mucinous secretions (34%); crystalloids (25%); PIN (13%); mitotic figures (11%); and perineural invasion (3%). The mean and median numbers of malignant glands in this series were 31 and 20, respectively (range, two to 300). Tumors with a Gleason score lower than 6 caused greater diagnostic problems for referring physicians because these tumors had a greater number of malignant glands, yet were still sent in for consultation ( P = .0018). Gleason score was positively correlated with prominent nucleoli and amphophilic cytoplasm and inversely correlated with the presence of crystalloids. Prominent nucleoli, which often are quoted as being essential for the diagnosis of prostate cancer, were not seen in 24% of the specimens and seen only rarely in another 25%. The diagnosis of prostate cancer is based on a constellation of features. Even in this series with a limited number of malignant glands, 85% of specimens contained three or more of the above-listed diagnostic features in addition to architectural atypia.

Mycoses of the breast: Diagnosis by fine‐needle aspiration

Fungal infections of the breast are unusual and may clinically mimic carcinoma. When studied by fine-needle aspiration (FNA), such masses may yield necrosis, granulomatous inflammation, reactive histiocytes, and atypical epithelial cells. Cohesive groups of atypical epithelial cells featured nuclear enlargement and overlapping, as well as prominent nucleoli. The organisms may be widely scattered, so that careful evaluation was required for their identification. In concert with provocative clinical findings, these features may lead to an erroneous diagnosis of malignancy. We describe three women with mycotic masses of the breast initially studied by FNA. The first patient presented at age 31 with a large, firm breast mass, chest wall extension, and radiographic evidence of vertebral bone involvement. FNA was requested to confirm the clinical diagnosis of advanced breast carcinoma. In addition to the atypia described above, the smears showed yeast forms indicative of blastomycosis surrounded by neutrophils. She remains well, following antifungal treatment. The second case of Blastomycosis was diagnosed by FNA of a breast mass in a 64-yr-old woman, who also responded to treatment. The third patient's preoperative needle aspiration showed granulomas, but no organisms were identified, even with special stains; silver stains of surgically excised tissue showed histoplasmosis.

Predictors of human papilloma virus in patients with keratinization

Given the prevalence of human papilloma virus (HPV) infection, an attempt was made to determine whether certain factors such as keratinization and/or squamous atypia are associated with its development. Review of our gynecologic cytology files from 1989 yielded 1,615 specimens showing parakeratosis and/or hyperkeratosis, without cytologic evidence of HPV. Concomitant diagnoses included no atypia [keratinization only (KO)], inflammatory squamous atypia (ISA), and squamous atypia (SA). Morphologic follow-up including repeat cytology or biopsy was available for 916 cases, 92 (10.0%) of which possessed changes of HPV. For any case with both cytologic and biopsy evidence of HPV, only the biopsy result was tabulated. HPV on follow-up examination was detected in 52 (6.7%) of the 764 cases with KO; in 20 (20.8%) of the 96 cases with keratinization and ISA (KISA); and in 20 (35.7%) of the 56 cases with keratinization and SA (KSA). The definitive diagnosis of HPV was based on previously described features (Gupta, In: Comprehensive Cytopathology, Philadelphia: WB Saunders, 1991:133-140) including nuclear enlargement with nuclear membrane irregularities in combination with sharply demarcated paranuclear cytoplasmic clearing. Affected cells have rounded borders. Binucleated cells are not uncommon. The increasing percentage of HPV from KO to KISA to KSA is not necessarily surprising. However, mathematical analysis revealed statistically significant differences in the development of HPV in each of the 3 groups: KISA vs. KO (P < 0.001), KSA vs. KO (P < 0.001), and KSA vs. KISA (P < 0.05). Therefore, a cytologic diagnosis of keratinization with ISA or especially SA should warrant closer follow-up than that of KO.

Dose dependence of diethylnitrosamine-induced nuclear enlargement in embryonal turkey liver.

