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Biomedical subjects

M Rubin

Publications and source records attributed to M Rubin.

At least 73 records · Page 4Linked to original sources
PubMed1997

Basic fibroblast growth factor causes growth arrest in MCF-7 human breast cancer cells while inducing both mitogenic and inhibitory G1 events.

Basic fibroblast growth factor (bFGF), a classical mitogen in fibroblasts and endothelial cells, inhibits the proliferation of MCF-7 and other human breast cancer cell lines. To explain this paradoxic effect, we investigated the effects of bFGF on cyclins and protein members of cyclin complexes that exert positive and negative control on the progression of cells through the G1 phase of the cell cycle. bFGF induced an increase in cyclin D1, cyclin E, and cyclin-dependent kinase 4 (cdk4) protein levels in a bFGF dose-dependent manner. However, bFGF also induced a heat-stable, transferable cytoplasmic factor in MCF-7 cells that inhibited the histone H1 kinase activity of reconstituted cyclin E-cdk2 and cyclin A-cdk2 complexes from Mv1Lu mink lung epithelial cells. The appearance of this inhibitor correlated with a bFGF dose- and time-dependent increase in the levels of cdk inhibitor p21(WAF1/CIP1) mRNA and protein. The increase in the level of p21(WAF1/CIP1) was associated with the disappearance of the rapidly migrating, activated form of cdk2 from cell lysates, dephosphorylation of the retinoblastoma protein (Rb), and a decrease in cyclin A levels. These changes were represented in the cyclin D1 and E complexes by an increased association with p21(WAF1/CIP1), proliferating cell nuclear antigen (PCNA), and the inactive form of cdk2, without an absolute change in cellular PCNA levels and by a switch in the association of cyclin D1 complexes with the hyperphosphorylated form to the dephosphorylated form of Rb. These experiments demonstrate that stimulation of MCF-7 cells with bFGF, although resulting in up-regulation of G1 proteins responsible for mitogenic events, also induces a concomitant decrease in cyclin A levels and an increase in p21(WAF1/CIP1) mRNA and protein and results in inactivation of cdk2, dephosphorylation of Rb, and a segregation of PCNA to the G1 cyclin complexes. The dual, conflicting signaling by bFGF results in a net inhibitory phenotype in these cells. These experiments suggest a pleiotropic role for bFGF in breast cancer.

Blotting, Western↗
PubMed1997

Hemiparetic acute myopathy of intensive care progressing to triplegia.

OBJECTIVE: To describe a unique case of acute asymmetrical myopathy following high-dose intravenous use of corticosteroids that initially mimicked a stroke and then evolved into a picture suggestive of myelopathy. DESIGN: Case report. SETTING: Tertiary hospital. PATIENTS: A 71-year-old woman treated with high-dose steroids for an acute asthmatic exacerbation developed acute hemiparesis that progressed to triplegia without evidence of central nervous system involvement. RESULTS: Nerve conduction studies, electromyography, and muscle biopsy revealed the typical features of necrotizing myopathy with loss of thick filaments. CONCLUSIONS: This case demonstrates that high-dose corticosteroid therapy can induce asymmetrical myopathic weakness. Hemiplegia evolving to triplegia in a setting of corticosteroid treatment could potentially misdirect the diagnosis toward a lesion of the brain or spinal cord. When a central nervous system abnormality cannot be demonstrated a search for a peripheral abnormality, such as myopathy, is warranted.

Adrenal Cortex Hormones↗
PubMed1997

Biosynthesis of medium-chain triacylglycerols and phospholipids by HepG-2 cells.

In an attempt to understand the metabolism by the liver of fatty acids (FA) of different chain length, we have studied the incorporation of [1(-14)C]-labeled C2, C8, C10, C12, and C16 into cellular lipids by HepG-2 cells. Over 90% of the radiolabeled FA were detected in phospholipids (PL) and triacylglycerols (TAG). The incorporation of C12 and C16 was three to four times higher than that of C8 and C10 (and reached 35 nmoles per mg protein after 1.5 h). The radioactivity of C2, C8, and C10 was recovered mainly in PL. C12 and C16 were incorporated at approximately equal amounts into PL and TAG. The radioactivity of both C2 and C8 was recovered exclusively in long-chain FA, suggesting oxidation of C8 into C2 units prior to FA synthesis. C10 likewise yielded mainly long-chain FA. However 10% of unchanged C10 was found in PL and up to 30% in TAG. 14C-C12 was largely incorporated unchanged. Under these conditions, the presence of C10 and C12 in PL and TAG was shown also by gas-liquid chromatography. In the presence of either C2, C8, or C10, up to 30% of 14C-monounsaturated FA were detected in PL and TAG. With C12 and C16, the fraction of 14C-monounsaturated FA was much smaller suggesting that extensive desaturation occurred during de novo synthesis.

