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Biomedical subjects

J Hendricks

Publications and source records attributed to J Hendricks.

At least 55 records · Page 3Linked to original sources

Expression of ras genes in rainbow trout liver.

Members of the ras gene family have been studied in a variety of species. Two ras genes expressed in the normal liver of rainbow trout, ras-1 and ras-2, as well as a portion of a genomic ras-1 allele, are described for the first time in this report. Over 500 bp of trout ras-1 and at least 300 bp of trout ras-2 genes expressed in normal liver have been sequenced; DNA homology to the human ras genes ranges from 76.8% to 87.1%. The base changes resulting from over 400 million years of evolutionary divergence between the species were primarily silent, with few changes in protein sequence. The partial DNA sequence of the genomic ras-1 allele has 86.8% homology to the first two exons of human c-Ha-ras, and its intron has several conserved sequences characteristic of vertebrate intron-exon junctions. However, the predicted amino acid sequence of trout ras-1 differs at only one of the first 172 amino acid residues from human c-Ki-ras with the alternate exon 4b. Since trout ras-1 differs at 17 and 18 residues from the human c-N-ras and c-Ha-ras proteins, respectively, over this region, we conclude that trout ras-1 is a c-Ki-ras gene. The highly conserved nature of this gene suggests that the ras p21 protein has identical functions in normal and neoplastic cells among higher and lower vertebrates.

Animals↗

Analysis of ras gene mutations in rainbow trout liver tumors initiated by aflatoxin B1.

The suspect human hepatocarcinogen aflatoxin B1 (AFB1) is a well-known potent initiator of hepatic tumors in rainbow trout (Oncorhynchus mykiss). Both hepatocellular carcinomas and mixed hepatocellular/cholangiocellular carcinomas are induced by AFB1 in trout, with the mixed form predominating. We previously isolated two c-ras genes from trout liver cDNA, and in the present study we analyzed DNA from 14 AFB1-induced trout liver tumors for point mutations in exon 1 of both genes. Using the polymerase chain reaction (PCR) and oligonucleotide hybridization methods, a high proportion (10/14) of the AFB1-initiated tumor DNAs showed evidence of activating point mutations in the trout c-Ki-ras gene. Of the 10 mutant ras genotypes, seven were codon 12 GGA----GTA transversions, two were codon 13 GGT----GTT transversions, and one was codon 12 GGA----AGA transition. Nucleotide sequence analysis of cloned PCR products from four of these tumor DNAs provided definitive evidence for two codon 12 GGA----GTA mutations, one codon 12 GGA----AGA mutation, and one codon 13 GGT----GTT mutation, in complete agreement with the oligonucleotide hybridization results. No mutations were detected in exon 1 of a second trout ras gene also expressed in liver, nor in DNA from control livers. This is the first report of experimentally induced ras gene point mutations in a lower vertebrate fish model. The results indicate that the hepatocarcinogen AFB1 induces c-Ki-ras gene mutations in trout similar to those in rat liver tumors.

Adenoma, Bile Duct↗

Laparoscopic cholecystectomy: a multicenter study.

Laparoscopic cholecystectomy has been developed as an alternative to open cholecystectomy for the treatment of symptomatic cholelithiasis. A collaborative study of 261 patients undergoing laparoscopic cholecystectomy at three Texas institutions was performed to determine the effectiveness and safety of this technique. There were 65 males and 196 females with a mean age of 49 years (range 17-94 years). Acute cholecystitis was present in 38 patients and chronic cholecystitis in 223 patients. Mean length of surgery was 80 minutes (20 min to 4 hr). Fifteen patients were converted to the open technique intraoperatively due to bleeding, adhesions, or difficulty of dissection. There were no perioperative deaths and morbidity was 3% including urinary retention, small bowel obstruction, arrhythmia, wound infection, and bile leakage. There were no common duct injuries. Hospitalization ranged from outpatient surgery to 7 postoperative days with a mean of 1.2 days. We conclude that laparoscopic cholecystectomy can be performed safely and with low morbidity and offers shorter hospitalization and postoperative recovery.

Adolescent↗

[Regeneration of bone following thermal injury].

