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Biomedical subjects

A Yu

Publications and source records attributed to A Yu.

At least 91 records · Page 5Linked to original sources

Hardness anisotropy of acetaminophen crystals.

The anisotropy of acetaminophen hardness was demonstrated using both Vickers and Knoop indentation hardness measurements. Based on a model of Knoop hardness anisotropy proposed by Brookes et al. (1), it was concluded that plastic flow in acetaminophen crystals occurs primarily as a result of slip in the (010)<001> system. This conclusion was corroborated with the results of the Vickers indentation tests. The apparent brittleness of acetaminophen was rationalized because only one slip system appeared to be operative. Under these conditions generalized plastic flow cannot occur, since this requires the operation of at least five independent slip systems (2). The high stress concentrations that result from flow lead to fracture. Therefore acetaminophen is more precisely classified as being semiductile. When a material deforms plastically as a result of slip in only one slip system, considerable crystal realignment can occur during compaction. This in turn can facilitate capping during decompression and ejection, since the cleavage plane, (010), would become aligned with the direction of highest tensile stress.

Acetaminophen↗

Phase II trial of amonafide in patients with advanced metastatic or recurrent endometrial adenocarcinoma. A Southwest Oncology Group study.

Amonafide, a benzisoquinoline-1,3-dione was administered to 38 patients with recurrent or metastatic, bidimensionally measurable endometrial cancer. There were 34 patients with no prior cytotoxic chemotherapy, performance status of 0-2, and normal bone marrow, renal, and hepatic function were eligible for response and toxicity evaluation. Amonafide, 300 mg/m2, was administered intravenously over 1 hour daily for 5 consecutive days. Courses were repeated every 21 days. The major grade 3 or 4 toxicities were hematologic with granulocytopenia in 18 patients (53%), thrombocytopenia in 6 patients (18%), and anemia in 8 patients (24%). Infectious complications occurred in 3 patients (9%). Other side effects included cardiac dysrhythmias, hypotension, pain and phlebitis at the site of injection, nausea, vomiting, and flu-like symptoms. The overall objective response rate was 6% (95% confidence interval of 1-20%); 2 patients had a complete response (6%), 9 patients had stable disease (26%) and 21 patients had progressive disease (62%). Two patients had insufficient follow-up for response determination and are assumed to be nonresponders. The median survival of the eligible patients was 8 months. With the toxicity observed and the low response rate, amonafide at this dose and schedule has no efficacy in the treatment of endometrial cancer.

Adenine↗

Regulation of int gene expression in bacteriophage P2.

The int gene of bacteriophage P2 is the only viral gene necessary for the integration of P2 into the Escherichia coli host chromosome. This gene is situated between the phage attachment site, attP, and the repressor C gene, and is cotranscribed with C from the Pc promoter, towards attP. The Pc promoter is negatively controlled by the cox gene, which is the first gene of the early operon. In vitro recombination assays have indicated that in P2 an overproduction of Int is deleterious to the integrative process. We report here that the level of int expression is affected by several different mechanisms after transcriptional initiation. First, a partial transcription termination signal located between the int and C genes reduces the the transcriptional readthrough by about 30%. Second, the ribosome binding site and AUG codon of the int gene are located in a putative stem-loop structure, which may inhibit the initiation of translation. The nip1 mutation (a G to A substitution at the 22nd coding nucleotide of int which results in an increased efficiency of excision) is shown to relieve this inhibition, possible through the formation of an alternative mRNA secondary structure. However, the third and probably most important control of int expression in P2 seems to be that of posttranscriptional autoregulation. The binding site of the Int protein on int gene mRNA is shown to extend into the ribosome binding site of int, supporting our earlier proposed model of competitive binding between Int and ribosomes.

Amino Acid Sequence↗

[Investigations on the present status of infections with Chlamydia trachomatis (Ct), Mycoplasma hominis (Mh) and Ureaplasma urealyticum (Uu) in patients with venereal diseases, sexual abusers and healthy people in Da Lian].

From January to June 1992, we conducted the detection of serum antibodies against Ct, Mh and Uu in patients with venereal diseases, sexual abusers and healthy people. The results showed that the positive rates of antibodies against Ct, Mh and Uu in patients were the highest, while in healthy people those of antibodies against Ct and Uu were the lowest. The positive rates between the antibody against Uu and that against Mh have no obvious difference between male and female. All samples have dual infection of Ct and Mh.

