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Biomedical subjects

H Solomon

Publications and source records attributed to H Solomon.

At least 55 records · Page 3Linked to original sources
PubMed1996

p53 abnormalities in hepatocellular carcinoma from United States patients: analysis of all 11 exons.

Mutations of the tumor suppressor gene p53 have been found in hepatocellular carcinomas (HCCs) from many countries where HCC is common, but p53 mutations detected by direct sequencing in HCCs from the United States (where HCC is uncommon) have been reported only rarely. p53 Exons 1 to 11 were analyzed by polymerase chain reaction, single-strand conformation polymorphism analysis, and direct sequencing in HCCs from 12 patients from the United States and in adjacent non-tumorous liver from 10 of them. Abnormalities of the p53 gene were found in five of the 12 tumors, including mutations in exon 4 (one patient), exon 5 (one patient) and exon 8 (three patients). In all 12 tumors, a normal conformation of exon 7 was found; in five of these HCCs the absence of mutations was confirmed by direct sequencing. Thus, the mutations of p53 codon 249 that have frequently been found in HCCs from endemic areas apparently do not play a role in most HCCs in the United States. Since the mutations in codon 249 are thought to be due to aflatoxin ingestion, the data suggest that factors other than aflatoxin may be responsible for the p53 abnormalities in the patients from the USA.

Adolescent↗
PubMed1996

The effect of high-dose right upper quadrant lithotripsy on normal swine tissue.

To assess the effects of high doses of shock waves to organs in the right upper quadrant of the abdomen, 36 adolescent swine were given one treatment of either 2,000 (2k), 6,000 (6k), or 10,000 (10k) shock waves at 24 kV peak pressure using a spark-gap lithotriptor. Shock waves were sonographically focused on the lumen of the gallbladder. Blood and tissue were examined for each group at 48 hours, at 35 days, and at 6 months. This study showed that administration of up to five times the accepted upper limit of shock waves produced no permanent damage. Transient injury, most commonly hematoma, was encountered. No posttreatment intra-abdominal catastrophes occurred. Although no renal injury was seen, it should be noted that the focus of maximum energy was 5 cm cephalad to the right kidney. This study suggests that an increased number of shock waves may be administered safely to this area of the abdomen.

Animals↗
PubMed1996

Pancreaticocystostomy revision for obstructive pancreatitis and pancreatic fistula after segmental pancreatic transplantation.

Combined kidney-pancreas transplantation is an effective surgical therapy for end-stage renal failure secondary to type I diabetes mellitus. However, obstructive pancreatitis and pancreaticocutaneous fistula remain significant postoperative complications unique to extraperitoneal segmental pancreatic transplantation. We present our experience with 13 patients (7 with obstructive pancreatitis and 6 with pancreaticocutaneous fistulae) after segmental extraperitoneal pancreatic transplantation, who subsequently underwent intraperitoneal reconstruction of the pancreaticocystostomy. This reconstruction was successful in 11 of 13 (85%) patients with minimal morbidity and no mortality. This intraperitoneal approach to reconstruction of the pancreaticocystostomy after segmental extraperitoneal pancreatic transplantation is a safe and effective means of graft salvage and this technique has not been described in the literature.

Adult↗
PubMed1995

Regulation of retinoblastoma gene expression in hormone-dependent breast cancer.

