PubMed Health⌕ Search

Biomedical subjects

J Searle

Publications and source records attributed to J Searle.

At least 19 recordsLinked to original sources
PubMed1992

Loss of heterozygosity at the human RAP1A/Krev-1 locus is a rare event in colorectal tumors.

Kirsten-ras-revertant-1 (Krev-1/Rap1A) is a recently identified tumor suppressor gene which induces flat revertants when introduced into a variety of ras-transformed cell lines in vitro. Since 47% of colorectal carcinomas have transforming mutations in ras protooncogenes, and since Krev-1 is expressed at high levels in normal colonic mucosa, we hypothesized that inactivation at the Krev-1 locus may be necessary for transformation of colonic cells. Loss of heterozygosity is a common method of inactivation of tumor suppressor genes in colorectal tumors. Therefore, we analyzed loss of heterozygosity in 52 patients with sporadic colorectal cancer. Because Krev-1 had no previously described polymorphisms, we first identified a BclI restriction fragment length polymorphism which showed 40% heterozygosity in 50 unrelated individuals. However, only one tumor from 18 informative patients showed allelic loss at the Krev-1 locus. This suggests that loss of heterozygosity is not a common mechanism of inactivation at the Krev-1 locus in colorectal cancer. However, the results do not exclude a role for Krev-1 in the etiology of this neoplasm because inactivation may occur by other mechanisms.

Alkaline Phosphatase↗
PubMed1991

Multiple paternity in wild common shrews (Sorex araneus) is confirmed by DNA-fingerprinting.

We have tested for the occurrence of multiple paternity in wild common shrews by karyotypic analysis and DNA-fingerprinting of five wild-caught females and their litters. Karyotypic data suggest that some litters were sired by more than one male, but provide no definitive evidence. By using DNA-fingerprinting, it was possible to establish that two males sired the litter of two females. The present report shows that multiple paternity is not a rare phenomenon in the common shrew and by using DNA-fingerprinting it is possible to assign individual offspring to different male parents even when none of the putative fathers are available for inspection.

Animals↗
PubMed1990

The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years.

Forty-two patients with nonalcoholic steatohepatitis were followed for a median of 4.5 yr (range = 1.5 to 21.5 yr). Except for two patients with lipodystrophy, all were obese; 35 of 42 were women, 26 of 32 were hyperlipidemic and 15 were hyperglycemic. Upper abdominal pain was the most common reason for presentation. Initial liver biopsy specimens showed the presence of macrovesicular fatty infiltration, lobular (acinar) inflammation, apoptosis, Mallory bodies (in four cases) and fibrosis (in 18 cases). Cirrhosis was present at initial diagnosis in one subject and in another two subjects liver biopsy showed marked fibrosis with disturbed architecture. Serial liver biopsy specimens revealed minimal or no apparent progression of the disorder in most of the patients, in keeping with their benign clinical course. However, one patient showed progression from fibrosis to cirrhosis during the 5-yr observation period, and in the patients with extensive fibrosis the liver disease evolved from one of active inflammation to one of inactive cirrhosis without fat or inflammation. The patient with cirrhosis later died of hepatocellular carcinoma. The severity or type of hepatic change did not correlate with the degree of obesity, hyperlipidemia or hyperglycemia. However, in individual patients, poorly controlled diabetes and rapid weight loss preceded the onset of steatohepatitis. We conclude that nonalcoholic steatohepatitis is a cause of hepatic inflammation histologically resembling that of alcohol-induced liver disease but usually slowly progressive and of low-grade severity. However, the disorder may ultimately result in cirrhosis. Nonalcoholic steatohepatitis should be distinguished from alcoholic steatohepatitis and recognized as a further cause of "cryptogenic cirrhosis."

Adolescent↗
PubMed1990

Cyclosporin-responsive enteropathy and protracted diarrhea.

We describe a child born to unrelated parents who developed severe protracted secretory type diarrhea associated with subtotal villus atrophy and intestinal inflammation at the age of 19 months. No infectious, metabolic, or anatomical basis for this condition was identified and the child required total parenteral nutrition for a period of 18 months despite trials of special enteral formulas, steroids, and anti-inflammatory agents. This refractory "enteropathy" responded dramatically to the introduction of cyclosporin, with cessation of the secretory diarrhea, recovery from the enteropathy, and cessation of parenteral nutrition. The symptoms relapsed when cyclosporin was briefly discontinued and improved following reintroduction of this drug. This experience suggests a role for immune factors in the pathogenesis of the enteropathy in this case and that a trial of cyclosporin is worthy of consideration in similar cases.

Cyclosporins↗
PubMed1990

Familial iron overload with possible autosomal dominant inheritance.