Caprylates↗
PubMed1997

Use of fine needle aspiration for solid breast lesions is accurate and cost-effective.

BACKGROUND: Palpable breast tumors have traditionally been diagnosed with open biopsy or core biopsy. We propose fine needle aspiration biopsy (FNA) as a reliable, cost-saving initial procedure in these patients. METHODS: Eighty-five palpable solid breast masses of the breast in 85 patients were classified by a combination of physical examination, mammography, and/or ultrasound as probably benign, indeterminate, or highly suspicious for cancer. All tumors had FNA biopsies. All patients had either a confirmatory open biopsy (55) or close clinical follow-up (30) with a mean follow-up of 29 months (range 6 to 36). RESULTS: Thirty-four patients classified as clinically benign had a benign FNA biopsy. No cancers were detected in this group by either open surgical biopsy or clinical follow-up. Twenty patients were classified clinically as indeterminate. All had FNA biopsies, and 6 were either positive for cancer or suspicious for cancer. Fourteen patients had negative FNA biopsies. Five of the 6 abnormal biopsies had cancer on open biopsies. The 1 false-positive result occurred in a lactating patient. Thirty-one patients were classified clinically as highly suspicious for cancer. Twenty-three were confirmed as cancer with FNA biopsy. Eight needed open surgical biopsy to confirm cancer. All 31 patients clinically suspicious for cancer had cancer. In patients classified clinically as highly suspicious or probably benign, FNA was a reliable first diagnostic step (100% positive predictive value, 100% specificity, 87% sensitivity, and 89% negative predictive value). CONCLUSIONS: Fine needle aspiration biopsy of solid palpable breast lesions should be the diagnostic procedure of choice for those patients classified clinically as probably benign or clinically as highly suspicious for cancer. Cost analysis revealed elimination of an open biopsy in such cases would save $1,100 per patient. For highly suspicious cases, a negative fine needle aspiration should not deter an open surgical biopsy. For patients classified as indeterminate, fine needle aspiration biopsy results are not reliable enough to determine treatment.

Biopsy, Needle↗
PubMed1997

Prospective study of the features, indications, and surgical treatment in 513 consecutive patients affected by Crohn's disease.

BACKGROUND: The aim of this prospective study was to elucidate the features, indications, and surgical treatment in patients affected by complications of Crohn's disease. METHODS: Between January 1985 and July 1996, 513 consecutive patients (248 male, 265 female; mean age, 38 years) were operated on for 542 occurrences of Crohn's disease. Data were collected prospectively. RESULTS: Indications for abdominal surgery were often multiple but included failure of medical management (n = 220), obstruction (n = 94), intestinal fistula (n = 68), mass (n = 56), abdominal abscess (n = 33), hemorrhage (n = 7), and peritonitis (n = 9). Four hundred sixty-four abdominal procedures were performed, necessitating 425 intestinal resections and 97 stricture plasties. The use of stricture plasty was more common in the second half of the study (16.0% versus 7.3%, second half versus first half; p < 0.01). Perioperative complications occurred in 75 of the 464 abdominal operations (16%). There were no deaths. One hundred thirty patients (25%) required operation for perineal complications of Crohn's disease. The presence of Crohn's disease in the rectal mucosa was associated with a higher risk for permanent stomas in patients requiring operation for treatment of perianal Crohn's disease (67% versus 11%; p < 0.001). CONCLUSIONS: Patterns of surgical treatment in Crohn's disease are changing, with more emphasis on nonresectional options. The presence of rectal involvement significantly increases the need for a permanent stoma in patients with perianal Crohn's disease.

Adolescent↗
PubMed1997

Cardiac ultrasonography.

