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Biomedical subjects

P Russo

Publications and source records attributed to P Russo.

At least 253 records · Page 14Linked to original sources
PubMed1992

Cloning, sequence and expression of a beta-tubulin-encoding gene in the homobasidiomycete Schizophyllum commune.

The beta-tubulin (beta Tub)-encoding gene (tub-2) of Schizophyllum commune is the first tubulin gene isolated, cloned and sequenced from higher filamentous fungi (homobasidiomycetes). The S. commune tub-2 gene is organized into nine exons and eight introns. The introns vary from 48 to 107 nt in length, and are distributed throughout the gene. The tub-2 exons code for a protein of 445 amino acids (aa), which shows great homology with beta Tubs of filamentous ascomycetes, plants, and animals, but less homology with yeasts. The codon usage of tub-2 from S. commune is biased, as it is in most beta Tub-encoding genes of filamentous fungi. The S. commune beta Tub shows a conserved aa sequence in the C-terminal domain, which is suggested to interact with microtubule-associated proteins in animals. In contrast, the S. commune beta Tub deviates from most known beta Tubs by having a Cys165 residue, which might be significant for the insensitivity of S. commune haploid strains to the antimicrotubule drug, benomyl. In tub-2 of different haploid strains, sequence polymorphisms occur in the 5' and 3' flanking regions. The expression of tub-2 is high in young mycelium, which has a high number of extending apical cells, but decreases with the aging of the mycelium. No significant difference in the hybridization signal intensity for the tub-2 transcripts was recorded either during intercellular nuclear migration at early mating, or in mycelia with a mutation in the B mating-type gene.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1992

A heat shock gene from Saccharomyces cerevisiae encoding a secretory glycoprotein.

We report the finding of a secretory heat shock protein, HSP150, of Saccharomyces cerevisiae, and the characterization of the gene coding for it. HSP150 is constitutively expressed, extensively O-glycosylated, and secreted efficiently to the growth medium. When cells grown at 25 degrees C were shifted to 37 degrees C, a 7-fold increase in the level of HSP150 was observed within 1 hr. The HSP150 gene encodes a primary translation product of 412 amino acids. Direct amino acid sequencing of the mature secreted protein showed that an N-terminal sequence of 18 amino acids is removed, and a KEX2 protease-specific site is cleaved to yield two subunits of 53 and 341 amino acids, which remain noncovalently associated during secretion. The larger subunit is highly repetitive, containing 11 tandem repeats of a 19-amino acid sequence. Northern blot hybridization analysis showed a substantial increase in HSP150 mRNA level after heat shock. The upstream flanking region of the gene contains several heat shock element-like sequences. Disruption of HSP150 did not lead to inviability or significant effects on growth rate, mating, or thermotolerance. However, heat-regulated antigenic homologs of HSP150 were found in divergent yeasts such as Schizosaccharomyces pombe.

Amino Acid Sequence↗
PubMed1992

High-dose chemotherapy and autologous bone marrow rescue for patients with refractory germ cell tumors. Early intervention is better tolerated.

Therapy with high-dose carboplatin plus etoposide-based chemotherapy plus autologous bone marrow rescue (AUBMR) was administered to 29 patients with advanced germ cell tumors (GCT) refractory to cisplatin-based chemotherapy. Two groups of patients with refractory disease were treated. Sixteen patients had been identified as "poor risk" at diagnosis and had an inappropriately slow decline of serum tumor markers after two cycles of induction cisplatin-based therapy (Group A). In addition, 13 patients were treated who had never had a complete response (CR) or had relapses after ifosfamide-based salvage chemotherapy (Group B). Patients in Group A were treated with high-dose carboplatin etoposide, and patients in Group B received high-dose carboplatin, etoposide, and cyclophosphamide. Fifteen of 29 (52%) patients had a CR (9, Group A; 6, Group B). The patients in Group A had fewer hematologic toxic effects, and the median number of days from day 0 to a granulocyte count greater than 0.5/microliters was 16 and to a platelet count of more than 50/microliters was 15, compared with 22 days and 23 days in Group B, respectively. There were fewer episodes of culture-positive sepsis in Group A (12%) compared with Group B (26%), and the only treatment-related death occurred in Group B. Therapy with high-dose carboplatin plus etoposide-based chemotherapy plus AUBMR is effective for patients with GCT refractory to regimens of cisplatin with or without ifosfamide. Early use of high-dose chemotherapy reduces hematologic toxic effects and allows patients to start treatment in a more predictable fashion after cytoreduction, rather than when the disease is progressing rapidly.