Studies have shown an increased risk for breast cancer in the mothers of children suffering from retinoblastoma and osteosarcoma, suggesting a role for the retinoblastoma susceptibility (Rb) gene product in breast cancer. We now show that estradiol decreases the expression of Rb at the level of protein and messenger RNA (mRNA) in estrogen-dependent breast cancer cell lines. Treatment of MCF-7 cells with 10(-9) M estradiol for 48 h resulted in a 70% decrease in the level of Rb protein. Ribonuclease protection assays showed a 50% decrease in the steady state levels of Rb mRNA by 12 h and a 70% decrease in Rb mRNA by 24 h. Treatment with estradiol had no effect on the rate of Rb gene transcription or on Rb mRNA stability, but resulted in an increase in the steady state level of Rb mRNA in the nucleus. The effect of estradiol was inhibited by 10(-7) M 4-hydroxytamoxifen. In the absence of estradiol, the antiestrogens 4-hydroxytamoxifen and ICI 164,384 increased Rb mRNA by 50% over that in estrogen-depleted conditions. Estradiol regulation of Rb mRNA also occurred in other estrogen-dependent breast cancer cell lines. Insulin-like growth factor I, insulin, progestins, and epidermal growth factor had no effect on Rb expression. In summary, these results show that estradiol specifically regulates the expression of the Rb susceptibility gene product in hormone-dependent breast cancer by a posttranscriptional mechanism that occurs in the nucleus. The results from this study suggest that the negative regulation of Rb expression by estradiol, rather than Rb loss or mutation, may play an important role in breast carcinogenesis.

Breast Neoplasms↗
PubMed1995

Post-transplant hyperlipidemia: risk factors and response to dietary modification and gemfibrozil therapy.

A retrospective chart analysis of 200 consecutive, cyclosporine-treated, renal allograft recipients, transplanted between January 1988 and June 1992, was conducted to determine the incidence of and the etiologic variables for post-transplant hypercholesterolemia. In addition, the effectiveness of dietary intervention alone or in combination with gemfibrozil (600 mg b.i.d.), in post-transplant hypercholesterolemia was evaluated. Hypercholesterolemia (> or = 240 mg/dl on two separate determinations, while on maintenance immunosuppression) was present in 138 patients (Group A-69%). When compared to the remaining 62 patients without hypercholesterolemia (Group B-31%), there were no differences in mean age, body weight at transplantation, race, incidence of overt diabetes, systolic and diastolic blood pressure, or serial serum creatinine, albumin, and cyclosporine levels between these groups. Post-transplant hypercholesterolemia was significantly more prevalent in females, in recipients with higher baseline serum total cholesterol levels (mean +/- SEM, Group A = 229.0 +/- 5.0 vs. Group B = 192.0 +/- 6.1 mg/dl, p < 0.001), and in recipients with an elevated fasting blood glucose at 1 year post-transplant (Group A = 150.5 +/- 10.5 vs. Group B = 105.2 +/- 10.7 mg/dl, p < 0.05). In all patients with hypercholesterolemia, a hypocaloric low fat and low cholesterol (< 300 mg/day) diet was initiated at a mean of 0.59 +/- 0.06 years after transplantation with grading of dietary compliance at each follow-up visit (Grade 1, < 300 mg cholesterol; Grade 2, 300-500 mg cholesterol; Grade 3, > 500 mg cholesterol intake in 24 hours).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Studies on a novel anterior cruciate ligament polyethylene fiber prosthesis: the histomorphological pattern of organization and bony anchorage of a polyethylene fiber prosthesis in the stifle of the goat.

The anterior cruciate ligament of goats was substituted by a high-tensile polyethylene fiber prosthesis. The animals were sacrificed after 6-12 months. Histologically, the implants were separated from a newly formed bony shell by a thick fibrous interface membrane, which was anchored to the bone by Sharpey-like fibers. Within the joint cavity, the implants were enclosed in thick fibrous sheaths, which were continuous with the intra-osseous interface membranes. While the inner granulomatous layer of the interface membrane extended in between the polyethylene fibrils for a short distance, the bulk of the prosthesis was poorly organized. A thick central fibrous band accompanied the intra-osseous and intra-articular portions of the implants throughout their entire lengths. Oblique fibrous tracks linked the interface membranes with the central fibrous bands. The intra-osseous tunnels were considerably expanded when compared to the initially drilled tunnels.

Animals↗
PubMed1993

OKT3 rescue for steroid-resistant rejection in adult liver transplantation.