Avian embryos (turkey) were exposed to diethylnitrosamine in ovo. On the first day of incubation doses of 0.5-5.0 mg/egg were injected into the white of the fertilized egg. The experiment was terminated 4 days before hatching. Livers were removed and prepared for subsequent histological examination. In haematoxylin and eosin stained sections the areas of hepatocyte nuclear profiles were measured by semi-automatic image analysis. In liver samples of diethylnitrosamine-exposed embryos hepatocyte nuclei of more than twice the size of normal hepatocyte nuclei were found. The incidence of the enlarged nuclei was clearly dose dependent. An increase in the size of hepatocyte nuclei was observed after low doses of diethylnitrosamine that did not induce common signs of non-specific toxic effects, e.g. cell death, fat vacuoles or loss of glycogen. The slope of the dose-response curve was rather steep. A 10-fold increase in the dose of the carcinogen resulted in a 100-fold increase in the incidence of enlarged hepatocyte nuclei. In combination with preneoplastic foci of altered hepatocytes, the quantification of nuclear enlargement can provide a valuable complementary parameter for the evaluation of carcinogen-induced effects in ovo.

Investigations into the mechanisms of carcinogen-induced nuclear enlargement in HeLa S3 cells in vitro

Carcinogen-induced nuclear enlargement has been reported both in vitro and in vivo, but the mechanism, and whether it is causally related to carcinogenesis, has not yet been established. This study was designed to investigate the role of increased DNA content, such as might occur in polyploidy, in induction of nuclear enlargement. The effects of two genotoxic carcinogens, N-methyl- N-nitrosourea and adriamycin, were compared with the effects induced by diethylstilboestrol, which is arguably a non-genotoxic carcinogen but is known to induce polyploidy. HeLa S3 cells were used as the model system for comparison with previous studies. N-methyl- N-nitrosourea and adriamycin both induced a concentration-related increase in nuclear size 24 to 72 hr after a 30 min pulse-treatment. This was accompanied by an increase in the proportions of cells in the G 2 + M stage of the cell cycle, possibly due to a G 2 block. There was some evidence of polyploidy with adriamycin but not with N-methyl- N-nitrosourea. The distributions of nuclear areas indicated that increases in ploidy contributed to, but did not totally account for, the nuclear enlargement. In contrast, diethylstilboestrol increased the range of nuclear areas and DNA content, to both less than and greater than that of control cells, but only after a prolonged exposure period of 48 hr. These data were consistent with diethylstilboestrol inducing spindle damage. These results demonstrate that carcinogen-induced nuclear enlargement is only partially explained by increased nuclear DNA content, and that certain classes of non-genotoxic carcinogen may produce a completely different pattern to that from genotoxic carcinogens.

C-erbB-2 Oncogene Expression in Prostatic Intraepithelial Neoplasia: Mounting Evidence for a Precursor Role

The search for the precursor of invasive prostatic adenocarcinoma has intensified in recent years, focusing on the spectrum of histopathologic changes referred to as high-grade prostatic intraepithelial neoplasia. This microscopic finding, considered to be the most likely precursor of invasive carcinoma (7), is characterized by cellular proliferations within pre-existing ducts and glands, with cytologic changes mimicking cancer, including nuclear and nucleolar enlargement. Prostatic intraepithelial neoplasia coexists with cancer in more than 85% of cases but retains an intact or fragmented basal cell layer, unlike cancer that lacks a basal cell layer (2). The clinical importance of recognizing prostatic intraepithelial neoplasia is based on its strong association with prostatic carcinoma. Prostatic intraepithelial neoplasia has a high predictive value as a marker for adenocarcinoma, and its identification in biopsy specimens of the prostate warrants further search for concurrent invasive carcinoma. Studies, to date, have not determined whether prostatic intraepithelial neoplasia remains stable, regresses, or progresses, although the implication is that it can progress (2). The identification of specific and consistent molecular changes in prostatic intraepithelial neoplasia, such as pl60 erbB3 and pl85erbB~2 overexpression, adds further support to the expanding body of evidence indicating the premalignant nature of this lesion.