Adult↗
PubMed1992

Acute intermittent porphyria. A perplexing case.

We report the case of a 58-year-old woman affected by polyneuropathy, vegetative disturbances and abdominal pain. A provisional diagnosis of acute intermittent porphyria was made and was confirmed by the increased levels of urinary delta-aminolevulinic acid (ALA) and porphobilinogen (PBG).

Acute Disease↗
PubMed1992

Serum beta 2-microglobulin levels and p24 antigen, lymphocyte depletion and disease progression in human immunodeficiency virus infection.

Abnormally elevated serum beta 2-microglobulin levels have been associated with progression of human immunodeficiency virus disease. In this study we have analyzed the relationship between serum beta 2-microglobulin levels of patients at different stages of the disease and serological and immunological parameters commonly used for monitoring the infection. The investigation was performed on 150 patients and 30 controls during the period from March 1989 to March 1990. At that time, 30 patients had the acquired immunodeficiency syndrome or its related complex and 120 had persistent generalized lymphadenopathy or were asymptomatic. Thirty-nine antibody-negative subjects, belonging to a high-risk group for the acquired immunodeficiency syndrome, were used as controls. All patients had normal renal function. There was a significant relationship between increased serum beta 2-microglobulin levels and the presence of p24 antigen, a decrease in the total number of lymphocytes (less than or equal to 1500/mm3) and a decrease in CD4+ T lymphocytes (less than or equal to 200/mm3). No significant relationship between serum beta 2-microglobulin levels and CD3+ T lymphocytes was found.

Adolescent↗
PubMed1992

Successful treatment of acute postoperative pulmonary hypertension with nifedipine.

We report the successful use of nifedipine in the treatment of acute pulmonary hypertension in an infant after a cardiac operation. This patient had undergone total surgical correction of his truncus arteriosus malformation. He had signs of severe pulmonary artery hypertension unresponsive to hyperventilation, oxygenation, sedation, and a myriad of vasodilators. Nifedipine, 0.2 mg/kg every 4 hours, effectively treated his pulmonary artery hypertension and allowed for a smooth postoperative course and positive outcome.

Humans↗
PubMed1992

Identification and subcellular localization of the Q gene product of visna virus.

The genome of the sheep visna lentivirus contains an open reading frame, Q, which has a coding potential of 230 amino acid residues. This paper reports the identification and the subcellular localization of the Q ORF-encoded protein detected in lysates of visna virus-infected sheep choroid plexus cells. Sera from sheep either experimentally or naturally infected with visna virus reacted with the bacterially synthesized Q protein indicating that the in vivo expressed Q product is immunogenic. Antibodies raised against a synthetic N-terminal peptide, reacted with either the bacterial Q or the in vitro translated Q protein as well as with the Q protein expressed during cellular infection. This 29 kDa protein is detectable late in the lytic viral cycle, i.e., 72 hr postinfection, and this expression correlates with the late transcription of its 4.8-kb mRNA. These results provide evidence for the first time that the Q ORF is a late gene of visna virus and that the Q protein is located in the cytosol compartment, without evidence of accumulation at the cell membrane, or in cell-free virion particles.

Animals↗
PubMed1992

A congenital anomaly of vitamin B12 metabolism: a study of three cases.