The results of OKT3 use for steroid-resistant rejection rescue in adult liver transplantation were analyzed retrospectively from a single transplant center. Comparison was made with concurrent patients who had no rejection (NR) or steroid-responsive rejections (SR). The records of 290 patients who underwent 323 liver transplants from April 1985 to December 1989 were examined. The first technically successful grafts were used for this analysis (265 grafts). Follow-up was a minimum of 1 year, or until death or loss of graft. All patients received triple-drug induction immunosuppression (CsA, Aza, steroids). Initial rejection was treated with 1 g methylprednisolone bolus i.v., followed by a 5-day taper of steroids from 200 mg to 20 mg. No rejection occurred in 108 (40.8%) and SR in 86 (32.4%), and OKT3 was given for persistent rejection in 71 (26.8%). The age, sex distribution, mean follow-up, and preoperative status were similar in all three groups. The preoperative diagnoses were similar, except for fulminant liver failure, in which 19 of 20 patients experienced rejection (P < 0.0001). The median hospitalization stay was 37 days for OKT3, 27 days for SR, and 21 days for NR (P < 0.0001). The median ICU stay was similar in the three groups (OKT3, 4; SR, 4; NR, 3). Infections in the first 6 weeks, and in the period of 6 weeks to 1 year posttransplant, were of similar frequency for all three groups. By the Kaplan-Meier estimation, the graft and patient actuarial survival rates were comparable. At 1 year, the graft survival rate was 79.6% for NR, 79.8% for SR, and 67.6% for OKT3. The 1-year patient survival rate was 85.2% for NR, 83.7% for SR, and 84.5% for OKT3. Following treatment by OKT3, rejection was permanently reversed in 42 patients. A temporary response occurred in 12 patients, 16 patients failed to respond to OKT3, 2 patients died during therapy, and 6 of the nonresponders died within 12 months. Additional OKT3 treatment was attempted in 6 patients for persistent rejection within a 1-month interval from the previous OKT3 course. Of these 6, 4 developed lymphoproliferative disorder, and only 1 survived in response to drastic reduction of immunosuppression. In conclusion, OKT3 was effective as rescue therapy for adult liver transplant steroid-resistant rejection. Because of the associated morbidity and expense, OKT3 should be used in a selective fashion. Failure to respond to OKT3 is a serious complication, and should not be managed by prolonged or repeated courses, but rather by alternative means.

Adult↗
PubMed1993

The effect of FK506 on canine bile flow.

While the primary immunosuppressive agents utilized in solid-organ transplantation are steroids and cyclosporine, the more recently introduced agent FK506 is assuming a progressively more important role as an immunosuppressant, particularly in liver transplantation. While the effect of cyclosporine on rat and canine bile flow has been well evaluated, no information is available regarding the effect of FK506 on bile flow. Dogs with chronic biliary fistulas were utilized, enabling unanesthetized animals to be studied. FK506 was administered intravenously in varying doses, and bile volume, bile salts, and bile electrolytes were measured. FK506 produced dose-related increases in bile volume and bile chloride concentration and output, with 8 micrograms/kg-1hr-1 being the maximal dose. To ascertain that the response was not osmotic in association with FK506 secretion in bile, 500 micrograms/kg-1hr-1 FK506 was administered, which did not produce a choleresis significantly greater than 8 micrograms/kg-1hr-1. FK506 was subsequently administered orally in daily dose of 0.15 mg/kg-1 for two weeks. Oral FK506 did not consistently increase bile flow, as evaluated by a bile salt dose-response curve (9, 18, 36 mumol/min sodium taurocholate) but did significantly increase bile chloride secretion. Two weeks of oral administration of FK506 in therapeutic doses did not significantly alter serum bile salt concentrations. The results of this study indicate that intravenous FK506 produces a chloride-rich choleresis in dogs.

Animals↗
PubMed1993

Cytokine-mediated regulation of rat ovarian function: interleukin-1 stimulates the accumulation of a 92-kilodalton gelatinase.

