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Biomedical subjects

E Resnik

Publications and source records attributed to E Resnik.

At least 19 recordsLinked to original sources
PubMed2001

Circadian activity of the GABAergic system in the golden hamster retina.

Daily changes in gamma-aminobutyric acid (GABA) turnover rate were studied in the golden hamster retina. This parameter showed significant variations throughout the light-dark cycle, with minimal values during the day. Retinal glutamic acid decarboxylase (GAD) activity was higher at midnight than at noon. Moreover, [3H]GABA binding significantly varied throughout the 24-h cycle, with maximal values during the day. Saturation studies performed at 12:00 and 24:00 h indicated that the maximal concentration of [3H]GABA binding sites (Bmax) was significantly higher at noon, whereas the dissociation constant (Kd) remained unchanged. High K+-induced GABA release was significantly higher at midnight than at midday. Daily variations in retinal GABA turnover rate, GABA release, and in its specific binding persisted in golden hamsters exposed to constant darkness. In summary, these results support the idea of a circadian clock-controlled GABAergic activity in the hamster retina.

Animals↗
PubMed2000

Voltage-gated K(+)-channel activity in ovine pulmonary vasculature is developmentally regulated.

To examine mechanisms underlying developmental changes in pulmonary vascular tone, we tested the hypotheses that 1) maturation-related changes in the ability of the pulmonary vasculature to respond to hypoxia are intrinsic to the pulmonary artery (PA) smooth muscle cells (SMCs); 2) voltage-gated K(+) (K(v))-channel activity increases with maturation; and 3) O(2)-sensitive Kv2.1 channel expression and message increase with maturation. To confirm that maturational differences are intrinsic to PASMCs, we used fluorescence microscopy to study the effect of acute hypoxia on cytosolic Ca(2+) concentration ([Ca(2+)](i)) in SMCs isolated from adult and fetal PAs. Although PASMCs from both fetal and adult circulations were able to sense an acute decrease in O(2) tension, acute hypoxia induced a more rapid and greater change in [Ca(2+)](i) in magnitude in PASMCs from adult compared with fetal PAs. To determine developmental changes in K(v)-channel activity, the effects of the K(+)-channel antagonist 4-aminopyridine (4-AP) were studied on fetal and adult PASMC [Ca(2+)](i). 4-AP (1 mM) caused PASMC [Ca(2+)](i) to increase by 94 +/- 22% in the fetus and 303 +/- 46% in the adult. K(v)-channel expression and mRNA levels in distal pulmonary arteries from fetal, neonatal, and adult sheep were determined through the use of immunoblotting and semiquantitative RT-PCR. Both Kv2.1-channel protein and mRNA expression in distal pulmonary vasculature increased with maturation. We conclude that there are maturation-dependent changes in PASMC O(2) sensing that may render the adult PASMCs more responsive to acute hypoxia.

4-Aminopyridine↗
PubMed1999

Hemiballismus and brain metastases from squamous cell carcinoma of the cervix.

BACKGROUND: Brain metastases from cervical carcinoma are rare. Accompanying symptoms depend on the location of the metastatic lesions. Hemiballismus refers to a rare movement disorder characterized by involuntary, large amplitude movements of the limbs of one side of the body. The area of the brain controlling the limb movement is in the subthalamic nucleus of the contralateral side. In contrast, the usual location of brain metastases from cervical cancer is in the frontal and parietal parenchyma. There have been reported cases of hemiballismus secondary to metastatic carcinoma of the breast, lung, and gall bladder. This is the first reported case of putative cervical cancer metastases associated with hemiballismus. CASE: A 38-year-old Caucasian female was diagnosed with FIGO stage II-B poorly differentiated squamous cell carcinoma of the cervix. Para-aortic lymph nodes were positive for metastatic disease. The patient was treated by radiation with hydroxyurea chemosensitization. Four months after the initial diagnosis she presented with acute onset of hemiballismus. Magnetic resonance imaging of the head revealed a solitary lesion in the left cerebral peduncle extending into the inferior aspect of the left basal ganglia complex. The lesion was inaccessible to biopsy or excision. Palliative radiation therapy to the brain was unsuccessful and the patient expired 1 year following primary presentation. CONCLUSION: Treatment of hemiballismus is directed to its underlying causes. Some brain metastases from cervical cancer may be palliated or even cured by surgical resection and radiation therapy. Although not conclusive, it appears that hemiballismus in a setting of metastatic cervical cancer has a poor prognosis and little benefit from irradiation.

Adult↗
PubMed1997

Long-term survival and DNA ploidy in advanced epithelial ovarian cancer.