Fine-needle aspiration of Hürthle cell lesions. A cytomorphologic approach to diagnosis.

Hürthle cells may be found in fine-needle aspirates of the thyroid (FNATs) from Hürthle cell tumors (HCTs) and nonneoplastic Hürthle cell lesions, including Hashimoto's thyroiditis and goiter. To differentiate the characteristic cytomorphologic features from these lesions, the authors studied 38 surgically excised Hürthle cell lesions of the thyroid. Preoperative FNATs were reviewed for a number of architectural and cytologic features. The chi-squared and Fisher's exact tests were used for statistical analysis. There were many statistically significant cytologic differences between HCTs and nonneoplastic Hürthle cell lesions. Statistically significant features indicating an HCT versus nonneoplastic Hürthle cell lesion included the following: a high percentage (> 90%) of Hürthle cells, single Hürthle cells (> 10%), cellular dyshesion, large nucleoli, significant nuclear pleomorphism, significant nuclear enlargement, absence of macrophages, absence of plasma cells, and absence of or few lymphocytes. The architecture of cell groups, cellularity, amount of colloid, and multinucleation appeared to be of no value. The presence of a high percentage of dyshesive Hürthle cells with large nucleoli, with some cells showing significant nuclear enlargement and pleomorphism, associated with a lack of lymphoplasmacytic inflammatory cells, appears statistically predictive of an HCT and should enable the differentiation of an HCT from a nonneoplastic Hürthle cell lesion.

Effects of Monocrotaline Pyrrole on Cultured Rat Pulmonary Endothelium

Administration of monocrotaline pyrrole (MCTP), a putative toxic metabolite of the pyrrolizidine alkaloid, monocrotaline (MCT), results in delayed and progressive pneumotoxicity in the rat. It has been suggested that the lung injury caused by this compound may be initiated by an interaction between MCTP and cells of the pulmonary vasculature. A likely site for initial binding of this reactive electrophile is the pulmonary endothelium. MCTP causes direct toxicity to cultured bovine and porcine pulmonary artery endothelial cells (BECs and PECs, respectively), but there exist species differences both in whole-animal response to the parent alkaloid and in cellular response to direct application of MCTP. In this study, the changes in cultured rat pulmonary vascular endothelial cells (RECs) after a single administration of MCTP were characterized in order to compare these with changes previously identified in this species in vivo. Studies with RECs have also provided an additional model for examination of species-related differences in response to this toxicant. MCTP caused a delayed and progressive release of lactate dehydrogenase from REC monolayers. Progressive cell detachment was evident and remaining cells became enlarged, with morphologic changes comparable to those reported previously in BECs, including cytoplasmic vacuolization and nuclear enlargement. MCTP inhibited cell proliferation at concentrations of 0.05 μg MCTP/ml or greater, and DNA crosslinking was evident at 24 and 48 hr post-treatment. These results suggest that MCTP is directly toxic to cultured RECs, and the development of changes is reminiscent of that seen in the rat in vivo. The cytostatic nature of the compound, in combination with its cytolytic effect on RECs, could contribute to the development of pulmonary edema and other lung vascular changes seen in rats treated with MCT or MCTP.