Adolescent↗

The Cox protein is a modulator of directionality in bacteriophage P2 site-specific recombination.

The P2 Cox protein is known to repress the Pc promoter, which controls the expression of the P2 immunity repressor C. It has also been shown that Cox can activate the late promoter PLL of the unrelated phage P4. By this process, a P2 phage infecting a P4 lysogen is capable of inducing replication of the P4 genome, an example of viral transactivation. In this report, we present evidence that Cox is also directly involved in both prophage excision and phage integration. While purified Cox, in addition to P2 Int and Escherichia coli integration host factor, was required for attR x attL (excisive) recombination in vitro, it was inhibitory to attP x attB (integrative) recombination. The same amounts of Int and integration host factor which mediated optimal excisive recombination in vitro also mediated optimal integrative recombination. We quantified and compared the relative efficiencies of attB, attR, and attL in recombination with attP and discuss the functional implications of the results. DNase I protection experiments revealed an extended 70-bp Cox-protected region on the right arm of attP, centered at about +60 bp from the center of the core sequence. Gel shift assays suggest that there are two Cox binding sites within this region. Together, these data support the theory that in vivo, P2 can exert control over the direction of recombination by either expressing Int alone or Int and Cox together.

Bacterial Proteins↗

Characterization of the binding sites of two proteins involved in the bacteriophage P2 site-specific recombination system.

Integration of the bacteriophage P2 genome into the Escherichia coli host chromosome occurs by site-specific recombination between the phage attP and E. coli attB sites. The phage-encoded 38-kDa protein, integrase, is known to be necessary for both phage integration as well as excision. In order to begin the molecular characterization of this recombination event, we have cloned the int gene and overproduced and partially purified the Int protein and an N-terminal truncated form of Int. Both the wild-type Int protein and the integration host factor (IHF) of E. coli were required to mediate integrative recombination in vitro between a supercoiled attP plasmid and a linear attB substrate. Footprint experiments revealed one Int-protected region on both of the attP arms, each containing direct repeats of the consensus sequence TGTGGACA. The common core sequences at attP and attB were also protected by Int from nuclease digestion, and these contained a different consensus sequence, AA T/A T/A C/A T/G CCC, arranged as inverted repeats at each core. A single IHF-protected site was located on the P (left) arm, placed between the core- and P arm-binding site for Int. Cooperative binding by Int and IHF to the attP region was demonstrated with band-shift assays and footprinting studies. Our data support the existence of two DNA-binding domains on Int, having unrelated sequence specificities. We propose that P2 Int, IHF, attP, and attB assemble in a higher-order complex, or intasome, prior to site-specific integrative recombination analogous to that formed during lambda integration.

Bacterial Proteins↗

Amphicrine carcinoma of the uterine cervix.

A case of amphicrine carcinoma of the uterine cervix is described in a 27-year-old woman whose initial cervical biopsy specimen showed small cell undifferentiated neuroendocrine carcinoma. Despite an initial complete clinical response to VP-16 and carboplatin, residual tumor was noted in the cervical cone biopsy specimen and she was treated with external-beam irradiation and cesium implants. The neoplasm subsequently metastasized and required additional VP-16 and carboplatin for control. The pathologic features and biologic behavior of this unusual type of neuroendocrine neoplasm are described in this case report.

Adult↗

Anti-promoting effect of nordihydroguaiaretic acid on N-butyl-N-(4-hydroxybutyl)nitrosamine and sodium saccharin-induced rat urinary bladder carcinogenesis.

The effects of oral administration of nordihydroguaiaretic acid (NDGA), an antioxidant and inhibitor of arachidonic acid metabolism, on rat bladder carcinogenesis were examined. Six-week-old male Fischer 344 rats were given drinking water containing 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine for 4 weeks. Following this 4-week period, diet containing 5% sodium saccharin (SS) with or without 0.1% NDGA supplement was given to the rats for 36 weeks. The incidences of papillary or nodular (PN) hyperplasia and of papilloma in the group treated with SS plus NDGA were significantly lower than those in the group treated with SS alone. The number of PN hyperplasic foci per 10 cm of basement membrane in rats treated with SS plus NDGA was also lower than that in the group treated with SS alone. These results suggest that NDGA has an anti-tumor-promoting effect on rat bladder carcinogenesis.

