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Biomedical subjects

R Rubin

Publications and source records attributed to R Rubin.

At least 19 recordsLinked to original sources
PubMed1992

Antitumor effect of deferoxamine on human hepatocellular carcinoma growing in athymic nude mice.

BACKGROUND: Iron is essential for the growth of all living cells. One of the important intracellular roles for iron is in the activation of ribonucleotide reductase, the enzyme that catalyzes the first step in DNA synthesis. Thus, the intracellular iron level may serve as a regulator of cell growth. The authors tested the hypothesis that lowering body iron concentration inhibits the growth of human-derived hepatocellular carcinoma (HCC) cells by depleting these cells of iron. Deferoxamine (DFO), an iron-chelating agent, was used to lower intracellular iron level. METHODS: HCC cells, PLC/PRF/5 (7 x 10(6) cells/mouse), were transplanted subcutaneously into athymic nude mice. When tumors reached 200-300 microliters in size, mice with comparable tumor sizes were paired; one was treated with DFO (300 mg/kg body weight/day, 5 days/week) intraperitoneally while the other received no treatment. RESULTS: Eight pairs of mice with HCC were observed for 5-18 weeks. Mean tumor growth rates (TGR) (mean +/- standard error) for the untreated and treated mice were 30.5 +/- 3.7 microliters/week and 11.9 +/- 1.5 microliters/week. The difference was significant (P < 0.02). In the second set of studies, DFO treatment was begun when the tumor size was smaller (100-200 microliters). Four pairs of mice were observed for 4-15 weeks; mean TGR for the four untreated mice was 18.1 +/- 5.1 microliters/week. In two mice treated with DFO, tumors regressed completely by the seventh week after initiation of treatment. The two remaining mice on DFO therapy had much slower growing tumors, with a mean TGR of 1.8 +/- 0.5 microliters/week. CONCLUSIONS: Thus, our results suggest that (1) reduction of intracellular iron concentration by DFO may be useful as antitumor therapy in HCC and (2) the favorable effects of DFO treatment are best seen when treatment is begun when the tumor is small.

Animals↗
PubMed1992

Effect of ethanol on platelet phospholipase A2.

Platelet aggregation is known to be inhibited by ethanol, and this has been suggested to be one of the attenuating effects of ethanol in cardiovascular disease. Recent studies have implicated an inhibition of phospholipase A2 induced arachidonic acid release, since the production of prostanoids that are formed from arachidonic acid and are involved in the aggregation process has been shown to be diminished by ethanol. Phospholipase A2 is found in platelets in both a cytosolic form, from where it may translocate to the plasma membrane to release arachidonic acid, and in a secretory form which is released extracellularly upon activation. In the present study, the effect of ethanol on the secretion of phospholipase A2 and on its activity was determined. It was found that ethanol inhibited phospholipase A2 secretion but not its activity. By contrast, the activity of the cytosolic form of phospholipase A2 was inhibited by ethanol.

Animals↗
PubMed1992

An improved technique for isolated perfusion of rat livers and an evaluation of perfusates.

We have modified the apparatus for isolated rat liver perfusion (IPRL) in order to be able to perform two perfusions simultaneously. In addition, we studied the quality and stability of livers by comparison of five different perfusates: Blood (Group A), Original Krebs Henseleit buffer (Group B), Krebs buffer with glucose (Group C) or bovine serum albumin (BSA) added, (Group D). In a last group (E) albumin, glucose, and taurocholic acid were added to Krebs. After 180 min of perfusion, livers perfused with solutions including 2% albumin (Group D, E) had a significantly higher release of hepatocellular and endothelial cell (purine nucleoside phosphorylase) enzymes and lower bile production as compared to Groups A, B, and C (P less than 0.0001). Increasing levels of purine nucleoside phosphorylase (PNP), a reflection of damage to the microvascular endothelium preceded the increases in hepatocellular enzymes. Histologically, damages of sinusoidal endothelial cells and hepatocytes are appreciated moderate to severe in Groups D and E, slight to mild in Groups A and B, and not significant in Group C. These results suggest that BSA may have toxic effects to the perfused rat liver. These data also confirm that the IPRL modified for simultaneous perfusion of two livers is efficient, and that with this technique the rat liver can be optimally perfused for up to 3 hr with oxygenated Krebs Henseleit buffer without additives (Group B) and without blood. These two improvements should allow those performing studies with perfused rat livers to obtain data in a more efficient, accurate, and inexpensive fashion.

Animals↗
PubMed1992

Mass-like hepatic hypertrophy: MRI findings with histologic correlation.