Toxicity and Carcinogenicity of Chronic Exposure to Tris(2-chloroethyl)phosphate

Toxicity and Carcinogenicity of Chronic Exposure to Tris(2-chloroethyl)phosphate. Matthews, H. B., Eustis, S. L., and Haseman, J. (1993). Fundam. Appl. Toxicol. 20, 477-485.Previous short-term studies of tris(2-chloroethyl)phosphate (TRCP), a flame retardant used in industrial and consumer products, demonstrated that repeated administration of 350 mg TRCP/kg body wt by oral gavage resulted in necrosis of pyramidal neurons in the CA1 region of the hippocampus of F344 rats, but not in B6C3F1 mice. The 2-year studies reported here were designed to characterize the chronic toxicity and potential carcinogenicity of TRCP in each sex of F344 rats and B6C3F1 mice. Groups of 60 rats per sex received 0, 44, or 88 mg/kg by oral gavage, once per day, 5 days per week, for up to 103 weeks. Groups of 60 mice per sex received 0, 175, or 350 mg/kg by oral gavage on the same dosing schedule. Each of these groups contained 10 animals which were euthanized at 66 weeks. The principal toxic effects of chronic exposure of rats to TRCP occurred in the brain and kidney. In contrast to the findings in the 16-week studies, a hippocampal lesion was not observed in the brain, although degenerative lesions were widely distributed in the gray and white matter of the brain stem and cerebral cortex of high-dose female and, to a lesser extent, male rats. These findings suggest that the hippocampal necrosis may be dependent upon the size of the individual doses or may have a pathogenesis different from that of the lesions in the brain stem and cerebral cortex. The other primary effect of chronic exposure was a dose-dependent increased incidence of renal tubule hyperplasia and adenoma. Renal tubule neoplasms, primarily adenomas, were observed in 4% of control, 10% of low-dose, and 50% of high-dose male rats and in 0% of control, 4% of low-dose, and 10% of high-dose female rats. There were also marginal increases in mononuclear cell leukemia and in thyroid follicular neoplasms in dosed male and female rats that were not clearly related to TRCP administration. Mice were less sensitive to TRCP than rats and lesions attributable to chemical administration in mice were limited to a dose-dependent increased incidence of karyomegaly (nuclear enlargement) in epithelial cells of proximal tubules in the inner cortex and outer stripe of the outer medulla of the kidneys both sexes. Marginal increases in the incidence of renal tubule neoplasms in male mice and harderian gland neoplasms in female mice were not considered clearly related to TRCP administration.

Toxicity and Carcinogenicity of Chronic Exposure to Tris(2-chloroethyl)phosphate

Previous short-term studies of tris(2-chloroethyl)phosphate (TRCP), a flame retardant used in industrial and consumer products, demonstrated that repeated administration of 350 mg TRCP/kg body wt by oral gavage resulted in necrosis of pyramidal neurons in the CA1 region of the hippocampus of F344 rats, but not in B6C3F1 mice. The 2-year studies reported here were designed to characterize the chronic toxicity and potential carcinogenicity of TRCP in each sex of F344 rats and B6C3F1 mice. Groups of 60 rats per sex received 0, 44, or 88 mg/kg by oral gavage, once per day, 5 days per week, for up to 103 weeks. Groups of 60 mice per sex received 0, 175, or 350 mg/kg by oral gavage on the same dosing schedule. Each of these groups contained 10 animals which were euthanized at 66 weeks. The principal toxic effects of chronic exposure of rats to TRCP occurred in the brain and kidney. In contrast to the findings in the 16-week studies, a hippocampal lesion was not observed in the brain, although degenerative lesions were widely distributed in the gray and white matter of the brain stem and cerebral cortex of high-dose female and, to a lesser extent, male rats. These findings suggest that the hippocampal necrosis may be dependent upon the size of the individual doses or may have a pathogenesis different from that of the lesions in the brain stem and cerebral cortex. The other primary effect of chronic exposure was a dose-dependent increased incidence of renal tubule hyperplasia and adenoma. Renal tubule neoplasms, primarily adenomas, were observed in 4% of control, 10% of low-dose, and 50% of high-dose male rats and in 0% of control, 4% of low-dose, and 10% of high-dose female rats. There were also marginal increases in mononuclear cell leukemia and in thyroid follicular neoplasms in dosed male and female rats that were not clearly related to TRCP administration. Mice were less sensitive to TRCP than rats and lesions attributable to chemical administration in mice were limited to a dose-dependent increased incidence of karyomegaly (nuclear enlargement) in epithelial cells of proximal tubules in the inner cortex and outer stripe of the outer medulla of the kidneys both sexes. Marginal increases in the incidence of renal tubule neoplasms in male mice and harderian gland neoplasms in female mice were not considered clearly related to TRCP administration.