In an animal experiment we could prove, that a spontaneous regeneration of periosteum on thermally injured bone is not to be seen within three month, when the bone is covered by soft tissue only. Using a periosteal flap to cover a burned bone, regeneration could be observed from the endosteum and the periosteum alike. After making the bone with a fluorescent labels, paths and velocity of bony regeneration could be defined.

Animals↗

The effect of intravenous nutrition on muscle mass and exercise capacity in perioperative patients.

This study was undertaken to compare the efficacy of four different types of perioperative intravenous nutritional support. Fifty-five patients undergoing routine major surgery were studied. They were prospectively assigned to one of four study groups. Group 1 received formal total parenteral nutrition (90 g amino acids, 3,000 calories as glucose, per day); Group 2, 100 g glucose per day; Group 3, 90 g amino acids per day; and Group 4, peripheral parenteral nutrition (90 g amino acids plus 1,600 calories, 60 percent as fat per day). Group 1 was maintained on therapy for 3 weeks and the other groups for 8 days. Nitrogen balance, maintenance of body cell mass, serum albumin levels, and maintenance of exercise capacity were measured. Patients receiving peripheral parenteral nutrition maintained their nutritional parameters, as did those receiving total parenteral nutrition. These infusions were both markedly superior to those receiving glucose alone or those receiving amino acids alone. Nitrogen balance was not correlated with maintenance of function, but maintenance of body cell mass was correlated with maintenance of exercise capacity (r = 0.66, p less than or equal to 0.01). We conclude that perioperative peripheral parenteral nutrition, in contradistinction to hypocaloric infusions of glucose or amino acids, is capable of maintaining postoperative muscle mass and function close to preoperative levels after major surgery, and in situations of relatively mild surgical stress, approaches the efficacy of total parenteral nutrition in this regard. A significant correlation exists between changes in body cell mass determined from isotope dilution and changes in the exercise capacity of large muscle masses.

Adult↗

Social dimensions of mental illness among rural elderly populations.

Despite growing concern with rural elderly populations, little attention has focused on their mental health, ways it may correlate with physical health, or how rural mental health patterns compare to urban. Popular wisdom contends that elderly people in general, and rural elderly persons in particular, are at increased risk for mental illness. This article examines these questions. A review of available literature suggests that elderly people may be at only slightly greater risk of mental illness than the population at large, though there are some indications that rates of depression may be somewhat higher among the elderly population. Much of this same literature implies that objective environmental conditions play a significant role in the incidence of depression. Analysis of data gathered in a statewide random poll (N = 743) indicates that while physical health tends to be poorer among rural populations, when health is held constant there is actually an inverse relationship between age and depression. Therefore, rural elderly persons are no more likely to be depressed than their urban counterparts despite harsher living conditions. Both conceptual and policy implications are discussed.

Adolescent↗

Idiopathic hemorrhagic pericardial effusion with organized thrombi in a dog.

A dog was examined because of cardiac tamponade secondary to pericardial effusion. Masses adjacent to the right atrial and ventricular walls were revealed by echocardiography. Pericardectomy and biopsies of the masses established the diagnosis of idiopathic hemorrhagic pericardial effusion with organized thrombi. The dog was healthy 3 months after surgery. These organized thrombi mimicked cardiac neoplasia echocardiographically, and such a possibility should be included in the list of differential diagnoses of cardiac masses.

Animals↗

Metabolism and DNA-binding in vivo of aflatoxin B1 in medaka (Oryzias latipes).

1. The medaka (Oryzias latipes), a small aquarium fish, was shown to possess the capacity to rapidly activate AFB1 in vivo at 25 degrees C to intermediates that bind to DNA. 2. The dose-response for in vivo AFB1-DNA binding was linear over the range 70-550 micrograms AFB1/kg body weight. 3. Maximum binding occurred within the first 24 hr after i.p. injection of [3H]AFB1, followed by a rapid loss of adducts. 4. Aflatoxicol (AFL) and unreacted AFB1 were found by HPLC analysis to be the major products excreted into water after AFB1 exposure, with excretion of AFL as early as 2 min after AFB1 injection. 5. These studies show that medaka possess enzymatic systems similar to rainbow trout (Salmo gairdneri) for biotransformation of AFB1 to the epoxide and to other phase I and phase II metabolites.

Aflatoxin B1↗

Initiation, promotion, and inhibition of carcinogenesis in rainbow trout.

