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Biomedical subjects

R Tuthill

Publications and source records attributed to R Tuthill.

16 recordsLinked to original sources

An early lesion in hepatic carcinogenesis: loss of heterozygosity in human cirrhotic livers and dysplastic nodules at the 1p36-p34 region.

Loss of heterozygosity (LOH) of chromosome 1 has been suggested, by karyotyping, to be an initial episode in human hepatocarcinogenesis. However, this alteration has not yet been investigated in cirrhotic nodules (CNs) or dysplastic nodules (DNs). In an initial study from explanted or resected cirrhotic livers, LOH in 1p36-p32 was examined in 31 hepatocellular carcinomas (HCCs), 25 low-grade dysplastic nodules (LGDNs), and 24 high-grade dysplastic nodules (HGDNs). In HCCs, LOH was detected most frequently at loci D1S2843 (1p36.1) (28.6%), D1S513 (1p34.3) (29.2%), and MYCL1 (1p34.1) (28.6%). In HGDN and LGDN, LOH incidences at D1S513 were 11.1% and 13.6%, respectively. To further refine those results and to determine sequential relationships among CN, DN, and HCC, LOH was next studied in an additional 53 HCCs, 56 HGDNs, 30 LGDNs, and 215 CNs from 11 explanted human cirrhotic livers, including 30 "nodule-in-nodule" lesions. Seven markers between D1S2843 (1p36.12) and MYCL1 (1p34.1), and 1 each at D1S484 (1q24.1), IGF2R-3 (6q26), and TP53 (17p13.1) were used. LOH at D1S2843 and D1S513 was detected in HCCs (20.4% and 23.5%, respectively), HGDNs (7.7% and 18.5%), LGDNs (13.6% and 6.9%), and CNs surrounding either HCCs or DNs (7.4% and 8.3%). These results demonstrate that LOH at D1S2843 and D1S513 are early events in human liver carcinogenesis. Data from CN surrounding either HCCs or DN, and also nodule-in-nodule lesions, provide evidence supporting a CN-->DN-->HCC progression. Different deletion patterns from multiple HCCs and DNs suggest independent origins for carcinogenesis in the same individual.

Chromosomes, Human, Pair 1↗

Ki-1-positive anaplastic large-cell lymphoma can mimic benign dermatoses.

BACKGROUND: Regressing atypical histiocytosis is a recently described disease characterized by recurrent nodules or ulcers. The cutaneous lesions appear abruptly and then regress only to return in a manner reminiscent of lymphomatoid papulosis. Immunophenotypic analysis has revealed that most cases are a form of anaplastic large-cell Ki-1-positive (CD30+) lymphoma. OBJECTIVE: We describe two patients with Ki-1-positive anaplastic large-cell lymphoma that had clinical and pathologic features of regressing atypical histiocytosis and mimicked benign dermatoses (pyoderma gangrenosum and morphea), causing a delay in confirming the true diagnosis. A third case that was readily recognized as a lymphoma is also presented. METHODS: The clinical and histopathologic findings were recorded. In addition, T-cell receptor gene rearrangement and immunophenotyping were determined in the index case. RESULTS: The index patient and second patient were diagnosed as having Ki-1-positive anaplastic large-cell lymphoma by immunophenotyping and underwent cyclophosphamide, doxorubicin, prednisone, and vincristine (CHOP) chemotherapy with complete remission. The patient detected by chart review died of her disease without receiving antineoplastic therapy; disseminated lymphoma was diagnosed at autopsy. Studies on paraffin-embedded tissue were consistent with Ki-1-positive anaplastic large-cell lymphoma. CONCLUSION: Regressing atypical histiocytosis may clinically resemble some benign dermatoses. Recent evaluation of these cases has shown that many represent a form of Ki-1-positive anaplastic large-cell lymphoma. Multiple skin biopsy specimens with immunophenotyping and gene rearrangement studies are required to arrive at the diagnosis.

Adult↗

Malignant angioendotheliomatosis: an angiotropic lymphoma.

Malignant angioendotheliomatosis is a rare, systemic, usually fatal disease characterized by massive proliferation of large, neoplastic, mononuclear cells within the lumen of small blood vessels. Recent studies suggested that the tumor cells are of lymphoid origin. We studied two cases of malignant angioendotheliomatosis by Southern blot hybridization analysis that showed rearrangements of the immunoglobulin heavy chain and kappa light chain (case 2), indicating the presence of a monoclonal B cell lymphoma. Our results provide further evidence that malignant angioendotheliomatosis is an angiotropic lymphoma.