Animals↗

Xerostomia in diabetes mellitus.

OBJECTIVE: To determine the prevalence of xerostomia in a group of ambulatory diabetic patients and to compare the following in patients with and without xerostomia: 1) flow rates of saliva and lacrimal fluid, 2) the presence of other symptoms suggestive of oral and extraoral dryness, 3) indexes of glycemic control, and 4) noninvasive measures of cardiovagal autonomic nervous system function. RESEARCH DESIGN AND METHODS: Forty adult diabetic patients and an equal number of age- and sex-matched healthy nondiabetic control subjects were studied. Subjects who consumed xerogenic drugs or had other significant diseases were excluded from the study. A questionnaire was administered to all patients, and the following tests were performed: resting and stimulated flow rates on whole saliva; Schirmer's test (lacrimal fluid), serum glucose and HbA1, expiration-inspiration ratio, 30:15 ratio, Valsalva ratio, and the systolic blood pressure response to standing. RESULTS: Forty-three percent of diabetic patients complained of xerostomia, of which 82% were women. The oral dryness was not related to age or the type and duration of diabetes. Symptoms of water loss and oropharyngeal, ocular, and vaginal dryness were much more common in the xerostomic than the nonxerostomic diabetic patients. The salivary flow rates of the diabetic subjects was consistently lower than those of healthy, nondiabetic control subjects. The mean, resting, and whole-saliva flow rate was abnormally low in the diabetic patients who complained of xerostomia; no significant differences were observed for the stimulated salivary and the lacrimal flow rates. Significant inverse relationships were shown between salivary flow and the level of HbA1; none were shown between flow and autonomic function. CONCLUSIONS: Dry mouth is a common complaint among ambulatory diabetic patients. It is strongly associated with objective measurements of poor salivary flow and with other oral and extraoral symptoms of desiccation. The oral dryness is not associated with cardiovagal autonomic system dysfunction but may be due to disturbances in glycemic control.

Adult↗

[A case of advanced seminoma treated effectively with single agent carboplatin therapy].

Cisplatin has played a major role in the treatment of germ cell tumors. However, it causes renal damage, severe nausea and vomiting. It is also neurotoxic and ototoxic. Carboplatin is an analog of cisplatin which, does not cause renal damage at therapeutic doses. It is not neurotoxic or ototoxic and it produces less gastrointestinal toxicity than cisplatin. We used carboplatin alone as an initial chemotherapy in a 36-year-old man with stage IIB seminoma. Following left radical orchiectomy the patient received 4 courses of carboplatin chemotherapy. After the first course of chemotherapy, tumor markers (LDH, beta-HCG) returned to the normal range. After 4 courses, the size of the retroperitoneal metastases was significantly reduced. The toxicity of 4 courses of carboplatin chemotherapy was generally milder than that of cisplatin-based combination chemotherapies such as PVB or VAB-6. There were no episodes of septicemia, thrombocytopenic bleeding or renal deterioration. The patient did not suffer from alopecia, neuropathy, symptomatic hearing loss, severe nausea or vomiting. Nine months after the completion of carboplatin chemotherapy, the patient remains well and free from disease progression. This case strongly suggests that single agent carboplatin therapy could be an effective and less-toxic treatment for advanced seminoma.

Adult↗

Treatment of childhood angiomatous diseases with recombinant interferon alfa-2a.

A heterogeneous group of five patients with progressive, invasive angiomatous diseases including pulmonary hemangiomatosis, angiosarcoma, or massive hemangioma with associated consumptive coagulopathy were treated with interferon alfa-2a for periods of 17 to 33 months. One patient with a large thoracic hemangioma, cardiorespiratory failure, and consumptive coagulopathy died after less than 2 months of treatment. The remaining four patients have shown beneficial responses, including (1) regression of abnormal vessels on pulmonary angiogram and improved exercise tolerance in pulmonary hemangiomatosis (two patients), (2) decreased corticosteroid and/or platelet transfusion requirements in consumptive coagulopathy (two patients), and (3) decreased size and number of tumor nodules in the one patient with angiosarcoma arising in preexisting angiomatous lesions. Responses occurred during periods of 2 to 20 months of treatment. There was no measurable progression of angiomatous lesions in any patient receiving interferon at the therapeutic dose, except possibly in the one who died. Each of the four surviving patients had improved linear growth and weight gain during interferon treatment.