Hepatic parenchyma may hypertrophy following asymmetrical injury. The histologic characteristics of hypertrophic hepatic parenchyma are more similar to normal hepatic parenchyma than is the more severely damaged liver. We present four cases where large hypertrophic masses resembled neoplasm on other imaging modalities or at surgery, but had MRI signal characteristics similar to those of normal liver.

Adult↗
PubMed1992

Aneurysms of the carotid arteries associated with von Recklinghausen's neurofibromatosis.

Aneurysms of both common carotid arteries were seen in a patient with neurofibromatosis. Histologic examination of the involved arteries demonstrated a dense proliferation of spindle cells within the arterial walls accompanied by medial cystic degeneration and disruption of the tunica elastica. These changes were also observed in adjacent, grossly uninvolved segments of the blood vessels. Immunohistochemical analysis of the proliferating cells was positive with antibodies against desmin and muscle-specific actin. The findings demonstrate and confirm the smooth muscle origin of the aberrant proliferated cell population in arteries in a patient with von Recklinghausen's neurofibromatosis.

Adult↗
PubMed1992

Evidence for a novel route of wheat storage proteins to vacuoles.

Wheat seed storage proteins are deposited in protein bodies (PB) inside vacuoles, but their subcellular site of aggregation and their route to vacuoles are still controversial. In the present work, an ultra structural analysis of developing wheat endosperm at early to mid maturation was performed to address these issues. Golgi complexes were rarely detected, indicating that their role in wheat storage protein transport is limited. In contrast, a considerable amount of PB was detected in the cytoplasm. Many of these PB were surrounded by RER membranes and were enlarged by fusion of smaller PB. Small, electron lucent vesicles were detected around the surfaces of the PB in the cytoplasm, or attached to them, suggesting that such attachments and subsequent fusion of the vesicles with each other lead to the formation of small vacuoles containing PB inclusions. Immunogold labeling with serum raised against yeast-BiP, an ER-localized protein, demonstrated that the wheat BiP homolog was present within the PB in the cytoplasm as well as inside vacuoles. This confirmed that the PB were formed within the RER and that the Golgi complex was not involved in their transport to vacuoles. It is concluded that a considerable part of the wheat storage proteins aggregate into PB within the RER and are then transported as intact PB to the vacuoles by a novel route that does not utilize the Golgi complex.

Biological Transport↗
PubMed1992

Azole therapy for trichosporonosis: clinical evaluation of eight patients, experimental therapy for murine infection, and review.

We studied the in vivo antifungal activity of azoles in humans and in a murine model of disseminated trichosporonosis. Eight patients infected with Trichosporon species were treated with fluconazole, SCH 39304, or miconazole for 2-26 weeks. Four patients had fungemia, two patients had disseminated trichosporonosis, and one patient each had soft-tissue infection and cystitis. Response of trichosporonosis to azoles was seen in all eight patients, although one patient died with disseminated aspergillosis while still receiving SCH 39304. A literature review indicated that responses to ketoconazole or miconazole were noted in four patients with trichosporonosis. In the experimental infection, amphotericin B, SCH 39304, and fluconazole were effective in prolonging survival and reducing fungal counts in the kidneys of mice infected with a clinical strain of Trichosporon beigelii. Fluconazole but not amphotericin B prolonged survival of mice infected with a clinical strain of Trichosporon capitatum. We conclude that azoles represent effective therapy for infection with Trichosporon species.

Adult↗
PubMed1992

Suprahepatic circumcaval ring: CT finding after orthotopic liver transplantation.

A suprahepatic circumcaval ring or arc was noted on computed tomographic (CT) scans in 20 of 37 patients who had undergone 42 orthotopic liver transplantations. The patients were divided into two groups, depending on the presence or absence of this finding. The amounts of blood products transfused intraoperatively and the levels of serum calcium, phosphate, and calcium phosphate product after transplantation were determined for each group. Liver graft function was evaluated on the basis of postoperative levels of serum bilirubin, albumin, and aminotransferase. The levels of serum calcium and calcium phosphate product were higher in patients with the circumcaval ring. This group had received substantially more fresh frozen plasma and platelets at surgery. There was no difference in liver graft function between the two groups. In one case, pathologic examination demonstrated calcification within circumcaval fibrotic tissue. A suprahepatic circumcaval ring is a common finding at CT performed after liver transplantation and is probably related to elevated perioperative serum calcium levels and tissue injury. Surgeons should be made aware of this finding before performing repeat transplantation, since calcification at a potential anastomotic site may make surgery more difficult.

