PubMed Health⌕ Search

Biomedical subjects

J V Frei

Publications and source records attributed to J V Frei.

At least 19 recordsLinked to original sources
PubMed1992

Hereditary nonpolyposis colorectal cancer (Lynch syndrome II). Diploid malignancies with prolonged survival.

DNA flow cytometry was performed on 44 paraffin blocks from 16 specimens of 11 lesions in five patients from two families identified as probably having the dominant gene of the Lynch Type II syndrome. All but one specimen showed diploidy, although two such specimens were metastases and one a recurrence. The one aneuploid gastric biopsy was followed by a resection with diploidy in all 13 blocks from the malignancy and may represent a superficial change without clinical significance. The prolonged survival after discovery of malignancy in such families may be explained in part by diploidy of the lesions.

Adult↗
PubMed1992

Aneuploidy in nonneoplastic and benign melanocytic and breast lesions determined by DNA flow cytometry.

A total of ten of 60 nonneoplastic lesions and eight of 76 benign neoplasms of skin and breast showed an aneuploid peak in DNA flow cytometry profiles obtained from archival paraffin blocks. This confirms previous similar scattered reports and emphasizes that caution needs to be exercised in interpreting aneuploidy in DNA flow cytometry to mean preneoplasia, neoplasia, or malignancy.

Aneuploidy↗
PubMed1991

Transplantation of a donor liver with haemochromatosis: evidence against an inherited intrahepatic defect.

An iron loaded liver from a 40 year old man with occult haemochromatosis was transplanted into a 19 year old woman with acute liver failure secondary to a paracetamol overdose. Increased parenchymal hepatic iron was found in a liver specimen at biopsy undertaken because of mild rejection 30 days after transplantation. After transplantation the patient had two episodes of liver rejection confirmed by biopsy. The hepatic iron concentration fell from 161 mumol/g on day 30 after transplant to 26.5 mumol/g (normal less than 40) on day 210. Iron absorption, measured 45 days after transplant, was in the normal range at 12.4%. The rapid fall in hepatic iron and the normal iron absorption study result suggest that the genetic defect of haemochromatosis is not exclusively an intrahepatic defect.

Adult↗
PubMed1991

DNA flow cytometry of large-bowel biopsies showing that adenoma tissue predicts the ultimate nature of the lesions.

Ploidy of neoplastic large-bowel cells in lesions from which biopsies showed only adenoma tissue by histopathologic examination was investigated retrospectively by DNA flow cytometry. Biopsy and resected-specimen blocks gave interpretable ploidy profiles from 83 lesions. The expectation that adenomas will show diploidy in biopsies and that adenocarcinomas will show aneuploidy in biopsies was fulfilled in 80% of the lesions. In addition, four lesions with diploid biopsies were polyps with minimal invasion. Thus, diploidy would have correctly predicted that local resection was adequate treatment for 62 lesions and conversely that cancer resection was the appropriate treatment for 8 lesions, for an overall predictive success rate of 87%. In conjunction with endoscopic, radiologic and other data, DNA flow cytometry of biopsies from apparently benign large-bowel lesions could become a useful addition to therapeutic decision-making.

Adenocarcinoma↗
PubMed1991

Granulomatous hepatitis and fever of unknown origin. An 11-year experience of 23 cases with three years' follow-up.

Granulomatous hepatitis is a common cause of fever of unknown origin in up to 13% of patients with prolonged fever. Attempts to define an exact etiology of the granulomatous hepatitis frequently does not yield a precise diagnosis, so that the physician must consider empiric treatment. In this paper we retrospectively review 23 patients in whom granulomatous hepatitis was found as part of the initial assessment of fever of unknown origin, and we report on their outcomes after an overall prospective follow-up of 37 months. In 26% a precise diagnosis was established at the time of assessment: Q-fever in three, mycobacterial disease in two, and histoplasmosis in one. In the remaining 74% no etiology was established after 44 months follow-up. Forty-one percent of the idiopathic group resolved spontaneously without therapy, and 18% received short-term prednisone or indomethacin with a favourable outcome. The remaining 41% required long-term prednisone therapy for a mean of 33.1 months, but all have remained afebrile and otherwise healthy after 59.6 months follow-up. We conclude that patients with fever of unknown origin who are diagnosed as having idiopathic granulomatous hepatitis have an excellent prognosis, even the minority who require long-term corticosteroids.