Adolescent↗

Purification and characterization of a cytosolic phosphoinositide-phospholipase C (gamma 2-type) from human platelets.

A human platelet cytosolic phosphoinositide-specific phospholipase C, one of four PLC activity peaks separated by column chromatographies, designated as cPLC-I, was purified to homogeneity. The cPLC-I exhibited an apparent Mr of 145 kDa by SDS-polyacrylamide gel electrophoresis and was immunologically identified to be PLC-gamma 2. It hydrolyzed PI and PIP2 at optimum pH of 5.5-6.0. Deoxycholate and cholate inhibited the enzyme activity to hydrolyze two substrates. Calcium was required to obtain the maximal activity for PI- and PIP2-hydrolysis at concentration of 10(-3) M and 10(-5) M, respectively. Hg2+ (1 microM) inhibited strongly the enzyme activity.

Blood Platelets↗

Establishment of continuous cultures of T-cell acute lymphoblastic leukemia cells at diagnosis.

We have devised methods facilitating the establishment of continuous cultures of T-cell blasts from patients with acute lymphoblastic leukemia of T-cell type at diagnosis. The cultured cells closely resemble those of the patients at the time of diagnosis with respect to surface markers, karyotype, and T-cell receptor gene rearrangements. Cultured T-cell acute lymphoblastic leukemia (diagnosis) cells (a) are lymphocytes with a convoluted nucleus; (b) have doubling times of 24-48 h; (c) are dependent for growth on interleukin 2; (d) are reverse transcriptase negative; (e) do not form colonies in methyl cellulose; and (f) are clonal with respect to T-cell receptor beta chain rearrangements. Three T-cell acute lymphoblastic leukemia cultures had a normal diploid karyotype, and one had a 6q- deletion which was also present at the time of diagnosis.

Adolescent↗

Transcobalamin II deficiency presenting with methylmalonic aciduria and homocystinuria and abnormal absorption of cobalamin.

An infant with deficiency of transcobalamin II (TCII) presented with virtually complete failure to thrive and life-threatening pancytopenia. Methylmalonic acid and homocystine were found in the urine. The concentration of B12 in the serum was 26 pg/ml. Fibroblasts derived from the patient failed to take up labeled cobalamin in the absence of a source of TCII. Uptake was normal in the presence of TCII. Treatment with parenteral cobalamin reversed the clinical and hematological manifestations of the disease but she developed glossitis when the interval between injections was lengthened. Intestinal absorption of 57Co-cobalamin was less than 1% and remained abnormal when highly purified human intrinsic factor was given along with the labeled B12. Absorption improved when the labeled B12 was given together with rabbit TCII. The data suggest that TCII as well as intrinsic factor is required for transport of cobalamin from the intestine to the blood.

Failure to Thrive↗

Epidural anesthesia as an adjunct to retroperitoneal aortic surgery.

Recent developments in vascular surgery suggest that the retroperitoneal approach to the aorta and the use of epidural anesthesia for lower limb revascularization are associated with decreased morbidity and shorter hospital stays. By combining these principles, we sought to determine if retroperitoneal aortic surgery could be performed under epidural anesthesia and if this might be advantageous. Over a 16-month period, 57 patients underwent aortic surgery via the retroperitoneal (n = 33) or transperitoneal (n = 24) approach. In the former, epidural anesthesia was employed in 10 patients, general anesthesia in 3, and combined epidural anesthesia and general anesthesia in the remaining 20. In the transperitoneal group, general anesthesia was employed in 21 patients and combined epidural anesthesia and general anesthesia in 3. Both groups were similar in age and gender, but risk factors were predominant in the retroperitoneal group. With the exception of one death due to aspiration, there were no significant differences between the transperitoneal and retroperitoneal groups with respect to overall morbidity, pulmonary complications, and length of stay in the intensive care unit and hospital. Despite these findings, we favor the combination of epidural and general anesthesia for retroperitoneal aortic surgery. Morbidity was significantly decreased (p less than 0.05) in low-risk retroperitoneal patients when combined epidural anesthesia and general anesthesia were employed.

Adult↗