Adolescent↗
PubMed1992

Comparison of dosage schedules of rt-PA in the treatment of proximal deep vein thrombosis.

This study assessed the efficacy and safety of increasing durations of constant-dose intravenous recombinant tissue-type plasminogen activator (rt-PA) in the treatment of deep vein thrombosis. Patients with venogram-documented proximal lower limb (popliteal, iliofemoral) or upper limb (axillary, subclavian) thrombi were given an initial 2-hour rt-PA infusion at 4 micrograms/kg/min, followed by a maintenance infusion of 1 microgram/kg/min for an additional 4, 22, or 33 hours (mean total rt-PA dosages of 54, 127, and 185 mg). A new quantitative venogram scoring system was applied to the study, based on measurements of thrombus volume before and after completion of treatment. Whereas none of the seven patients given treatment for 6 hours and only one of four given treatment for 24 hours showed significant lysis, four of seven who received a prolonged infusion for 35 hours showed lysis of more than 40% of the original thrombus. Overall, the prolonged 35-hour infusion induced 51% lysis of original thrombus, representing a thrombus volume of 16.7 ml dissolved. Hemorrhagic complications were common in all three groups, with four of 18 patients having significant bleeding, including one massive gastrointestinal hemorrhage, two patients with a decrease in hematocrit of more than 10%, and one patient with an intracranial hemorrhage who recovered completely. Pharmacokinetics of the rt-PA showed a steady state antigen concentration of 240 ng/ml and activity of 200 IU/ml during the initial 2-hour infusion and a postinfusion half-life of 5 minutes. Plasma fibrinogen concentrations decreased to approximately 40% to 50% of initial values with all three treatment regimens, but the nadir fibrinogen concentrations did not correlate with either therapeutic efficacy or bleeding complications. One patient with systemic lupus erythematosus had an unusual allergic reaction that manifested primarily as angioedema. This study suggests that rt-PA infusion of 35 hours induces greater thrombolysis of deep vein thrombosis than does a shorter course of 6 or 24 hours, without an increase in hemorrhagic complications.

Adult↗
PubMed1991

Neurobehavioral effects of the on-call experience in housestaff physicians.

Sixty-tree medical residents were tested on a battery of computer-based, self-administered neurobehavioral tests before and after a 36-hour in-hospital call plus postcall day to assess the central nervous system effects of the call experience and its accompanying sleep deprivation. Statistically significant decreases in performance were found postcall on tests of sustained visual attention (P less than 0.0001), speed and coding ability (P less than 0.0001) and short-term recall (P less than 0.0001). Hand-eye coordination improved (P less than 0.02).

Humans↗
PubMed1991

Hepatocellular carcinoma within siderotic regenerative nodules: appearance as a nodule within a nodule on MR images.

Large regenerative nodules in cirrhotic livers may accumulate iron and develop internal iron-poor foci of hyperplasia or malignancy. Magnetic resonance examinations were performed on 23 patients with biopsy-proved cirrhosis. A "nodule-within-nodule" appearance was noted in two patients. This appearance consisted of markedly low intensity of a large nodule on gradient-echo images, with one or two internal foci that were isointense to the liver. Each of the large nodules was 2 cm in diameter, and each of the internal foci was less than 1 cm. Serum alpha-fetoprotein levels were normal in both patients. Aspiration biopsy performed in one patient failed to show malignancy, but histologic confirmation of hepatocellular carcinoma was obtained eventually in both cases. The nodule-within-nodule sign, which reflects the unique histopathology of hepatocellular carcinoma in large siderotic regenerative nodules, is strongly suggestive of early hepatocellular carcinoma, even if serologic markers and biopsy results do not support this diagnosis.

Biopsy↗
PubMed1991

Parenchymal versus reticuloendothelial iron overload in the liver: distinction with MR imaging.

Parenchymal iron deposition occurs in hemochromatosis, while iron is deposited in reticuloendothelial (RE) cells after blood transfusions or rhabdomyolysis. Magnetic resonance images of patients with decreased liver signal intensity on T2-weighted images at 1.5 T were blindly compared in an effort to distinguish these conditions. In each of five patients with hemochromatosis, the pancreas had low signal intensity, but splenic signal intensity was decreased in only one. In contrast, only three of the 16 patients with RE iron overload had low pancreatic signal intensity, while all of these patients either had low splenic signal intensity (n = 14) or previously underwent splenectomy (n = 2). Distinction among these causes of iron deposition is clinically important because parenchymal iron overload from hemochromatosis may produce significant tissue damage, while the RE iron of transfusions and rhabdomyolysis is of little clinical consequence.