It is known that the mammalian ovary possesses a complete interleukin-1 (IL-1) system replete with ligands, receptors, and a receptor antagonist. To further assess the hypothesis that IL-1 may play an intermediary role in gonadotropin-triggered ovulation, we have set out to determine whether IL-1 is capable of promoting ovarian collagenase biosynthesis, an established component of the ovulatory cascade. Untreated cultured whole ovarian dispersates from immature (25 day old) rats constitutively elaborated several collagenolytic species as assessed in a gelatin matrix. A major 72 kilodalton (kDa) gelatinase (GL) was particularly apparent. Treatment with IL-1 beta produced selective dose- and cell density-dependent increments in the accumulation of a 92-kDa GL species. Administration of an IL-1 receptor antagonist neutralized the IL-1-induced stimulation of the 92-kDa GL in a dose-dependent fashion thereby supporting the presumption that the IL-1 effect is receptor mediated. Studies of comparable cellular densities of granulosa or enriched theca-interstitial cultures demonstrated the IL-1 induced 92-kDa GL to be highly expressed in the enriched theca-interstitial but not in the isolated granulosa cell preparations. Treatment with transforming growth factor-beta 1, a putative regulator of IL-1 action, significantly attenuated IL-1-induced 92-kDa GL accumulation thereby suggesting a potential regulatory paracrine/autocrine role for this agent in ovarian gelatinase economy. Initial characterization revealed the 92-kDa GL species to be a metalloproteinase present in its proenzyme zymogenic form. Taken together, our present findings reveal the ovarian expression of a constitutive 72-kDa GL and of an IL-1-stimulated 92-kDa GL the accumulation of which is particularly marked in enriched theca-interstitial preparations. These observations, along with the demonstration of the gonadotropin-dependent preovulatory induction of ovarian IL-1 gene expression, provide strong indirect support for the view that IL-1 may be the centerpiece of an intraovarian regulatory loop concerned with the promotion of the ovulatory cascade.

Animals↗
PubMed1993

High levels of human chorionic gonadotropin retard first trimester trophoblast invasion in vitro by decreasing urokinase plasminogen activator and collagenase activities.

Trophoblast cells of the blastocyst and of the first trimester placenta penetrate the endometrial basement membrane during the process of implantation and placental development. However, this invasive capacity seems to be restricted to the fetomaternal interface, as few trophoblast cells can be identified in the decidua, and trophoblasts rarely penetrate the maternal blood vessels. We have shown that the high invasive ability of first trimester human trophoblasts in vitro depends on collagenase activated by plasmin generation. In our study we used invasive first trimester trophoblast cells in conjunction with as in vitro amnion invasion assay to assess the role of hCG in the invasive process. hCG inhibited trophoblast invasion capacity in a dose-dependent fashion but exerted no effect on the ability of the trophoblasts to attach to the basement membrane. The activity of collagenase by trophoblasts (determined by zymography) was down-regulated by hCG, again in a dose-dependent manner. In contrast, hCG had no effect on production of the tissue inhibitor of metalloproteinases. Similar inhibitory effects of hCG on urokinase-plasminogen activator (uPA) and the activity of trophoblast-conditioned media were shown (measured by degradation of S-2444). The hCG effect on collagenase production was not mediated by the expression of procollagenase messenger RNA (mRNA), the expression of the mRNA encoding tissue inhibitor of metalloproteinase, or the expression of uPA mRNA, suggesting posttranscriptional control of hCG action. High levels of hCG attenuated the activity of commercial uPA but had no effect on commercial collagenase activity. These observations suggest that hCG may play a role in the trophoblast invasion process by inhibition of uPA activity, in turn decreasing collagenase activity and thereby reducing trophoblast cell invasion.

Cell Adhesion↗
PubMed1993

[Human protothecosis and environment].