The clinical and morphologic findings of three patients with metabolic acidosis, methylmalonic aciduria, and homocystinuria are presented. The clinical evolution of the patients was similar and was characterized in the first weeks of life by failure to thrive, hypotonia, and lethargy associated with pancytopenia and hepatic dysfunction, eventually progressing to severe respiratory insufficiency and renal failure consistent with a hemolytic-uremic syndrome. The patients died at 40, 45, and 75 days of age. Biochemical analyses and complementation studies revealed a congenital anomaly of vitamin B12 metabolism (cobalamin C disease). Postmortem morphologic findings in all three cases were dominated by a thrombotic microangiopathy of the kidneys and lungs, diffuse hepatic steatosis, and megaloblastic changes in the bone marrow. A severe gastritis with striking cystic dysplastic mucosal changes and total absence of parietal and chief cells was a consistent finding in all three cases, the rest of the gastrointestinal tract appearing essentially normal. Cobalamin C disease is an intracellular defect of cobalamin metabolism with possible recessive inheritance that can result in multiorgan failure early in life, with a thrombotic microangiopathy and unusual changes in the gastric mucosa.

Humans↗
PubMed1992

Adult urological sarcoma.

From July 1982 to December 1989, 43 of 1,583 adults (2.7%) with soft tissue sarcoma admitted to the Memorial Sloan-Kettering Cancer Center (MSKCC) had tumors arising from the urinary tract and male genital tract (urological sarcoma). The most common site of origin of the tumor was paratesticular (14 patients), followed by the prostate/seminal vesicle (12), bladder (10) and kidney (7). The most common histological type was leiomyosarcoma (19 patients), followed by rhabdomyosarcoma (14), liposarcoma (5) and 5 other histological sarcoma categories (angiosarcoma, malignant fibrous histiocytoma, mesenchymoma and 2 undifferentiated sarcomas). Most of the tumors were high grade (86%) and more than half (56%) were greater than 5 cm. in diameter. A total of 9 patients (21%) presented with metastatic disease, 8 of whom had rhabdomyosarcoma. Complete resection with negative microscopic margins was possible in 58% of the patients. Actuarial relapse-free survival for all patients at 3 and 5 years was 55% and 40%, respectively. There were no significant differences in survival based on patient age, sex or histological tumor type. Favorable prognostic variables by univariate analysis included tumor diameter less than 5 cm., low histological grade, paratesticular or bladder tumor site and complete surgical resection. Application of the MSKCC sarcoma staging system, which is based on grade, size, depth and presence or absence of metastasis, was useful to predict survival. In our experience patients with stage 3 (high grade, greater than 5 cm., 15 patients) or stage 4 (metastatic disease, 9 patients) had a combined 3-year relapse-free survival rate of only 26% and they should be considered candidates for adjuvant treatment protocols.

Actuarial Analysis↗
PubMed1992

Potentiation by tumor necrosis factor of mitoxantrone cytotoxicity to human ovarian cancer cell lines.

The cytotoxic activity of human recombinant tumor necrosis factor (rHuTNF) (from 0.01 to 10000 U/ml) was assayed on six human ovarian cancer cell lines and one human cervical carcinoma cell line using a crystal violet assay. rHuTNF was cytotoxic to four cell lines (A2780, A2774, SW626, PA1), while 3 cell lines (IGROV1, SKOV3, Me180) were marginally sensitive to its activity. However, under the same experimental conditions rHuTNF markedly enhanced the cytotoxicity of mitoxantrone, a chemotherapeutic drug targeted at DNA topoisomerase II, in six cell lines. The potentiation of mitoxantrone cytotoxicity was not caused by increased drug accumulation after rHuTNF treatment. No significant increase in cytotoxicity to Me180 cell line was seen when rHuTNF was added to mitoxantrone.

Drug Screening Assays, Antitumor↗
PubMed1992

Potentiation of topoisomerase I and II inhibitors cell killing by tumor necrosis factor: relationship to DNA strand breakage formation.

Recombinant human tumor necrosis factor (rHuTNF) synergistically potentiates the cytotoxicity of the topoisomerase I inhibitor camptothecin, and the topoisomerase II inhibitors epidoxorubicin, etoposide, mitoxantrone, ellipticine, actinomycin D and 4'-(9-acridinylamino)methanesulfon-m-anisidide on A2780 human ovarian cancer cell line. Similar synergy was not observed with a combination of rHuTNF and cis-platinum or mitomycin C. When A2780 cells were incubated with rHuTNF simultaneously with camptothecin or mitoxantrone or VP16, increased numbers of DNA single-strand breaks were produced. rHuTNF alone did not induce DNA strand breakage. These data provide evidence that the enhancing effect of rHuTNF is closely related to the DNA damage mediated by topoisomerase-targeted drugs. These observations may have relevance for ovarian cancer treatment.