The use of cardiac ultrasonography in the emergency department currently has two primary indications: determining the presence of cardiac tamponade and determining cardiac activity in patients with apparent pulselessness. Physicians are able to recognize both conditions after appropriate, but not overextensive, training sessions. The evaluation of penetrating trauma, acute myocardial infarction, and severe shock of uncertain origin require a higher degree of training and experience. All of these conditions are discussed in this article.

Echocardiography↗
PubMed1997

Proximal neuropathy in Colles' fracture.

BACKGROUND: Peripheral nerve injury at the wrist following Colles' fracture is rare and usually located in the region of the fracture. Mononeuropathies in the proximal forearm have not been reported. METHOD: We present two patients with Colles' fracture with proximal forearm neuropathies. RESULTS: Both cases were associated with mononeuropathies in the forearm as proximal as the elbow, involving the median, ulnar and radial nerves in one, and the median and ulnar nerves in the other. CONCLUSION: Following Colles' fracture proximal nerve involvement may occur and, with increased awareness, this lesion may be identified more frequently.

Accidental Falls↗
PubMed1997

The use of commercially available lipid emulsions for the preparation of amphotericin B-lipid admixtures.

The use of Intralipid as a dilution medium for Fungizone, previously proposed by several groups to reduce the toxicity of amphotericin B, is limited by the instability of amphotericin B-lipid admixtures. We have shown that Fungizone-lipid admixtures with three different lipid emulsions can be stabilized by vigorous agitation. Unlike in preparations made by gentle shaking, in stable emulsions made by agitation for 18 h, most of the amphotericin B remains associated with the lipid phase for at least 1 month at 4 degrees C. The MICs of all the admixtures against various Candida spp. were similar to that of Fungizone and did not change following storage for at least 2 weeks at 4 degrees C. Furthermore, the toxicity of the admixtures, as evaluated by their haemolytic activity and amphotericin B-induced K+-leakage from human red blood cells, was much lower than that of Fungizone. Hence, amphotericin B-containing lipid emulsions made by extended agitation may be advantageous in clinical practice as they are efficient, stable, non-toxic and can be easily produced at low cost from commercially available ingredients approved for clinical use.

Amphotericin B↗
PubMed1997

Apocrine adenocarcinoma presenting as a large ulcerated axillary mass.

BACKGROUND: Apocrine adenocarcinomas are one of the rarest cutaneous cancers with few reported cases. Previously regarded nonspecifically as sweat gland tumors variants, they are now established as apocrine derivatives. Most occur in the axilla. OBJECTIVE: To provide a gross and histological description of an apocrine adenocarcinoma presenting in a 49-year-old African-American man. METHODS: The mass was removed en bloc with axillary lymph node dissection. The specimens were routinely embedded, and sectioned. Hematoxylin & eosin and periodic acid Schiff staining was done. Ploidy evaluation was performed by cytometry. RESULTS: The mass was firm, nontender, and mobile (15 x 14 x 7 cm) with overlying areas of ulcerated skin. It was closely associated with the axillary vessels, and latissimus dorsi and pectoralis major muscles, but was well circumscribed with extensive dystrophic calcification. Histological examination revealed an adenocarcinoma with predominant apocrine features. The tumor was arranged in solid sheets and large glands in the reticular dermis and had a loose trabecular pattern extending to the ulcerated skin surface. Two of seven local lymph nodes were positive for tumor; level two and three nodes were negative for tumor. DNA ploidy study determined the tumor to be an aneuploid cell line with an 18% S-phase fraction. CONCLUSIONS: Tumor growth in this patient was rapid, histology unfavorable, and local nodes positive. However, aggressive surgical intervention resulted in 12 months follow-up without evidence of recurrence.

Adenocarcinoma↗
PubMed1996

Lamivudine plus zidovudine compared with zalcitabine plus zidovudine in patients with HIV infection. A randomized, double-blind, placebo-controlled trial. North American HIV Working Party.