Aged↗

The gypsy moth caterpillar: a significant new occupational and public health problem.

Seventeen workers in a laboratory where research with the gypsy moth was being performed were subjected to a questionnaire and to skin tests in an attempt to clarify the extent of allergy-like reactions in these workers. Ten of 17 reported dermatologic and/or pulmonary reactions associated with exposure to the caterpillar. Of the subjects with reactions, seven (70%) had reactions to allergens in the past. When all the workers were skin tested with various extracts, there was a strong relationship between reactions to the skin tests and clinical symptoms. The documentation of this problem helps to explain the outbreak of cutaneous reactions seen in the general population during the massive gypsy moth outbreak in spring 1981 in the Northeast.

Adult↗

Abnormal colonic motility in progressive systemic sclerosis.

Progressive systemic sclerosis alters smooth muscle function throughout the gastrointestinal tract. In 10 consecutive patients with the disease, colonic spike activity and contractile activity were measured after a 1000-kcal meal, intramuscular injection of neostigmine, or intravenous injection of metoclopramide. The 1000-kcal meal stimulated a significant increase in spike and contractile activity in normal subjects. Nine of the 10 patients had no increase in motility after eating. Neostigmine or metoclopramide stimulated colonic spike (p less than 0.01) and contractile (p less than 0.02) activity in normal subjects and stimulated colonic motility (p less than 0.01) in four of 10 patients with less severe systemic manifestations of the disease (Group 1). The drugs had no effect on patients with severe progressive systemic sclerosis (Group II). The patients with severe scleroderma had significant gastrointestinal roentgenographic abnormalities and severe cardiac, renal, or pulmonary dysfunction. Four of six Group II patients died from the disease; all four had marked smooth muscle atrophy in the colonic wall. These findings suggest that the gastrocolonic response is absent early in the disease process and that the smooth muscle atrophy occurring with progression of the disease may lead to a more severe colonic motor disturbance.

Adult↗

Specific immunoreactivity of hybridoma-secreted monoclonal anti-melanoma antibodies to cultured cells and freshly derived human cells.

The specificities of monoclonal antibodies against melanoma cells were analyzed using radioimmunoassay, mixed-hemadsorption assay, and quantitative absorption on a variety of malignant and nonmalignant cells. Three of the six hybridoma-secreted antibodies bound to the majority of melanoma cell lines, melanoma tumors, and astrocytoma cell lines as well as to all normal and Epstein-Barr virus-transformed lymphocytes tested. The binding pattern coincides with the presence or absence of the DR antigen on human cells. Conversely, two other antibodies, 19-19 and Nu4B, detected two different antigens common to melanoma and astrocytoma cells only. Cloning of melanoma cells resulted in establishment of DR-positive and DR-negative clones, with the binding of Nu4B antibody retained in all.

Animals↗

Herpes simplex esophagitis: a cause of upper-gastrointestinal bleeding.

Two patients with hemorrhagic esophagitis secondary to esophageal invasion with herpes simplex virus, type 1, are reported. Microscopic examination of the esophageal mucosa revealed multinucleated cells and intranuclear inclusions which are typical of herpes simplex infection. Herpes virus was cultured from each patient. Thus, hemorrhagic esophagitis due to esophageal invasion by herpes simplex virus may be a more frequent cause of upper-gastrointestinal bleeding than previously recognized.

Aged↗

Genetic influence on cadmium-induced hypertension.

Dahl hypertension-resistant (R) and hypertension-sensitive (S) rats were used to determine whether cadmium-induced hypertension is dependent on genetic predisposition. In experiment I, 16 wk-old R and S rats of both sexes were injected with two doses of cadmium (1 and 2 mg/kg body wt, ip), whereas the controls received the same volumes of saline. Hypertension and renal vascular changes were observed in cadmium-injected S rats but not in R rats. The S females appeared more sensitive than S males to the hypertensinogenic effect of cadmium. In experiment II, groups of weanling female R and S rats were given 0, 1, 2.5, 5, or 10 mg cadmium/liter drinking water and fed either a low-salt (0.4% NaCl) or a high-salt (4% NaCl) diet for 28 wk. Cadmium produced cardiac hypertrophy (1 mg cadmium/liter) and hypertension associated with renal vascular changes (1--5 mg cadmium/ liter), and it enhanced proteinuria (1-10 mg cadmium/liter) in S rats on a low-salt diet. Also, the development of salt-induced hypertension was accelerated in cadmium-fed (1 and 2.5 mg/liter) S rats. These adverse effects of cadmium were not detected in R rats on either salt diet. In experiments I and II, cadmium concentrations in the kidneys and liver of S rats were higher (P less than 0.001) than in those of R rats. These data indicate that genetic differences influence the pathogenesis of cadmium-induced hypertension.