BACKGROUND AND OBJECTIVES: The relationship of the tumor DNA content to survival of patients with advanced epithelial cancer has not yet been clarified. A large amount of contradictory data exists in the literature. This study analyzes the putative relationship between ploidy and advanced ovarian carcinoma. METHODS: A retrospective analysis of tumor ploidy, DNA index, and the S-phase fraction from 35 patients with nonborderline epithelial ovarian carcinomas was determined by flow cytometry of paraffin-embedded tissue. All patients had FIGO stage III or IV disease. Those patients who survived > 5 years were assigned to Group A (10 patients). Group B consisted of 25 age-matched subjects who succumbed to their disease within 5 years of diagnosis. RESULTS: Group A had not reached a median overall survival with a median follow-up of 114 months (range 67-226), whereas Group B had a median overall survival of 17 months (range 1-48). Two of the patients in Group A and all of the patients in group B had died of the disease. The two groups were similar in age, histologic type, and treatment. In Group A, three patients had grade 1 tumors, in contrast to group B where all the patients had either grade 2 or 3 disease (P = 0.018). However, the distribution of aneuploidy was similar in both groups. Also, the DNA indices were similar: 1.40 +/- 0.42 in Group A, and 1.36 +/- 0.44 in Group B. The median S-phase fraction was 14% (range 3-23%) in Group A, and 15% (range 2-23%) in Group B. The grade and type of tumor were not related to the ploidy or the DNA index. There was no significant correlation between ploidy or the DNA index and survival. CONCLUSION: This study suggests that the DNA content of tumor as measured by flow cytometry is not a predictor of long-term survival in ovarian cancer patients with advanced disease.

Adult↗
PubMed1996

Syndrome of inappropriate antidiuretic hormone secretion in papillary serous surface carcinoma of the peritoneum.

A case of syndrome of inappropriate antidiuretic hormone secretion (SIADH) in a patient with suboptimally cytoreduced stage III papillary serous surface carcinoma of the peritoneum is described. After the primary surgery, the patient refused further therapy. Within a month bilateral pleural effusions and abdominal ascites compelled the patient to accept treatment with carboplatin and cyclophosphamide. Ten days following the chemotherapy, she was admitted in a disoriented state with serum sodium of 117-mEq/L. During the evaluation, treatment, and subsequent follow-up, the diagnosis of SIADH was confirmed. Numerous disease processes have been associated with the development of SIADH; however, there have been few reports in gynecologic malignancies. Possible etiology and clinical management of this patient are briefly discussed.

Aged↗
PubMed1996

Malignant uterine smooth muscle tumors: role of etoposide, cisplatin, and doxorubicin (EPA) chemotherapy.

BACKGROUND: Nearly 80% of patients with malignant uterine smooth muscle tumor will suffer local relapse and/or distant metastases after initial surgical resection. There is no convincing evidence that the addition of pelvic radiation improves the outcome. However, adjuvant chemotherapy might be an appropriate therapeutic modality. METHODS: Between 1986 and 1991, 13 consecutive patients with malignant uterine smooth muscle tumors were treated at Yale-New Haven Hospital with a combination chemotherapy containing etoposide 100 mg/M2 on days 1 and 2, cisplatin 50 mg/M2 on day 1, and doxorubicin 50 mg/M2 on day 1, repeated every 28 days. Six patients had Stage I disease, one patient had Stage III disease, and six patients had Stage IV disease. The number of cycles ranged from 2 to 9. RESULTS: The median follow-up was 30 months (range 4-81). The mean overall survival for the group was 43.1 +/- 6.7 months, with the progression-free interval of 25.5 +/- 8.0 months. Of the seven patients with evaluable disease, one patient had complete response and one had partial response (total response rate of 28.6%). Of the six patients treated adjuvantly, three recurred at 9, 33, and 59 months (recurrence rate of 50%). CONCLUSIONS: We conclude that this combination has only modest activity against malignant uterine smooth muscle tumors at the schedule and doses tested.

Adult↗
PubMed1996

Combination chemotherapy with etoposide, cisplatin, and doxorubicin in mixed müllerian tumors of the adnexa.

Eleven patients with ovarian (9) or fallopian tube (2) mixed müllerian tumors who underwent primary surgery at Yale New Haven Medical Center between 1986 and 1994 were treated with etoposide, cisplatin, and doxorubicin. Responses were observed in three (60%) of five evaluable patients with two complete (40%) and one partial (20%) response. Median survival time was 17 months with an estimated 3-year survival of 18%. Survival may have been improved with earlier stage disease, but survival was not significantly improved with optimal surgical cytoreduction in patients with advanced disease. Four patients required dose reductions for myelosuppression and there was one treatment related death. Toxicity was comparable to other combination chemotherapy regimens. EPA has modest therapeutic activity in ovarian and fallopian tube MMT.

Aged↗
PubMed1996

Neoadjuvant chemotherapy in uterine papillary serous carcinoma.