OBJECTIVE: To compare the safety and activity of lamivudine plus zidovudine with the safety and activity of zalcitabine plus zidovudine in patients with moderately advanced human immunodeficiency virus (HIV) infection who had received zidovudine. DESIGN: A multicenter, randomized, double-blind, three-arm, 24-week study with a blinded extension through at least 52 weeks. SETTING: 21 sites in the United States, Canada, and Puerto Rico. PATIENTS: 254 patients who had received zidovudine (median duration of previous therapy, 20 months) and had absolute CD4+ cell counts of 100 to 300 cells/mm3. INTERVENTIONS: Patients were randomly assigned to receive one of three regimens: 150 mg of lamivudine twice daily plus 200 mg of zidovudine three times daily (low-dose lamivudine group); 300 mg of lamivudine twice daily plus 200 mg of zidovudine three times daily (high-dose lamivudine group); or 0.75 mg of zalcitabine plus 200 mg of zidovudine three times daily (zalcitabine group). MEASUREMENTS: Immunologic activity was assessed primarily by changes in absolute CD4+ cell counts; virologic activity was assessed by changes in plasma HIV RNA levels as measured by reverse transcriptase polymerase chain reaction. Safety of the treatment regimens was assessed through the reporting of adverse events. RESULTS: 78% of patients completed 24 weeks of study treatment, and 63% of patients completed 52 weeks of study treatment. Changes in absolute CD4+ cell counts were significantly better for the low-dose and the high-dose lamivudine groups than for the zalcitabine group (median changes at 52 weeks were +42.5 cells/mm3 in the low-dose lamivudine group, +23.33 cells/mm3 in the high-dose lamivudine group, and -29.58 cells/mm3 in the zalcitabine group). Suppression of plasma HIV RNA levels was similar for all groups (median changes at 52 weeks were -0.48 log10 copies/mL in the low-dose lamivudine group, -0.51 log10 copies/mL in the high-dose lamivudine group, and -0.39 log10 copies/mL in the zalcitabine group). No significant differences in safety were seen among the three regimens, although the low-dose lamivudine regimen appeared to be better tolerated than the others. CONCLUSIONS: In patients with HIV infection who had previously received zidovudine, 150 mg of lamivudine plus zidovudine resulted in greater immunologic evidence of benefit than did 0.75 mg of zalcitabine plus zidovudine and was better tolerated than 300 mg of lamivudine plus zidovudine.

Adult↗
PubMed1996

[Anterior resection for rectal carcinoma in an anemic Jehovah's Witness].

Anterior resection is accepted treatment for tumors of the middle rectum, with mortality less than 5%. Since such surgery involves blood loss, blood transfusion is regarded as essential. We report a 69-year old anemic Jehovah's Witness who had a bleeding rectal tumor but who refused blood transfusion, despite a hemoglobin level of 4.8 g/dl. Anterior resection of the tumor was successfully performed without substantial blood loss. Her hemoglobin level was 5.8 g/dl on discharge. Jehovah's Witnesses do not oppose medical treatment nor do they practice faith healing. Instead, they seek good medical care but accept only proven medical alternatives to blood transfusions. Physicians, world-wide, are now successfully performing major surgery of all types on both adult and minor Witnesses. Due to their success in the use of alternatives, over 50 hospitals in North America, Europe and Australia have established "bloodless-surgery" centers to serve not only Jehovah's Witnesses but also a growing number of other patients who wish to avoid risks associated with blood transfusion.

Adult↗
PubMed1996

Involvement of p27KIP1 in G1 arrest mediated by an anti-epidermal growth factor receptor monoclonal antibody.

Activation of the cyclin dependent kinases (CDK4/CDK6 and CDK2) is required for G1 phase progression and entry into S-phase. The activation of these kinases is regulated by checkpoints that monitor environmental and intracellular conditions. Progression into S-phase is controlled, in part, by the availability of growth factors, and we have investigated the relationship between growth factor availability and the activation of the CDK kinases. Blocking activation of epidermal growth factor (EGF) receptor tyrosine kinase with anti-EGF receptor monoclonal antibody (mAb) 225 induces G1 phase cell cycle arrest in DiFi human colon adenocarcinoma cells. When DiFi cells are treated with mAb 225 for 24 h, we observe marked decreases in the activities of CDK2 kinase and cyclin E-associated CDK kinase which are not accompanied by reduced levels of cyclin E and CDK2 proteins. However, the amount of cyclin/CDK kinase inhibitor p27KIP1 increases in the mAb-treated cells and p27KIP1 is bound to CDK2 in increasing amounts. Immunodepletion of p27KIP1 removes an inhibitory activity from lysates of mAb-treated cells: the immunodepleted and heated lysates lose the capacity to inhibit cyclin E/CDK2 activity in an in vitro assay. The results suggest that G1 arrest in the cell cycle induced by EGF receptor blockade involves p27KIP1.