The identification of etiological agents in feral fish neoplasia epizootics has been hampered in part by the lack of suitable fish models, and complicated by the likely existence of environmental agents which can act to stimulate or reduce population responses to genotoxin insult. The response of fish to tumor inhibitors and promoters, and the underlying mechanisms of modulation, have been studied in the rainbow trout model. Dietary treatment of trout with the compounds indole-3-carbinol (I3C), beta-naphthoflavone (BNF), or the polychlorinated biphenyl (PCB) complex Aroclor 1254, before and during exposure to aflatoxin B1 (AFB1), was shown to reduce the final incidence of hepatocellular carcinoma after 12 months, compared to fish receiving AFB1 only. By contrast, treatment of trout with BNF or I3C following AFB1 initiation led to a significant enhancement of ultimate tumor response. Similarly, simultaneous treatment of trout with PCB and the carcinogen N-nitrosodiethylamine led to syncarcinogenic enhancement, rather than inhibition, of tumor response. Mechanisms of inhibition of AFB1 carcinogenesis by PCB, BNF, and I3C were investigated. PCB and BNF, but not I3C, are known to be strong inducers of trout cytochrome P448 and associated activities. Dietary induction by BNF or PCB was shown to be accompanied in isolated hepatocytes by considerably altered AFB1 metabolism, and by significantly reduced rates of DNA adduct formation for all three agents. All agents differentially altered in vivo AFB1 pharmacokinetics, enhanced bile elimination of AFB1 as the aflatoxicol-M1 glucuronide, and significantly reduced peak levels of liver DNA adduct formation. No effects were seen on repair of AFB1-DNA adducts, which was very slow in trout.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Mechanisms of dietary modification of aflatoxin B1 carcinogenesis.

Trout were fed a range of dietary components which altered their carcinogenic response to aflatoxin B1 (AFB1). Dietary protein at levels substantially exceeding nutritional requirements were synergistic with AFB1. Cyclopropene fatty acids (CPFA) were carcinogenic when fed alone at 20 or 55 ppm, and synergistic when fed with AFB1. In contrast, several flavonoid and indole compounds, especially beta-naphthoflavone (beta-NF) and indole-3-carbinol, inhibited the carcinogenic response when fed prior to and along with AFB1. The mechanisms by which some of these dietary factors modulate AFB1 carcinogenesis were investigated. Dietary beta-naphthoflavone was shown to substantially induce the levels of mixed function oxidase (MFO) activities assayed in vitro. These changes were accompanied by alterations in AFB1 metabolism and binding in freshly isolated hepatocytes. AFB1 incubated in hepatocytes freshly isolated from fish fed beta-NF diet was metabolized more rapidly, showed enhanced rates of detoxication reactions, and decreased accumulation of AFB1-DNA adducts compared to control hepatocytes. These results suggest that beta-NF inhibits AFB1 carcinogenesis at least in part by altering MFO activities such that detoxication is enhanced and initial DNA damage by AFB1 is reduced. In contrast, high dietary protein is a synergist for AFB1 carcinogenesis, and this appears to occur primarily by enhancing the transformation probability for AFB1-initiated genome damage. Fish treated with AFB1 as embryos and then reared on high protein diets had substantially higher incidences of hepatocellular carcinoma (86%) than similarly treated fish fed normal protein diet (44%) or high protein controls without AFB1 exposure (0-2%). The synergistic behavior of dietary CPFAs also appears to partially involve enhanced transformation following DNA damage by AFB1. Fish exposed as embryos to AFB1 and then fed CPFA-containing diets are known to show promotion effects similar to the high protein results (Hendricks, J.D., Proc. 11th Int. Symp. of the Princess Takamatsu Cancer Research Fund, in press.) However, factors other than promotion are involved in the synergism between CPFA and AFB1. Preliminary studies indicate that dietary CPFAs repress MFO activities and depress DNA damage by AFB1 in vitro. If this occurs in vivo, then the net synergistic effect of dietary CPFAs would involve depression of initial AFB1-induced DNA damage, but highly efficient promotion of transformation from the remaining lesions.

Aflatoxin B1↗

Developmental models of adult life: myth or reality.