Adult↗
PubMed1991

Hepatic zinc in hemochromatosis.

Since an intestinal absorptive interaction between iron and zinc has been described in animals and humans, the possibility of increased accumulation of zinc as well as iron in the liver was studied in patients with hereditary hemochromatosis. Hepatic zinc was determined by atomic absorption spectrophotometry in liver biopsy specimens from 21 homozygotes for hemochromatosis, 21 normal liver samples from autopsies, and 15 cases of cirrhosis unrelated to iron overload. Mean hepatic zinc concentrations in the three groups were compared by one-way analysis of variance. Hemochromatosis patients had hepatic iron determinations by atomic absorption spectrophotometry, and iron absorption studies using 59Fe and total body counting had been previously documented in 18 of the 21 hemochromatosis patients. The mean hepatic zinc was significantly increased at 25.9 +/- 26.7 mumol/g (dry weight) in the hemochromatosis patients, as compared to 4.99 +/- 1.51 mumol/g in the control patients (p less than 0.05), and 2.13 +/- 1.13 mumol/g in the cirrhosis patients without iron overload (p less than 0.05). Hepatic zinc concentration was elevated in hemochromatosis patients who had either normal histology, fibrosis, and cirrhosis. Hepatic zinc concentration was not directly related to patient age, hepatic iron concentration, or iron absorption. In conclusion, hepatic zinc was increased approximately fivefold in patients with hemochromatosis. This finding suggests the concomitant hepatic accumulation of zinc as well as iron in this disorder, possibly by means of increased intestinal absorption of zinc and hepatic sequestration.

Adult↗
PubMed1990

Stable genes.

Some genes such as those for histones and RNAs are conserved unchanged through much of evolution and have numerous tandem repeat copies in the genome. It is proposed that as yet undetected 'polystrand' enzymes use such multiple copies as a means of conserving their sequence by comparing the copies and eliminating errors.

Animals↗
PubMed1990

Hepatic iron and iron absorption in hemochromatosis.

The relationship between iron absorption and hepatic iron was studied in 21 patients with hemochromatosis. Iron absorption was studied using 59Fe and total body counting and hepatic iron was measured by atomic absorption spectrophotometry. Iron absorption was inversely related to hepatic iron concentration (r = -0.51, p = 0.009) in this patient population. This observation suggests that iron absorption is regulated by body iron stores even in hemochromatosis, and does not support the hypothesis that the primary metabolic defect in hemochromatosis is a deregulation of iron absorption in relation to iron stores.

Absorption↗
PubMed1989

Multiple focal nodular hyperplasia of the liver associated with vascular malformations of various organs and neoplasia of the brain: a new syndrome.

Focal nodular hyperplasia (FNH) is a lesion of the liver in which a large anomalous artery is located within a region of hyperplastic hepatic parenchyma. Patients with FNH commonly have other lesions, often vascular in nature, in the liver or other organs. We have noted that these associated lesions almost always occur in patients with multiple FNH. We therefore studied 27 autopsied patients with FNH. All 13 with multiple FNH had other lesions such as hemangioma of liver, meningioma, astrocytoma, telangiectasis of the brain, berry aneurysm, dysplastic systemic arteries, and portal vein atresia. One patient had several of these lesions including multiple FNH, meningioma, astrocytoma, vascular malformation of the brain stem, and hemangioma of the liver. In contrast, among the 14 patients with solitary FNH there were no associated lesions, except for hepatic hemangioma in one patient. The prevalence of this syndrome was estimated by examination of 2500 serial autopsies and autopsies with various components of the syndrome. On review of 73 consecutive autopsies with meningioma, three had multiple FNH, compared with seven of 2500 consecutive adult autopsies (P less than 0.001). Multiple FNH was found in two of 83 autopsies with astrocytoma (P less than 0.05) and in one of 139 autopsies with berry aneurysm (not significant). We describe a telangiectatic subtype of FNH which occurs in this syndrome as well as in a minority of patients with solitary FNH. The existence and character of this syndrome suggest that there may be an underlying systemic abnormality in some patients having components of the syndrome. Investigation of patients with multiple FNH lesions may reveal significant treatable lesions.