Analysis of Variance↗

Role of the gonads in hypertension-prone rats.

In a genetically hypertension-prone (S) strain of rats it was observed previously that males generally developed hypertension more rapidly on a high salt diet than did females although final pressure ultimately were similar in both sexes. A genetic study had shown that there was no sex-linkage involved in setting blood pressure levels, so it was thought that the gonads might be involved. In the present work, castration of males had no effect on blood pressure but in the females it caused a rise in pressure that could not be distinguished from that in males, both on a high and low salt diet. Castration resulted in greater growth in females than in controls, whereas it had the opposite effect in males. It was speculated that these changes were due to influences on pituitary growth hormone with castration increasing the net output of growth hormone (or enhancing receptor sensitivity to it) in the female and the opposite in the male. From the work of others, there are some data compatible with such an interpretation. Experimentally, growth hormone will induce hypertension in rats. Therefore, it is conceivable that growth hormone is involved in the increment in hypertension observed in these castrate females. Because the effect on blood pressure was observed in castrate females on both high and low NaCl diets, it was considered unlikely that the blood pressure effect was simply due to increased NaCl intake in the food associated with greater growth. It was suggested that this rise in blood pressure with cessation of ovarian function might bear on the unsettled question of "menopausal" hypertension in women: in the genetically susceptible individual an increase in growth hormone associated with declining ovarian funtion in the menopause could provide the stimulus for the appearance of hypertension some years earlier than would otherwise have been the case.

Animals↗

Cholangiocarcinoma arising in congenital hepatic fibrosis. A case report.

Congenital hepatic fibrosis (CHF) is a morphologic entity characterized by (1) abnormal fibrous septation, (2) preservation of the basic lobular architecture, and (3) hyperplasia and dilatation of bile ductules. Congenital hepatic fibrosis may present as a cause of portal hypertension in adolescents, in young adults, and, rarely, in older adults. It is this form of the disorder that has been emphasized in the literature. However, CHF may also be seen in association with the infantile polycystic kidney syndrome. In the latter, the hepatic disorder is usually clinically silent. Cholangiocarcinoma is a rare complication of comgenital hepatic fibrosis, with only two previously documented cases reported, to our knowledge. We report a third case and suggest that CHF may represent a dysplastic hamartoma that, with prolonged survival, may eventuate in the development of intrahepatic biliary neoplasia.

Adenoma, Bile Duct↗

Further evidence of the toxicity of NaCl. Increased blood pressure and mortality in the spontaneously hypertensive rat.

The spontaneously hypertensive rat (SHR) of Okamoto and Aoki (4) develops significant hypertension without added dietary salt. Many patients with hypertension have little or no alteration in blood pressure from increments or decrements of salt intake. Such observations have led to a widespread belief that dietary NaCl is important in hypertensives only if blood pressure changes are observed after changes in NaCl intake. Such a simplistic view of hypertension fails to take into account the possibility that morbidity and mortality might be lowered by restricting dietary NaCl, without a concomitant lowering of blood pressure. The effect of a high NaCl intake for periods up to 1 yr has been studied in the SHR with the following conclusions: (a) NaCl accelerated the rate at which hypertension developed in both sexes. (b) The ultimate levels of blood pressure reached by males on either high or low salt diets were similar, however. (c) In females, (1) on high NaCl the average blood pressure ultimately became indistinguishable from males whereas (2) on low NaCl pressure remained significantly lower than that of males. (d) The addition of NaCl to the regimen had a devastating effect on mortality of both sexes and was not directly correlated with the level of blood pressure. Earlier reports were reviewed bearing on the possibility that NaCl is inimical to blood vessels without a necessary relationship to its hypertensinogenic effect. It was concluded that restriction of dietary NaCl would reduce morbidity and mortality in hypertension, whether or not blood pressure was reduced by such measures.

Age Factors↗