Mitochondrial enlargement and basement membrane thickening of renal proximal tubules, possible initiators of microalbuminuria in non-insulin-dependent diabetics (NIDDM).

To clarify the morphological changes in renal proximal tubules at the onset of diabetic nephropathy, we observed 177 biopsy samples from patients with Non-Insulin-Dependent Diabetics (NIDDM) using light and electron microscopy. Group I had no proteinuria (p.u.), group II had p.u. < or = 0.5 g/day, group III had p.u. > 0.5 g/day, group IV had serum creatine level (Cr) > 1.5 mg/dl. Twenty age-matched normal patients and 80 patients with IgA nephropathy were used as controls. In groups I and II, the following features were significantly different from those in the controls: spherical enlargement of mitochondria (MT) in proximal tubule cells, hypertrophy of proximal tubule cells and their nuclei, and thickening of both the proximal tubule basement membrane (TBM) and the glomerular basement membrane (GBM). Among the histological changes observed in group I, the thickness of the GBM and TBM indicated that the disease would lead to diabetic nephropathy. MT enlargement was positively correlated with nuclear and cytoplasmic enlargement of the proximal tubule cells in diabetic patients (p < 0.05), but was not correlated with other morphological changes or disease prognosis. Glomerular nodular lesions, glomerular sclerotic change, and cortical tubulointerstitial fibrosis became evident in groups III and IV. From the above, we concluded that MT enlargement and thickening of the TBM are possible causes of reduced active transport in the proximal tubules, causing microalbuminuria in diabetics, and initial impairment of post-tubule transport.

Superficial nuclear enlargement without koilocytosis as an expression of human papillomavirus infection of the uterine cervix: an in situ hybridization study.

Nuclear enlargement of the superficial cervical epithelial cells in the absence of koilocytosis is frequently observed. The purpose of this study was to investigate whether this change represents human papillomavirus (HPV) infection. We reviewed 257 cervical biopsies with the diagnosis of "suggestive of condyloma," mild or moderate dysplasia, or both. Of the 257 consecutive biopsies, 23 fulfilled the two criteria: the superficial cells had a nuclear diameter of at least twice that of the basal nuclei, and complete absence of koilocytosis was seen. Parallel sections from each paraffin block were hybridized with biotinylated probes for HPV 6/11, 16/18, and 31/35/51 under high-stringency conditions. The cases that were negative at high-stringency conditions were then hybridized under low-stringency conditions with a mixture of the three HPV probes. Twelve of the 23 cases (52.17%) were positive for HPV, including one positive for HPV 16/18 in one area and for HPV 31/35/51 in another area, four positive for HPV 31/35/51, two positive for HPV 16/18, two positive for HPV 6/11, and three positive for HPV probe mixture at low-stringency conditions. The positive in situ hybridization was located predominantly in the enlarged nuclei in the superficial layers. In conclusion, HPV infection can be expressed as nuclear enlargement in the superficial layers of the cervical epithelium in the absence of koilocytosis.

Oral contraceptive-associated liver cell adenoma and hepatocellular carcinoma. Cytomorphology and mechanism of malignant transformation

From January 1976 to May 1990, 1673 patients with a liver mass or masses detected by imaging techniques underwent percutaneous fine-needle aspiration biopsy of the liver. Of these, 99 were diagnosed cytologically as "hepatocellular carcinoma" and 9 as "consistent with liver cell adenoma." The cytologic diagnoses were confirmed in the follow-up of all cases. Among the 99 patients with hepatocellular carcinoma, 3 had taken oral contraceptives for a period of 10, 11, and 12 years, respectively. The nine patients with liver cell adenoma were all users of oral contraceptives over a period ranging from 5 to 10 years. Of these, two who had taken oral contraceptives for a period of 8 and 10 years, respectively, had foci or areas of liver cell dysplasia within the adenomas. The cytologic criteria for the diagnosis of liver cell dysplasia included cytoplasmic and nuclear enlargement, nuclear pleomorphism together with prominent nucleoli, hyperchromasia and multinucleation. The cytologic features of liver cell dysplasia strikingly mimic hepatocellular carcinoma. From this study, the foci or areas of liver cell dysplasia arising within the liver cell adenomas appear to be the missing link responsible for the transformation of liver cell adenoma to carcinoma. It is believed that liver cell adenomas are not premalignant and may undergo reversible change after withdrawal of causative agents, whereas liver cell dysplasia is an irreversible, premalignant change and will eventually progress to hepatocellular carcinoma.