A 96 member Melanesian kindred with 31 cases of iron overload is reported. Liver biopsies from 19 of these patients showed features similar to those of genetic haemochromatosis in Caucasians, but in contrast to the previous reported HLA-linked autosomal recessive pattern of inheritance for haemochromatosis, this family shows a pattern that is most consistent with autosomal dominant inheritance. This is suggested by involvement of three and possibly four consecutive generations, with a high frequency of transmission from parents to children and equal gender distribution. Linkage and segregation analysis supported dominant inheritance, with no demonstrable HLA linkage.

Female↗
PubMed1989

Steatohepatitis associated with limb lipodystrophy.

Two patients who presented with steatohepatitis had acquired partial lipodystrophy. This association has not previously been well documented. A common pathophysiological mechanism in lipodystrophy, obesity-associated nonalcoholic steatohepatitis, and alcoholic liver disease is possible.

Adolescent↗
PubMed1989

Dirofilariasis in Australia: unusual cause of a breast lump.

A breast lump due to infestation with Dirofilaria repens is reported in a Sri Lankan student residing in Brisbane. Although human infestation with this parasite is not uncommon in certain Asian countries, this is the first report of such a lesion occurring in Australia.

Adult↗
PubMed1988

Neonatal hemochromatosis: a case and review of the literature.

Hemochromatosis is a disease in which the inappropriate absorption of iron over 30-40 yr results in tissue iron overload and the development of cirrhosis of the liver, diabetes, hypogonadism, arthropathy, and skin pigmentation. We present an infant who died at 2 days of age, and who was found to have massive iron overload in the liver. This case is consistent with a rare condition that has been called neonatal hemochromatosis. This disease is discussed in the context of an overview of iron metabolism and adult hemochromatosis.

Hemochromatosis↗
PubMed1987

Fetal biophysical testing. The effects of prolonged maternal fasting and the oral glucose tolerance test.

Fetal biophysical testing incorporates observations of the fetal heart rate (FHR), fetal breathing movements (FBMs) and fetal trunkal movements (FTMs). These parameters were examined during maternal fasting and glucose loading. Thirty normal term gravidas were studied during a 210-minute session, of which the first 30 minutes served as a fasting control period, following which 20 (group G) received 100 g oral glucose, while 10 (group F) continued fasting. Serum glucose levels in both groups were determined every 30 minutes. FHR, FBMs and FTMs were recorded concurrently using abdominal electrocardiography and real-time ultrasonography and entered on line into a microcomputer. Offline data analysis provided mean 30-minute baseline FHRs, acceleration counts, FBM incidences, FBM rates and FTM incidences. Both groups were similar for gestational age, birth weight and perinatal outcomes. Mean 30-minute FHR baseline was unchanged and similar in both groups. Mean 30-minute FHR acceleration counts and FTM incidences were significantly higher in group F, while FBM incidences and rates were significantly higher in group G. While biophysical testing can be conducted under either set of maternal conditions, different normal standards must be employed, test length must be sufficient to account for normal biologic variations, and biophysical parameters must be monitored concurrently.

Electrocardiography↗
PubMed1987

Clinical significance of fetal tachypnea during antepartum biophysical testing.

Fetal tachypnea has been regarded as a rare finding with a poor perinatal prognosis. Eighteen cases of fetal tachypnea were noted during the biophysical tests of 200 patients. Biophysical testing consisted of concurrent ultrasound observations of fetal breathing and body movements and electronic monitoring of fetal heart rate, coupled with determinations of fetal tone and amniotic fluid volume. Fetal breathing movement frequency and rate, fetal trunkal movement frequency, and baseline fetal heart rate were analyzed on a programmed microcomputer. The mean (+/- SD) breathing rate was 68.2 +/- 6.4 breaths per minute; mean breathing frequency, 55 +/- 22.6%; mean baseline heart rate, 141 +/- 8 beats per minute; mean trunkal movement incidence, 5.5 +/- 2.6%; and mean acceleration frequency, 14.6 +/- 9.8 per hour. No fetus was apneic for more than eight minutes, and there were no significant correlations between fetal breath rates and the other biophysical parameters. There were no perinatal deaths. Seven fetuses experienced perinatal morbidity, of whom five had other abnormalities on biophysical testing. This study indicates that fetal tachypnea occurs more often than previously believed and does not generally signify fetal compromise unless other biophysical abnormalities are also present.

Female↗
PubMed1985

Computer-assisted assessment of the fetal biophysical profile.