Protothecosis are uncommon infections caused by Prototheca, considered to be achlorophylous algae. Nearly 80 human cases are reported in the literature since the first case described by Davies and Wakelin in 1964 in Sierra Leone (11). The disease have been identified in Europe, Asia (Japan, Thailand, China), Oceania and in the United States with 40 cases, particularly in the Southeast. Clinically, three clinical manifestations can be observed: 1) cutaneous lesions: papules, plaques or eczematoid, papulo-nodular areas of the extremities, 2) olecranon bursitis which occurred in 25% of cases, 3) systemic protothecosis. An immunosuppressive factor local or general can be found in half of the cases and the first description of algal meningitis was reported in a patient with AIDS in association with Cryptococcus neoformans. Because the disease is clinically not suspected, the diagnosis is often provided by histology showing a dermic granuloma with endospores. The characteristic feature of protothecosis in tissues is the presence of specific mature sporangia of Prototheca wickerhamii with the pattern of morula. The organism was PAS, Grocott and mucicarmin positive. The ecology was studied by Clark (7), Pidoux (23), Pore (25) and Sudman (27). Prototheca are ubiquitous inhabitants of sewages and are found in slime flux and animal wastes contaminating different aquatic systems. The transmission generally occurred by traumatic inoculation. Prototheca are also found in the digestive system of man and animals without never invasion of the epithelium and mucosae in experimental models. The pathogenicity and virulence are moderate and they are considered as rare opportunistic agents.

Animals↗
PubMed1993

Southern-blot analysis and simultaneous in situ detection of hepatitis B virus-associated DNA and antigens in patients with end-stage liver disease.

To gain new insights into the pathogenesis of hepatitis B virus-induced chronic liver disease, we have used nonisotopic in situ detection methods for the simultaneous analysis of hepatitis B virus DNA and antigens at the single-cell level. Paraffin-embedded liver specimens from 23 cirrhotic patients (12 HBsAg positive and 11 HBsAg negative) who underwent liver transplantation were evaluated by in situ hybridization with a digoxigenin-labeled DNA probe and digoxigenin detection system and by immunohistochemistry with an enhanced biotin-streptavidin technique. DNAs extracted from liver and serum specimens were analyzed by Southern- and slot-blot hybridization, respectively. Using the in situ techniques, we detected hepatitis B virus-specific DNA and antigens in 11 of 12 HBsAg-positive patients and in none of the 11 HBsAg-negative individuals. Replicative intermediates of hepatitis B virus DNA were detected by Southern-blot analysis in the same 11 HBsAg-positive patients, 6 of whom had no serological markers of hepatitis B virus replication. Therefore a good correlation was found between the results obtained by the in situ and Southern-blot hybridization analyses of tissue specimens. However, a lack of correlation was found between serum- and tissue-associated markers of viral replication. In addition, the simultaneous in situ detection analyses revealed that some hepatocytes containing high levels of viral DNA were devoid of detectable HBcAg, suggesting a mechanism by which the virus may escape immunological surveillance.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Southern↗
PubMed1993

Technetium-99m-labeled hydrazino nicotinamide derivatized chemotactic peptide analogs for imaging focal sites of bacterial infection.

We synthesized and evaluated four hydrazino nicotinamide (HYNIC) derivatized chemotactic peptide analogs: For-NleLFK-HYNIC (HP1), For-MLFK-HYNIC (HP2), For-MLFNH(CH2)6NH-HYNIC (HP3), and For-MLF-(D)-K-HYNIC (HP4), for in vitro bioactivity and receptor binding. The peptides were radiolabeled with 99mTc via a glucoheptonate co-ligand and their biodistribution determined in rats (n = 6/time point) at 5, 30, 60 and 120 min after injection. Localization of the peptides at sites of deep thigh Escherichia coli infection was determined by radioactivity measurements on excised tissues in rats (n = 6/time point) and rabbits as well as scintillation camera imaging in rabbits (n = 6). All peptides maintained biological activity (EC50s for O2 production by human PMNs: 12-500 nM) and the ability to bind to the oligopeptide chemoattractant receptor on human PMNs (EC50s for binding: 0.12-40 nM). After incubation with 99mTc-glucoheptonate, radiolabeled peptides were isolated by HPLC at specific activities of > 10,000 mCi/microM. Technetium-99m-labeled peptides retained receptor binding with EC50s < 10 nM. Blood clearance of all four peptides was rapid. Biodistributions of the individual peptides were similar, with low levels of accumulation in most normal tissues. In rats, all of the peptides concentrated at the infection sites (T/B ratio: 2.5-3:1) within 1 hr of injection. In rabbits, outstanding images of the infection sites were obtained, with T/B ratios of > 20:1 at 15 hr after injection. This study demonstrates that 99mTc-labeled chemotactic peptide analogs are effective agents for the external imaging of focal sites of infection.