Uterine papillary serous carcinoma (UPSC) is an aggressive variant of endometrial cancer that frequently imitates serous carcinoma of the ovary in its clinical presentation and histologic appearance. Unlike the ovarian lesion, however, it is known to be particularly resistant to chemotherapy. A patient with a putative diagnosis of unresectable Stage IV ovarian cancer was treated with three cycles of neoadjuvant chemotherapy containing paclitaxel and carboplatin. After a remarkable response, interval cytoreductive surgery was performed. A primary endometrial tumor with the pathologic features of UPSC was found. To our knowledge, the use of paclitaxel-containing chemotherapy in UPSC has not been reported. We suggest that this therapy might be useful in the treatment of patients with advanced uterine papillary serous carcinoma, as well as in an adjuvant setting.

Aged↗
PubMed1996

Integration host factor amplifies the induction of the aceBAK operon of Escherichia coli by relieving IclR repression.

A binding site for integration host factor (IHF) was identified upstream of the aceBAK promoter. Under inducing conditions, IHF activates aceB::lacZ expression by opposing IclR repression. In contrast, IHF has little effect on aceB::lacZ expression under repressing conditions. The ability of IHF to relieve repression under inducing but not repressing conditions allows this protein to amplify the induction of aceBAK.

Acetates↗
PubMed1995

A phase II study of etoposide, cisplatin, and doxorubicin chemotherapy in mixed müllerian tumors (MMT) of the uterus.

Mixed Müllerian tumors (MMT) of the uterus are aggressive entities that result in a very poor prognosis even for patients in whom the disease is limited to the uterus. This phase II trial was undertaken in an attempt to improve overall survival as well as progression-free survival of these patients. Forty-two consecutive patients were treated with a combination chemotherapy containing etoposide 100 mg/m2 on Days 1 and 2, cisplatin 50 mg/m2 on Day 1, and doxorubicin 50 mg/m2 on Day 1, repeated every 28 days. There were 23 patients with early-stage disease (stages I and II) and 19 patients with advanced (stages III and IV) or recurrent disease. In the early-stage group, the number of cycles ranged from 2 to 9 (5.2 +/- 1.9). The median follow-up was 32 months (range 11-93). There were five recurrences: three patients died of disease at 11, 36, and 51 months, and two patients are still alive with disease at 12 and 19 months. Two-year overall survival was 92%. In the advanced disease group, the number of cycles ranged from 1 to 11 (5.9 +/- 2.4). The median follow-up for this group was 20 months (range 5-62). The median overall survival was 18 months. Two-year overall survival was 33%. Two-year progression-free survival was 20%. Four patients were evaluable for response. There were two complete responses (duration 15-33 months) and two partial responses (duration 6-10 months). The responders were patients whose adenocarcinoma component was of the papillary serous (UPSC) variety. The chemotherapy combination appears to be highly active in early-stage disease. In the advanced uterine MMT it has moderate activity, especially when associated with the UPSC component.

Aged↗
PubMed1994

Engineering the quaternary structure of an enzyme: construction and analysis of a monomeric form of malate dehydrogenase from Escherichia coli.

The citric acid cycle enzyme, malate dehydrogenase (MDH), is a dimer of identical subunits. In the crystal structures of 2 prokaryotic and 2 eukaryotic forms, the subunit interface is conformationally homologous. To determine whether or not the quaternary structure of MDH is linked to the catalytic activity, mutant forms of the enzyme from Escherichia coli have been constructed. Utilizing the high-resolution structure of E. coli MDH, the dimer interface was analyzed critically for side chains that were spatially constricted and needed for electrostatic interactions. Two such residues were found, D45 and S226. At their nearest point in the homodimer, they are in different subunits, hydrogen bond across the interface, and do not interact with any catalytic residues. Each residue was mutated to a tyrosine, which should disrupt the interface because of its large size. All mutants were cloned and purified to homogeneity from an mdh- E. coli strain (BHB111). Gel filtration of the mutants show that D45Y and D45Y/S226Y are both monomers, whereas the S226Y mutant remains a dimer. The monomeric D45Y and D45Y/S226Y mutants have 14,000- and 17,500-fold less specific activity, respectively, than the native enzyme. The dimeric S226Y has only 1.4-fold less specific activity. All forms crystallized, indicating they were not random coils. Data have been collected to 2.8 A resolution for the D45Y mutant. The mutant is not isomorphous with the native protein and work is underway to solve the structure by molecular replacement.

Amino Acid Sequence↗
PubMed1994

Early postpartum endometritis. Randomized comparison of ampicillin/sulbactam vs. ampicillin, gentamicin and clindamycin.