Adolescent↗
PubMed1979

Synthesis of 1-(2-hydroxyethyl)-1-nitrosourea and comparison of its carcinogenicity with that of 1-ethyl-1-nitrosourea.

1-(2-Hydroxyethyl)-1-nitrosourea (HNU) was prepared by the action of nitrosyl chloride on (2-hydroxyethyl)urea. Attempts to synthesize HNU by an earlier described method were unsuccessful and led to the formation of the cyclized derivative 1-nitroso-2-oxazolidone. In addition, the spectral data that we obtained for HNU differed from those reported earlier. Female C57BL/Cbl mice were treated with single ip doses of HNU to determine its median lethal dose (LD50) and its ability to induce lymphocytic thymic lymphomas in these mice. The results showed that the LD50 was the same as that for 1-ethyl-1-nitrosourea (ENU) and that its was slightly more potent than ENU as a carcinogen in this system.

Animals↗
PubMed1978

Alkylation of deoxyribonucleic acid in vivo in various organs of C57BL mice by the carcinogens N-methyl-N-nitrosourea, N-ethyl-N-nitrosourea and ethyl methanesulphonate in relation to induction of thymic lymphoma. Some applications of high-pressure liquid chromatography.

1. Methods were developed for analysis of alkylpurines, O2-alkylcytosines, and representative phosphotriesters [alkyl derivatives of thymidylyl(3'-5')thymidine], in DNA alkylated in vivo, using high-pressure liquid chromatography. 2. The patterns of alkylation products in DNA in vivo at short times were closely similar to those found for reactions in vitro. Alkylation by the nitrosoureas was complete in vivo within 1 h, but with ethyl methanesulphonate was maximal at 2--4h. 3. The time course of persistence of alkylation products in vivo was determined for several tissues. In addition to the rapid loss of 3- and 7-alkyladenines reported previously for all tissues, a relatively rapid loss of O6-alkylguanines from DNA of liver was found which was more rapid at lower doses. In brain, lung and kidney, excision of O6-alkylguanine was much less marked, but was not entirely excluded by the data. In thymus, bone marrow and small bowel, all alkylated bases were lost with half-lives of 12--24h, at non-cytotoxic doses of alkylation. 4. No evidence for any marked excision of other minor products from alkylated DNA in vivo was found; thus 1-methyladenine, O2-ethylcytosine (found in appreciable amount only with N-ethyl-N-nitrosourea), 3-methylguanine, and dTp(Alk)dT persisted in alkylated DNA, including DNA of liver. 5. The induction of thymic lymphoma was determined over the range of single doses by intraperitoneal injection up to about 60% of the LD50 values, and related to the extent of alkylation of target tissues thymus and bone marrow. With N-methyl-N-nitrosourea over 90% tumour yield was attained at 60 mg/kg, and with N-ethyl-N-nitrosourea up to 52% at 240 mg/kg, but with ethyl methanesulphonate at up to 400 mg/kg only a few per cent of tumours were obtained. 6. The carcinogenic effectiveness of the agents was positively correlated with the extents of alkylation of guanine in DNA of target tissues at the O-6 atom. On the basis that at doses giving equal carcinogenic response these extents of alkylation would be equal, the chemical analyses showed that the ratio of equipotent doses to that for N-methyl-N-nitrosourea would be, for N-ethyl-N-nitrosourea, 5.3 for ethyl methanesulphonate about 21, and for methyl methanesulphonate [Frei & Lawley (1976) Chem.-Biol. Interact. 13, 215--222] about 144. These predictions were in reasonably good agreement with the observed dose-response data for these agents.