Adolescent↗
PubMed1991

Fatty liver. Chemical shift phase-difference and suppression magnetic resonance imaging techniques in animals, phantoms, and humans.

In vitro animal and human models were used to evaluate the potential of chemical shift magnetic resonance imaging (MRI) for assessing fatty liver. Phantoms of varying fat content were created from mayonnaise-agar preparations. Fatty liver was induced in eight rats by feeding them ethanol for three to six weeks (36% of total calories), whereas eight control rats were fed a normal diet. T1-weighted in-phase and opposed-phase MR images were obtained of the phantoms animals, and 28 human subjects. Additional images obtained in animals included long TR images with in-phase and opposed-phase technique, and hybrid chemical shift water and fat suppression. The rats were killed and histologic status was graded blindly by a hepatopathologist as normal, mild, moderate, or severe fatty change, for correlation with MR grading. Quantitative analysis of MR images included fat signal fraction for animals, and relative signal decrease between in-phase and opposed-phase images for phantom and human data. Phantom in-phase signal increased linearly with respect to fat content, whereas opposed-phase signal decreased linearly. MRI and histologic grading of rat livers were highly correlated, especially when based on water suppression images (r = 0.91, P = .0001). Opposed-phase images were also highly correlated, while fat suppression images were less effective. There was no overlap between MR-derived fat fractions for control (2.6%-5.7%) versus ethanol-fed rats (7.7%-17.9%, P = .0002). Human liver considered to be fatty by visual inspection (n = 8) had higher relative signal decrease than nonfatty liver (n = 22) (P less than .001). Phantom, animal, and human data demonstrate that comparison of T1-weighted in-phase and opposed-phase images is both practical and sensitive in the detection and grading of fatty liver.

Adult↗
PubMed1991

Recurrence of hepatitis C virus infection after orthotopic liver transplantation.

Identification of the hepatitis C virus--the main cause of posttransfusion and sporadic non-A, non-B hepatitis--and the development of a diagnostic serological test have allowed us to study possible recurrence of this type of hepatitis after liver transplantation. Six of 34 consecutive transplant recipients were found to have had antibodies to hepatitis C before transplantation. All six patients had possible exposure to hepatitis C through blood transfusion or intravenous drug use. Five of the six patients were positive for antibodies to hepatitis C after 1 yr of follow-up. Two of these patients had clinical and histological evidence of acute viral hepatitis in their allografts. In one patient this led to hepatic injury and dysfunction of two successive grafts. In contrast, none of the twenty-eight patients who were seronegative for hepatitis C virus antibodies before transplantation has converted to seropositivity after transplantation despite perioperative blood transfusions. These results suggest that hepatitis C diagnosed serologically recurs in a minority of transplant recipients and that de novo seroconversion must be uncommon.

Adult↗
PubMed1990

Effect of guanine nucleotides on polyphosphoinositide synthesis in rat liver plasma membranes.

The effect of guanosine 5'-[gamma-thio]triphosphate (GTP[S]) on PtdIns and PtdIns(4)P kinase activities was measured in rat liver plasma membranes. The addition of [32P]ATP resulted in the rapid incorporation of 32P into PtdIns(4)P and PtdIns(4,5)P2, with maximal levels reached within 30 s. GTP[S] (25-500 microM) increased the rate and magnitude of [32P]PtdIns(4)P and [32P]PtdIns(4,5)P2 formation by 50 and 120% respectively. Similar stimulatory effects were induced by guanosine 5'-[beta gamma-imido]triphosphate, GTP, GDP and guanosine 5'-[beta-thio]diphosphate. The stimulation of PtdIns phosphorylation by GTP[S] occurred in the presence of 2 mM-EGTA, a condition which fully inhibited phosphoinositide-specific phospholipase C. GTP[S] did not stimulate phosphomonoesterase activity, and its action was not due to the binding of magnesium. However, the overall ATP-hydrolysing activity of the membrane preparation was inhibited by GTP[S] and the other guanine nucleotides. There was a direct correlation between the extent of this inhibition and the stimulation of polyphosphoinositide formation. The results indicate that stimulation of polyphosphoinositide formation by guanine nucleotides in rat liver plasma membranes can be accounted for by an inhibition of ATP hydrolysis. These data are inconsistent with a specific GTP-binding protein (G-protein)-mediated stimulation of PtdIns or PtdIns(4)P kinase.

Adenosine Triphosphate↗