Computerised Image Analysis of Nuclear Enlargement Assay in HeLa Cells

It has been observed that cells often respond to carcinogens by nuclear enlargement. For this reason, new morphometric approaches have been developed to evaluate cell modifications in pre-carcinogenesis assays. Morphometric computerised automatic analysis, with original software, was performed on HeLa cells treated with various compounds (hydroxyurea, dimethylnitrosamine, N-methyl- N’-nitro-nitrosoguanidine and cyclophosphamide) to evaluate nuclear size changes.

Carcinogen-induced nuclear enlargement in cultures of rat tracheal primary epithelial cells

Rat tracheal epithelial cells were cultured for 72 hr and then exposed for 3 hr to a range of test chemicals, including non-carcinogens, and direct-acting and activation-dependent carcinogens. The cells were then washed and cultured in fresh medium without the test chemicals for a further 24, 72 or 120 hr. Nuclear size measurements were then made. At 72 and 120 hr after exposure, those cultures treated with the non-carcinogens pyrene and anthracene had distributions of nuclear area similar to those of the solvent controls. All cultures treated with activation dependent carcinogens ( N-nitrosopyrrolidine, N-nitrosodimethylamine, benzo[ a]pyrene, dimethylbenz[ a]anthracene or 4-nitroquinoline- N-oxide) or direct-acting carcinogens (nitrogen mustard or methylmethanesulphonate) showed a shift in distributions to the right, indicating enlarged nuclei. These results indicate that carcinogen-induced nuclear enlargement can occur in cultures of rat primary tracheal epithelial cells, and that this may be a useful indicator system for respiratory carcinogens.

Computerized image analysis of nuclear enlargement in HeLa cells treated with pre- and proximate carcinogens

Computerized image analysis of nuclear enlargement in HeLa cells treated with pre- and proximate carcinogens

Cytologic Correlates of Cervical Papillomavirus Infection

A fundamental question in Papanicolaou smear screening is the specificity of cytologic criteria for the recognition of genital human papillomavirus (HPV) infection. To address this problem, we conducted a two-phase study of routinely screened women to determine the efficiency with which cytologic findings identified the presence of HPV DNA, focusing on the criteria for identifying smears as "atypical." In phase 1, 25 of 290 (8.6%) smears were designated atypical, but only 3 (12%) of the samples contained HPV nucleic acids. Four of five (80%) smears designated as diagnostic of HPV/cervical HPV infection were associated with HPV nucleic acids. By applying more stringent criteria for the diagnosis of atypical in phase 2, only 3 of 166 (1.8%) were identified as atypical. Of these, two (67%) contained HPV nucleic acids. The criteria that most efficiently correlated with HPV nucleic acids included prominent nuclear enlargement with either multiple nuclei or nuclear hyperchromatism. On review of the 19 HPV-positive and 20 control HPV-negative smears originally diagnosed as cytologically negative, the above criteria identified an additional 3 cytologically atypical/positive smears versus none (0 of 20) in the control group. This study supports the concept that cytologic abnormalities suggesting "subtle" HPV infection may be extremely difficult to distinguish from non-HPV-related changes, and that criteria used to imply "suggestive but not diagnostic for HPV infection" should be continually reevaluated. The potential role of HPV DNA analysis in Papanicolaou smear interpretation is discussed.