This study investigates the existence of age related life stages and the presumed evolution of attitudes and perceptions in accordance with passages through these successive developmental plateaus. The research utilizes data from six national samples gathered as part of the General Social Survey between 1972 and 1977 by the National Opinion Research Center (N = 9120). Criteria suggested by developmental theorists and other social scientists are employed to examine respondents' life orientation and satisfaction. In most instances age is minimally related to attitudes in these areas while social class and to a lesser extent race and sex emerge as statistically significant and substantively important predictors of these dimensions. The results suggest the difficulties in identifying age related adult life phases through national surveys of attitudes and challenges the underlying assumptions for the existence of uniform age related stages.

Adolescent↗

Attitudes of women and men physicians.

Attitudinal data obtained from interviewing random samples of women and men physicians in metropolitan Detroit indicated that women were generally more liberal and egalitarian than men. Older women were more liberal/egalitarian than older men while younger men were closer in attitudes to younger women. Within specialities, women and men physicians frequently held similar attitudinal scores; however, controlling for age, sex accounted for more variation than did specialty. A weighted combination of variables which together most significantly discriminated between age and sex subgroups pointed to a sensitivity dimension. This was stronger in the women; yet men demonstrating a similar sensitivity were found in almost every age and specialty grouping. Although younger men physicians are less conservative than older men physicians, both younger and older women physicians demonstrated strong liberalism/egalitarianism.

Adult↗

Interaction of concanavalin A with rabbit thymocyte plasma membranes. Distinction between low affinity assoication and positively cooperative binding mediated by a specific glycoprotein.

1. We have analyzed the interaction of the mitogenic lectin, concanavalin A, with purified plasma membranes isolated from rabbit thymocytes. 2. Scatchard analyses show that in native membranes binding is positively cooperative at low concanavalin A concentrations and non-interacting at high lectin levels. 3. In contrast, membranes treated with 0.0064 M glutaraldehyde exhibit diphasic Scatchard plots, indicating the presence of high- and low-affinity binding sites. The high-affinity zone corresponds to the region of positive cooperativity in native membranes. 4. The number of high-affinity binding sites per cell-equivalent corresponds approximately to the number of glycoprotein (mol. wt. 55000) molecules (1-10(6)/cell), but account for less than 25% of the total lectin binding. 5. Treatment of membranes with 0.0064 M glutaraldehyde selectively crosslinks the glycoprotein (mol. wt. 55000) and its multimers, correlating directly with the modifications of concanavalin A-binding. 6. We conclude that high-affinity binding of concanavalin A to thymocyte membranes is a cooperative process mediated by the glycoprotein (mol. wt. 55000). We further conclude that the bulk of concanavalin A binding is through low-affinity associations, not involving specific membrane macromolecules.

Animals↗

Concanavalin A-reactive protein of rabbit thymocyte plasma membranes: analysis by crossed immune electrophoresis and sodium dodecylsulfate/polyacrylamide gel electrophoresis.

1. Thymocyte plasma membrane extracts, prepared with the non-ionic detergent Triton X-100, show 10 major protein components upon sodium dodecysulfate/polyacrylamide gel electrophoresis and at least 11 immunologic components upon crossed immune electrophoresis. 2. Concanavalin A reactive membrane proteins have been identified using crossed immune electrophoresis with receptor-ligand interaction. 3. These proteins are absorbed from Triton X-100-solubilized membranes onto immobilized concanavalin A. They are eluted in stepwise fashion, using increasing concentrations of alpha-methyl-d-glucoside, between 0.0004 M and 0.1 M. The predominant proteins eluted in each step are components with high electrophoretic mobility in crossed immune electrophoresis and are identical with a glycosylated component in sodium dodecysulfate/polyacrylamide gel electrophoresis with molecular weight of 55 000. 4. This component forms multimers in the presence of Triton X-100 which are not totally dissociated in sodium dodecylsulfate. 5. Neuramidase treatment followed by crossed immune electrophoresis of total plasma membrane isolates, as well as the purified glycoprotein fraction, indicates that the concanavalin A-reactive proteins are sialoglycoproteins. 6. Sodium dodecylsulfate component 5.1 comprises at least two different populations of glycoproteins (6 and 9) in crossed immune electrophoresis, one of which exclusively exhibits heterogenous carbohydrate antigenic sites (component 9). 7. Present data, taken together with previously published experiments, indicate that concanavalin A binding to intact thymocytes induces an increased turnover and release of the receptor protein(s).

Animals↗