Seventy-six parturients with a clinical diagnosis of early postpartum endometritis were randomized to be treated with either standard therapy--ampicillin, gentamicin and clindamycin--or a new regimen, ampicillin/sulbactam. We deliberately chose to administer 1.5 g of ampicillin/sulbactam rather than a 3-g dose every six hours in order to accentuate any differences that might occur between the regimens. Failure rates, days of therapy and cost of treatment were compared. There was no statistically significant difference (P > .9) in the failure or recovery rates: 4 of 42 (9.5%) patients failed standard therapy vs. 6 of 34 (17.6%) patients in the ampicillin/sulbactam group. The times to recovery were 3.6 +/- 1.8 SD and 3.3 +/- 1.3 days, respectively. There was no difference in side effects or drug toxicity between the two groups. The cost of standard therapy was $355.32 for 3.6 days, whereas ampicillin/sulbactam cost $139.49 for 3.3 days. Therapy with ampicillin/sulbactam may be an equally effective and efficient way to treat patients with early postpartum endometritis.

Adult↗
PubMed1993

Advanced ovarian carcinoma: molecular evidence of unifocal origin.

The clonal origin has sometimes been disputed in advanced epithelial cancers when multiple sites of peritoneal tumors were present because of the developmental similarity of the surface epithelium of the ovary and the peritoneal mesothelium. We have taken two independent approaches to study the clonality of advanced epithelial carcinoma. Tumor samples of both ovaries, and/or omentum, and/or peritoneum from nine patients were examined. The analysis of loss of heterozygosity (LOH) at 86 polymorphic chromosomal loci distributed on every chromosome revealed the loss of the same allele in every tumor of each patient when LOH was detected. In addition, we used a restriction-fragment-length polymorphism in an X-linked sequence (DXS255) to examine the pattern of X-chromosome inactivation based on the differential methylation of DXS255 in active and inactive X chromosomes. Inactivation of the same X chromosome in various tumors from the same patient was observed in each of the five informative patients. Our results strongly suggest that the advanced epithelial cancers are monoclonal in origin.

Adult↗
PubMed1993

Relative expression of the products of glyoxylate bypass operon: contributions of transcription and translation.

Although the genes of the aceBAK operon are expressed from the same promoter, the relative cellular levels of their products are approximately 0.3:1:0.003. Gene and operon fusions with lacZ were constructed to characterize this differential expression. The upshift in expression between aceB and aceA resulted from differences in translational efficiency. In contrast, inefficient translation and premature transcriptional termination contributed to the downshift in expression between aceA and aceK. Premature transcriptional termination occurred within aceK and appears to result from inefficient translation. Deletion of repetitive extragenic palindromic elements between aceA and aceK had little effect on the relative expression of these genes. Rather, the sequences responsible for inefficient expression of aceK lie within the aceK ribosome binding site.

Base Sequence↗
PubMed1992

Inhibition of interferon gamma production by peripheral blood mononuclear leukocytes of patients with sarcoidosis. Pathogenic implications.

Interferon gamma (IFN-gamma) production by stimulated peripheral mononuclear leukocytes of 30 patients with sarcoidosis was studied. A significant inhibition (64 percent, 5 to 330 IU/ml vs normal individuals = 1,000 +/- 250 IU/ml) in the IFN-gamma synthesis was found. The inhibition is due to a defect in the circulating monocytes and not in the peripheral T lymphocytes of these patients. This defect in the peripheral IFN-gamma production could be involved in the pathogenesis of this disease.

Biological Assay↗
PubMed1992

Transvesical cesarean following bowel and urinary tract reconstructive surgery.

Intentional transvesical cesarean was done for delivery in a woman born with an imperforate anus, ectopic intravaginal urethra, and vaginal and urethral strictures. She had undergone multiple reconstructive procedures that left her bladder completely covering the anterior uterine surface. The rest of the uterus, including the fundus and the broad ligaments, was obscured by multiple bowel adhesions. Cesarean delivery was necessary because of pelvic bone and soft-tissue deformity. Anterior and posterior vertical cystotomies resulted in exposure of the anterior uterine wall, and the fetus was delivered through a vertical uterine incision. The woman recovered and 6 months later has no genitourinary complaints.

Abnormalities, Multiple↗
PubMed1991

Introduction of single-copy sequences into the chromosome of Escherichia coli: application to gene and operon fusions.

We have developed a general method for the introduction of any cloned sequence into the chromosome of Escherichia coli. This method employs an Hfr strain which carries a fragment of bla (the pBR322 gene imparting ampicillin resistance) between lacI and lacZ. Plasmid-borne inserts which are flanked by sequences from bla and lacZ can be introduced at this locus by homologous recombination. The isolation of recombinants is enhanced by selection for transfer of an integrated copy of the plasmid during conjugation. Once introduced into the chromosome, the inserted sequences can be transferred to other strains by conventional methods such as P1 transduction or conjugation. This method is suitable for the transfer of any cloned sequence to the chromosome and is particularly well suited to the construction of chromosomal gene and operon fusions with lacZ.

Ampicillin Resistance↗