Effects of advancing age on the central response of rat facial neurons to axotomy: Light microscope morphometry

Following axotomy, the regrowth of peripheral axons takes longer in older individuals than in young ones. The present study compares central responses of facial motor neurons to a crush injury of the facial nerve in 3-month-old and 15-month-old male rats sampled through 28 days post-crush (dpc). Neuronal somata, nuclei, and nucleoli were measured in 30 microns brain stem sections within subdivisions of the facial nucleus that contain the cell bodies responsible for the movement of the vibrissae. The temporal patterns of change in the size of the three structures were interpreted with reference to the re-establishment of functional connections, i.e., the return of voluntary vibrissae activity, which is delayed by 4 days in the older animals relative to the younger ones. There was no age-related difference in the pattern of somal swelling and recovery, nor was there an age-related difference in the response of nuclei and nucleoli to axotomy through 4 dpc. Both nuclei and nucleoli increased in size in animals of both age groups, but after 4 dpc in the older animals nuclear enlargement was prolonged and the nucleolar increases were less robust compared to the younger animals. The greatest age difference appeared with the re-establishment of functional connections. In the 3-month-old animals, the resumption of whisker activity coincided with vigorous transient increases in the sizes of nuclei and nucleoli; in the 15-month-old animals, there was little nuclear response to functional recovery and a comparatively small increase in nuclear sizes.(ABSTRACT TRUNCATED AT 250 WORDS)

Histopathologic Spectrum of Clinically Atypical Melanocytic Nevi

We studied the clinically most atypical pigmented lesion removed from each of 142 patients with newly diagnosed sporadic melanoma. The specimens were categorized as to the type of nevus, ie, junctional or compound, presence of congenital features, and degree of nuclear atypicality--presence of nuclear enlargement, nuclear pleomorphism, hyperchromatism, and prominent nucleoli--of intraepidermal nevomelanocytes. The frequency of nuclear abnormality was graded as 1 (rare cells), 2 (10% to 50% of cells), or 3 (greater than 50% of cells) for each nuclear parameter. Among all lesions, 42 (29.6%) were junctional nevi, 74 (52.1%) were compound nevi, and 14 (9.9%) were dermal nevi. Eighteen percent of the total were either dysplastic nevi (23 cases) or malignant melanoma in situ (three cases). Fourteen nevi (9.9%) had congenital features. There were 12 junctional and 39 compound nevi and one dermal nevus that exhibited nuclear abnormality, but only four junctional nevi compared with 19 compound nevi had sufficient atypia for a designation of dysplastic nevus. Only two nevi with congenital features demonstrated any nuclear abnormality, and these were clearly nondysplastic. Thus, among nevi surgically removed as the clinically most atypical lesion in this study, compound nevi were much more likely to demonstrate nuclear atypia (and dysplasia) than were other nevi, ie, junctional or dermal nevi, or nevi with congenital features.

Smooth muscle growth in the mature rat: role of sympathetic innervation

The role of sympathetic innervation in maintaining smooth muscle structure and function was investigated in the mature rat. Superior tarsal muscle volume, smooth muscle cell nuclear size and packing density, and α-adrenoceptor-mediated contractions were assessed in Sprague-Dawley rats at 3 months of age, and in rats at 6 months of age in which one muscle had intact sympathetic innervation and the contralateral mate was sympathectomized at 3 months. Body weight was stable between 3 and 6 months. In contrast, both maximum contraction and muscle volume increased by more than 50% in the innervated organ, while chronic sympathectomy prevented these increases. Both nuclear packing density and nuclear size increased with age. The greater packing density was abolished by sympathectomy, but nuclear enlargement was not. Adrenoceptor supersensitivity was not observed, although the agonist dose producing 50% maximum contraction varied as a function of contractile capacity. It is concluded that superior tarsal smooth muscle growth continues independently of changes in body weight in the mature rat. Structural and functional deficits observed following chronic sympathetic denervation of this muscle are attributable to prevention of growth rather than regressions in size and contractile capacity.