The biophysical profile assesses fetal heart rate, breathing movements, fetal body movements, amniotic fluid volume, and fetal tone. In the past, these data have been scored by an arbitrary, unweighted system. While this approach is useful in detecting major anomalies and oligohydramnios, both static observations, the dynamic variables (fetal heart rate, fetal breathing movements, and fetal body movements) have added little information beyond that of an extended nonstress test alone. We have evaluated an alternative biophysical assessment system, modeled after extended physiologic studies, which not only acquires dynamic fetal variables simultaneously but, with computer assistance, quantifies the biophysical information. With an ADR 4000/L scanner, a Hewlett-Packard 8040 A monitor, and a specially programmed IBM microcomputer, we studied 100 normal term fetuses during 60-minute epochs. Each gestation had normal amniotic fluid volume and fetal tone. Normative values for the dynamic variables, expressed as means +/- SD were: fetal heart rate, 137 +/- 6.3 bpm; incidence of fetal breathing movements, 25.0% +/- 17.3%; rate of fetal breathing movements, 46.0 +/- 9.4 breaths/min; total fetal breathing movements, 823 +/- 61; incidence of fetal body movements, 8.5% +/- 3.9%; accelerations (greater than 15 bpm, 15 seconds), 14.1 +/- 6.3. We conclude that this approach is practicable, respects the biologic cycles of fetal behavior, and provides a basis for population standards and sequential study of the same fetus.

Amniotic Fluid↗
PubMed1985

Renal abnormalities and spondylometaphyseal dysplasia.

A renal lesion has not been previously described in association with spondylometaphyseal dysplasia. A case of nephrotic syndrome with progression to renal failure from focal segmental glomerulosclerosis is described.

Child↗
PubMed1985

Sulindac hepatotoxicity: effects of acute and chronic exposure.

Sulindac (Clinoril), an anti-inflammatory drug increasingly used in Australia for the treatment of rheumatological conditions, is unpredictably associated with a cholestatic hepatitis. We present three cases of sulindac hepatitis. The first case exemplifies acute sulindac hepatitis, the second, continuously exposed to sulindac for 18 months, had chronic sulindac hepatotoxicity, and in the third case, the long-term histological outcome after cessation of sulindac is described. The clinical, biochemical, and histopathological characteristics are those of a cholestatic hepatitis which resolves on withdrawal of the drug. We report marked anisonucleosis with cytoplasmic invaginations into the nucleus and binuclearity of hepatocytes as additional histological features of sulindac hepatitis. There is no evidence that sulindac hepatitis progresses to irreversible structural liver damage, although nuclear changes may persist for up to two months after cessation of the drug. The clinical and biochemical features of all reported cases of sulindac hepatitis are summarised.

Adult↗
PubMed1985

Valproate hepatotoxicity: a review and report of two instances in adults.

Two patients with severe liver damage induced by sodium valproate are described. Both were adults. One had taken valproate for longer than one year before complications developed. The other, in whom the disorder was fatal, had a predominantly 'hepatic' pattern of liver damage with centrilobular necrosis and he also developed pancreatitis. The first patient, who recovered following cessation of valproate intake, manifested a predominantly cholestatic illness with portal tract inflammation. In addition he had a degree of reversible renal failure. Neither subject had microvesicular steatosis on liver biopsy. This report indicates that valproate hepatotoxicity is not always confined to children, that it may develop much later in the course of valproate therapy than has been previously recognized, that it is not necessarily fatal if valproate intake is ceased early enough, and that it may be associated with reversible renal insufficiency.

Adolescent↗
PubMed1985

The detection of IgG anti-hepatocyte antibodies by ELISA in sera of patients with chronic active hepatitis: correlation with disease activity.

Anti-hepatocyte membrane IgG antibodies were detected in serial dilutions of sera from patients with chronic active hepatitis using an enzyme linked immunosorbent assay with isolated rat hepatocytes as the antigenic substrate. The assay is rapid, reliable and reproducible. Antibodies to hepatocyte membrane antigens were detected in 24 out of 31 (77%) patients with autoimmune chronic active hepatitis. Four of these patients were negative in a 1/10 dilution but became positive on progressive dilution. In 12 patients, liver biopsy was performed at the same time as serum was obtained. In these patients, the titre of antibodies to hepatocyte membrane antigen correlated significantly with the overall biopsy score of disease activity and particularly with the degree of portal tract infiltration. In 2 patients followed serially, titres of anti-hepatocyte membrane antibodies fell progressively in parallel with clinical, biochemical and histological evidence of improvement in the liver disease. The estimation of titres of antibodies to hepatocyte membrane antigens using isolated rat hepatocytes as the antigenic substrate may assist in the diagnosis, assessment of disease activity and follow-up of individual patients with chronic active hepatitis.

Autoantibodies↗
PubMed1984

The role of apoptosis in atrophy of the small gut mucosa produced by repeated administration of cytosine arabinoside.

Progressive atrophy of ileal crypts and villi following daily administration of cytosine arabinoside to mice was found to be the result of suppression of mitosis and marked enhancement of apoptosis in the crypt epithelium. The amount of apoptosis produced by each dose decreased as the atrophy advanced. Mucosal regeneration after cessation of administration of the drug was due to increased mitosis in the crypts, and was associated with complete restoration of susceptibility of the crypt cells to further doses. During early regeneration, the wave of increased mitosis was accompanied by a wave of mildly increased apoptosis.

Animals↗