Alkylation↗
PubMed1978

Diagnostic efficacy of tests for the detection of iron overload in chronic liver disease.

The value of tests for the detection of body iron overload was investigated in 8 patients with clinically manifest primary hemochromatosis, 12 patients with cirrhosis and iron overload and 20 patients with liver disease and low or normal iron stores. Iron overload was defined as the presence of stainable iron in more than 50% of hepatocytes in a liver biopsy specimen. The percentages of patients with a true-positive (abnormal) or true-negative (normal) result were: serum iron concentration 65%, transferin saturation 85%, serum ferritin concentration 78%, serum ferritin:serum glutamic oxaloacetic transaminase (SGOT) index 78%, percent iron absorption 58%, percent iron absorption in relation to serum ferritin concentration 80% and percent iron absorption in relation to serum ferritin:SGOT index 93%. The calculated predictive value of a normal test result for the exclusion of iron overload in patients with liver disease, a group with an assumed prevalence of iron overload of 10%, was 98% to 99% for transferrin saturation and serum ferritin concentration used alone and 100% for these measures used together; the predictive value of an abnormal result for the diagnosis of iron overload was less than 50% for all of the above measures used alone or in combination. Hence, in patients with an increased serum ferritin concentration or transferrin saturation, or both, determination of the hepatocellular iron content of a specimen from a percutaneous liver biopsy is required for the diagnosis of iron overload.

Adolescent↗
PubMed1977

Lower limb paralysis induced in mice by a temperature-sensitive mutant of Moloney leukemia virus.

A temperature-sensitive mutant of Moloney murine leukemia virus defective in an early function and injected into newborn mice produced lower limb paralysis. Susceptible mice were inbred strains CFW/D, CBA/H, C3H/Bi/Ka, and outbred NIH Swiss stock. Inbred W/Fu rats and C57BL/Ka mice did not develop the paralysis, though the latter were infected with virus; the sera from these mice produced paralysis in susceptible CFW mice.

Animals↗
PubMed1977

The effect of radiotherapy in the treatment of adenoid cystic carcinoma of the head and neck arising in minor salivary glands.

Eighteen cases of adenoid cystic carcinoma of the minor salivary glands are reviewed. Noteworthy in the history is the report of pain at the site of the lesion which radiates elsewhere, or of numbers or tingling in its area. Radiation therapy is as able to control the primary as local surgery. Involvement of a much wider field than is required to treat the primary may control the perineural spread common to this tumor and avoid the massive procedures necessary to cure it by surgical means. Metastases to the lung, bone, and brain by venous spread can probably be avoided only by early diagnosis.

Adult↗
PubMed1976

Some mechanisms operative in carcinogenesis a review.

Multiple factors contribute to the development of neoplasia. Sometimes a single agency can bring about a tumour if it has many different effects, but at other times a tumour arises more insidiously due to a succession of events [240,241] which by themselves may be innocent. Alterations in the genome of the cell are at the fore-front of our interest because they can be brought about by most of the carcinogenic agents we know. The cell can repair some such alterations but both forward and destructive mutations do appear. The roles of cell proliferation, cell differentiation, the immune mechanism and carcinogen-activating enzymes are beginning to be understood. The effects of dose, route of administration, and of other agents given at the same time [242-245] must not be lost sight of. Other factors no doubt will be added as we begin to look at the structure and function of cell-surface membranes [246-248], at host susceptibility genetics [26, 249], and at the generation of carcinogens inside the body [250,251]. We are only beginning to understand carcinogenesis. In no single instance do we as yet know how a tumour comes about in full details of molecular biology. It is possible that fully rational treatment of cancer will not be possible until we have such an understanding. Once a tumour becomes independent of carcinogenic factors, it continues to develop in a bizarre fashion which makes its study and treatment by all means other than surgery difficult.

Alkylating Agents↗