Camptothecin↗
PubMed1992

The ontogeny and site of intestinal lipid and lipoprotein synthesis.

The developmental aspects of characteristic intestinal lipoprotein synthesis, chlomicrons (CM), very low density lipoproteins (VLDL) and high density lipoproteins (HDL), are unknown. Our objective was to determine the ontogeny of intestinal lipid and lipoprotein synthesis in both the jejunum and the ileum. Explants of the jejunum and the ileum from fetal (F) (18-19 days of gestation), suckling (S) (5 days old) and weaning (W) (23 days old) rats were cultured in the presence of [14C]-oleic acid to examine lipid synthesis. The results indicate the following. (1) The incorporation of oleic acid is higher for the fetal explants. However, the efficiency of esterification of free fatty acids (FFA) into triglycerides (TG) in the jejunum increases with age (33% F, 37% S, 48% W) (P less than 0.05, by ANOVA). (2) The same profile is found at the ideal site for the incorporation of oleic acid. However, the capacity for the synthesis of TG is more intense at the suckling period (34% F, 54% S, 42% W) (P less than 0.05, by ANOVA). (3) The relative content of TG in CM changes with age: F, 90-93%; S, 80-84%; W, 33-40%. (4) A low percentage of TG content is found in CM at the weaning period while high levels are detectable in VLDL (40-42%). (5) A most significant difference is noted between the jejunum and the ileum in TG synthesis at the suckling period. The ileum synthesizes 53% more TG than the jejunum (P less than 0.025). (6) HDL particles contain substantial amounts of FFA. Nevertheless, they were also found to be able to transport TG mainly in the suckling rat. Thus, this study demonstrates that with growth the rat is able to synthesize CM, VLDL and HDL. Our findings indicate changes in the synthesis of intestinal lipids and lipoproteins, depending on both the development and the site, which suggests an ontogeny. These modifications can be attributed to dietary and hormonal influences present during the period of development.

Animals↗
PubMed1992

Influence of muramyl dipeptide on renal candidiasis in genetically distinct mice.

Susceptible (DBA/2) and resistant (C57BL/6) mice were inoculated intravenously with Candida albicans to evaluate the effect of a four-day prophylaxis with muramyl dipeptide (MDP) on the renal burden of organisms during the first week after infection. In sham-treated DBA/2 mice injected with 8 x 10(4) candida cells, renal CFU (LOG10 +/- SEM) on days 1, 4 and 7 after infection were found to average 5.050 +/- 0.109, 4.882 +/- 0.133 and 5.482 +/- 0.245. In sham-treated C57BL/6 mice injected with 2 x 10(5) candida cells, renal CFU on days 1, 4 and 7 reached only 3.610 +/- 0.118, 3.404 +/- 0.107 and 4.176 +/- 0.580. MDP-treated DBA/2 mice achieved significant reduction in CFU of C. albicans on day 1 (1.3 log units) and day 4 (0.6 log unit), while MDP-treated C57BL/6 mice had significant reduction in CFU of C. albicans only on day 1 (0.6 log unit) after infection. Sham-treated mice of both strains had a 28.6 to 30% increase in kidney weights on day 4 only, a transient change not seen in MDP-treated mice. Histopathological examination on days 8, 15 and 21 after infection revealed a higher incidence of renal papillary necrosis in DBA/2 mice than C57BL/6 mice (approximately 70% vs 10%). The incidence of granulomas and of chronic interstitial inflammation was much higher in MDP-treated mice. We conclude that the genetic makeup of the host influences the potential effectiveness of MDP as a biological response modifier.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1992

Identification and initial characterization of insulin receptor-like immunoreactivity in human plasma.