Antibodies, Monoclonal↗
PubMed1996

Changes in plasma HIV-1 RNA and CD4+ lymphocyte counts and the risk of progression to AIDS. Veterans Affairs Cooperative Study Group on AIDS.

BACKGROUND: Clinical trials of antiretroviral drugs can take years to complete because the outcomes measured are progression to the acquired immunodeficiency syndrome (AIDS) or death. Trials could be accelerated by the use of end points such as changes in CD4+ lymphocyte counts and plasma levels of human immunodeficiency virus type 1 (HIV-1) RNA and beta 2-microglobulin, but there is uncertainty about whether these surrogate measures are valid predictors of disease progression. METHODS: We analyzed data from the Veterans Affairs Cooperative Study on AIDS, which compared immediate with deferred zidovudine therapy. Patients' plasma levels of HIV-1 RNA and beta 2-microglobulin were measured in stored plasma. RESULTS: Among the 129 patients in the immediate-treatment group, 34 had disease that progressed to AIDS, as compared with 57 of the 141 patients in the deferred-treatment group (P = 0.03). Progression to AIDS correlated strongly with base-line CD4+ lymphocyte counts (P = 0.001) and plasma levels of HIV-1 RNA (P < 0.001), but not with base-line levels of beta 2-microglobulin (P = 0.14). A decrease of at least 75 percent in the plasma level of HIV-1 RNA over the first six months of zidovudine therapy accounted for 59 percent of the benefit of treatment, defined as the absence of progression to AIDS (95 percent confidence interval, 13 to 112 percent). Plasma beta 2-microglobulin levels and CD4+ lymphocyte counts explained less of the effect of treatment. A 75 percent decrease in the plasma HIV-1 RNA level plus a 10 percent increase in the CD4+ lymphocyte count could explain 79 percent of the treatment effect (95 percent confidence interval, 27 to 145 percent). CONCLUSIONS: Treatment-induced changes in the plasma HIV-1 RNA level and the CD4+ lymphocyte count, taken together, are valid predictors of the clinical progression of HIV-related disease and can be used to assess the efficacy of zidovudine and possibly other antiretroviral drugs as well.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Prospective study of the incidence, timing and treatment of pouchitis in 104 consecutive patients after restorative proctocolectomy.

OBJECTIVE: To determine the incidence timing and effectiveness of treatment of symptomatic pouchitis following restorative proctocolectomy with ileal J-pouch anal anastomosis. DESIGN: A cohort analytical study. SETTING: University hospitals, a tertiary referral center; all subjects entered into the study followed up for a minimum of 12 months (mean follow-up, 40 months). PATIENTS: One hundred four consecutive patients undergoing restorative proctocolectomy with ileal J-pouch anal anastomosis for either ulcerative colitis (n = 97) or familial adenomatous polyposis (n = 7) between June 1986 and December 1994. INTERVENTIONS: Patients with symptomatic pouchitis were treated with either oral metronidazole or ciprofloxacin. OUTCOMES: Diagnosis of pouchitis was determined by clinical symptoms and confirmed with endoscopy. Response to oral antibodies was determined by resolution of symptoms. RESULTS: Fifty-two patients (50%) experience at lest 1 episode of pouchitis. The first episode of pouchitis occurred within the first 12 months after restoration of intestinal continuity in 56% of the cases. In 2 patients it occurred after 30 months. Response to antibiotic treatment was 96%. Two thirds of patients had multiple episodes. Chronic pouchitis occurred in 6 patients, necessitating pouch removal in 2. CONCLUSIONS: The incidence of pouchitis after ileal J-pouch anal anastomosis is approximately 50% with two thirds of these patients having multiple episodes. Chronic pouchitis occurs in a minority of patients. In chronic pouchitis, the risk of pouch loss is substantial.

Adenomatous Polyposis Coli↗