Animals↗
PubMed1993

Biliary cystadenoma: a case report and review of the literature.

Biliary cystadenoma is a rare benign neoplasm usually found in the parenchyma of the right lobe of the liver. The lesions are usually septated and represent less than 5 percent of non-parasitic cysts of biliary origin. Malignant degeneration to biliary cystadenocarcinoma is well documented, and recurrence is the rule following incomplete excision.

Adenoma, Bile Duct↗
PubMed1993

In vivo bioactivity and biodistribution of chemotactic peptide analogs in nonhuman primates.

The dose dependence of the effect of chemotactic peptide on peripheral leukocyte levels was measured in normal Rhesus monkeys. A 99mTc-labeled hydrazino nicotinamide (HYNIC) derivatized chemotactic peptide analog was used to study biodistribution and inflammation imaging in Rhesus monkeys. In normal animals the studies demonstrated that chemotactic peptide induced a clear dose-dependent reduction in peripheral leukocyte levels. The decrease in leukocyte number occurred almost immediately after injection and rapidly returned to baseline. Significant effects on differential WBC count, blood pressure, pulse rate or respiration rate were not detected. The lowest dose of peptide tested (10 ng/kg) had minimal effect on leukocyte level. The HYNIC derivatized peptide was prepared in excellent yield and purity, had biological activity similar to the native peptide and was readily labeled at specific activity of > 20,000 mCi/mumole. When approximately 0.5 mCi (< 2.0 ng/kg) of radiolabeled peptide was injected in monkeys with focal sites of mild sterile inflammation, a pattern of biodistribution similar to radiolabeled WBCs was observed and reductions in leukocyte levels were not detected. At 3 hr after injection, the site of inflammation was readily apparent with a target-to-background ratio of approximately 3:1. These studies demonstrate that radiolabeled chemotactic peptide analogs are effective agents for imaging sites of inflammation in monkeys. By radiolabeling at high specific activity, the effect of these reagents on peripheral leukocyte levels can be avoided.

Animals↗
PubMed1993

Beneficial effects of HLA-DR3 gene expression on renal allograft survival in black recipients.

We have shown that there is a subgroup of black recipients who lack DR3 antigen expression and have decreased graft survival in comparison to black recipients who express DR3 antigen. Overall, the 3-year renal graft survival was equivalent between white and black recipients in our series and white recipients were not affected by DR3 antigen expression. We suspect that altered immune activity in the DR3-positive black patients may afford a benefit in overcoming immunologic barriers. This needs further investigation both in light of the possible association of the linked antigens A1-Cw7-B8-DR3 which are associated with loss of suppressor cell activity, as well as the issue of DR3 subtyping. However, there clearly exists the possibility of targeting higher risk groups such as the DR3-negative black recipients for more intense immunosuppressive regimens as well as eliminating pretransplant transfusion of third-party donors. Finally, we must reconsider the question of whether HLA matching is especially punitive to blacks, since matching for broad DR specificities in black recipients does not necessarily match for subtypes unique to blacks. Modifying or de-emphasizing the UNOS point system for organ allocation based on MHC antigen should be seriously considered as a mechanism for increasing the percentage of black kidney transplant recipients.

Adult↗