With a two-step purification procedure employing sequential affinity chromatography with insulin receptor monoclonal antibody followed by wheat germ agglutinin, we isolated from the plasma of two healthy individuals a material that reacted in a specific RIA for insulin receptors. This material produced dilution curves that were parallel to a human placental insulin receptor standard. This material also bound [125I]insulin; competition-inhibition curves revealed an ED50 of 0.3 nM, a value similar to that obtained with placental insulin receptors. The material purified from plasma was then labeled with [125I] Bolton-Hunter reagent, followed by polyacrylamide gel electrophoresis under reducing conditions and autoradiography. A band at 135 kilodaltons (kDa) was observed, corresponding to the alpha-subunit of the insulin receptor. Several bands ranging from 82-46 kDa were also detected. One or more of these fragments had intrinsic autophosphorylation activity, but only the 82-kDa band activity was responsive to insulin. In addition, employing the synthetic substrate poly(Glu4:Tyr1), no insulin-sensitive tyrosine kinase activity was present. These studies demonstrate, therefore, that insulin receptor-derived material is present in human plasma. This material retains high affinity insulin binding, but has an altered beta-subunit that is devoid of insulin-responsive tyrosine kinase activity.

Humans↗
PubMed1992

[Long-term treatment of stable angina pectoris with gallopamil].

BACKGROUND: The effects of long-term treatment with gallopamil 50 mg t.i.d were assessed in 8 patients, 7 males and 1 female, aged 47-69 years, with stable angina pectoris, positive exercise tests, coronary artery disease and no previous myocardial infarction. METHODS: Clinical and ECG parameters as well as exercise testing, 24-hour Holter and echocardiography were assessed before treatment, after 3 months, after 1 and 2 years of treatment, and following final wash-out. RESULTS: Comparing each treatment period to baseline, a significant decrease in resting heart rate (from 66 +/- 9 beats/min at baseline to 56 +/- 7 beats/min after 3 months [p < 0.01], 59 +/- 8 beats/min after 1 year [p < 0.05] and 58 +/- 9 beats/min after 2 years [p < 0.05]), systolic (from 162 +/- 19 mmHg at baseline to 147 +/- 12 mmHg after 3 months [p < 0.05], 146 +/- 20 mmHg after 1 year [p < 0.01] and 146 +/- 27 mmHg after 2 years [p < 0.05]), and diastolic (from 89 +/- 6 mmHg to 82 +/- 7 after 3 months [p < 0.05], 82 +/- 4 after 1 year [p < 0.05] and 83 +/- 4 after 2 years [p < 0.05]) blood pressure was observed. Exercise time significantly improved (from 596 +/- 209 seconds to 802 +/- 66 seconds after 3 months [p < 0.01], 710 +/- 167 seconds after 1 year [p < 0.05] and 723 +/- 125 seconds after 2 year [p < 0.05]), while heart rate and rate-pressure product at peak exercise did not change. The number of ischemic episodes and the total ischemic time per 24 hours significantly decreased (from 35 +/- 15 min to 12 +/- 10 min after 3 months [p < 0.05], 10 +/- 8 min after 1 year [p < 0.05] and 11 +/- 9 min after 2 years [p < 0.05]). Ejection fraction increased (from 66 +/- 10% to 77 +/- 7% after 3 months [p < 0.01], 80 +/- 5% after 1 year [p < 0.01] and 80 +/- 3% after 2 years [p < 0.01]), while contractility, as expressed by the end-systolic stress/end systolic volume ratio remained unchanged. No serious side-effects or biochemical abnormalities developed. CONCLUSIONS: Gallopamil appears to be safe, well tolerated and effective in the long term control of angina pectoris; its effects are fully developed at 3 months and persist unchanged after 2 years. For its hypotensive action and the lack of significant effects on myocardial contractility, gallopamil appears to be potentially useful in patients with associated angina and hypertension and in patients with impaired left ventricular function.

Aged↗
PubMed1992

[Brain aging and calcium antagonist drugs. A preliminary open study with nimodipine].

Forty patients aged 65-80 with minor-medium signs of brain aging were treated for 6 months with daily 90 mg doses of nimodipine. Treatment was well tolerated in that the minor side effects reported by a few of the patients never required withdrawal of the drug. Treatment proved useful, as shown by a variety of mental tests, in 69.5% of cases. In 20% conditions remained unchanged and in 9.5% further deterioration was observed. The authors conclude that nimodipine may be considered a useful therapeutic resource for phenomena of brain aging.

Aged↗