Biomedical subjects

C S Lin

Publications and source records attributed to C S Lin.

At least 163 records · Page 9Linked to original sources

PubMed1994

[AIDS complicated with disseminated toxoplasmosis: a pathological study of 9 autopsy cases].

Nine autopsy cases of disseminated toxoplasmosis in New York are reported. Brain were involved in 9 cases, heart in 8, lung in 4, and pancreas, GI tract, thyroid, lymph nodes and urogenital organs were also involved. There were toxoplasma encephalitis in 9 cases, myocarditis in 4, pneumonia in 3 and pancreatitis in 2. Only toxoplasma encephalitis and pneumonia produced signs and symptoms leading to diagnosis by CT scan of brain, toxoplasma antibody titer and confirmed by smears, bone marrow biopsy and autopsy based on recognition of encysted toxoplasma. The authors classified the lesions as static (latent), necrotic, infiltrative and proliferative status, with the emphasis on the diagnostic significance of identification of toxoplasma, especially its encysted form.

AIDS-Related Opportunistic Infections↗

PubMed1994

Survival patterns among younger women with breast cancer: the effects of age, race, stage, and treatment.

Several hundred studies of breast cancer survival are published each year; yet few of them include women under the age of 50, and almost none of them specifically examine prognosis among women in their 20s through 40s. The few published reports that analyze survival after breast cancer among these young patients do not provide a consistent or definitive description of their survival experience. The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program offers a unique opportunity to analyze breast cancer survival in depth among younger women. In this report, survival patterns of all black and white women diagnosed with breast cancer between 1983 and 1989, aged 20 and older, microscopically confirmed, and undergoing surgery, in the SEER program have been analyzed. There are 77,368 women included in this study, 92.8% of whom were white. Less than 1% (562 patients) of these breast cancer patients were between the ages of 20 and 29, 6.5% (5062 patients) were 30-39, and 15.2% (11,789 patients) were 40-49. Survival was calculated utilizing a mixture model to evaluate the cause-specific hazards of dying of breast cancer versus dying of other causes of death. We investigated the hazard of dying of breast cancer versus other causes of death by age at diagnosis, year of diagnosis, extent of disease and diagnosis, and treatment. Stage was stratified into three categories: 1) cases with no axillary lymph node involvement, 2) cases with axillary lymph node involvement, and 3) cases with distant metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Case report: fatal lymphoproliferative disease seven weeks after liver transplantation.

A 42-year-old man developed a lymphoproliferative disorder and died seven weeks after undergoing liver transplantation for primary biliary cirrhosis. At autopsy, diffuse large cell lymphoma was noted to involve almost every organ. Molecular analyses of DNA isolated from an enlarged periportal lymph node indicated the presence of Epstein-Barr virus sequences and several JH immunoglobulin gene rearrangements (consistent with the presence of more than one greatly expanded clone of lymphoid cells of B-cell lineage). This case underscores the possibility of the rapid emergence of lymphoproliferative disorder related to Epstein-Barr virus early after liver transplantation, masked by a concurrent episode of acute rejection.

Adult↗

PubMed1993

Alternative extracellular and cytoplasmic domains of the integrin alpha 7 subunit are differentially expressed during development.

Examination of cDNAs for the laminin-binding alpha 7 integrin subunit identified two different sequences (designated X1 and X2) coding for the variable region between the III and IV homology repeat domains near the putative ligand-binding site. Sequencing of a mouse alpha 7 genomic clone established that the X1 and X2 regions are derived by mutually exclusive alternative mRNA splicing. Reverse transcriptase-polymerase chain reaction analysis of alpha 7 mRNA indicated that the X1 and X2 isoforms were present in equal amounts in mouse skeletal myoblasts and adult heart. However, in adult skeletal muscle, the X2 variant was exclusively expressed. Amino acid sequence homologies in the III/IV segment suggest that alpha 3 and alpha 6 are also alternatively spliced at this site. We identified alternatively spliced exons in a human alpha 6 genomic clone that encode X1- and X2-like segments. Analysis of the alpha 7 cytoplasmic domain indicated that this region was also alternatively spliced and like alpha 3 and alpha 6 could exist as the A or B form. In mouse skeletal and cardiac muscle the B form of alpha 7 was strongly expressed. However, we identified alpha 7A in neonate and adult skeletal muscle but not in cardiac tissue. High levels of alpha 7A were detected in differentiating myotubes, but in proliferating myoblasts only the alpha 7B isoform was present. These results indicate that alternative splicing of alpha 7 mRNA is differentially regulated during development and generates variant integrin chains with structurally and presumably functionally unique ligand-binding and cytoplasmic domains.

Alternative Splicing↗

PubMed1993

Breast cancer among black and white women in the 1980s. Changing patterns in the United States by race, age, and extent of disease.

BACKGROUND: This national study of breast cancer incidence and mortality was conducted to determine whether patterns of change differ for black and white women, to evaluate patterns by extent of disease, and to determine whether recent patterns of breast cancer are consistent with results that one would expect due to increases in use of screening examinations by women. METHODS: The study included 104,351 cases of in situ or invasive breast cancer diagnosed between 1983 and 1989 among women from the nine geographic areas participating in the National Cancer Institute Surveillance, Epidemiology, and End Results program. Breast cancer incidence patterns were examined by extent of disease for black and white women and by age at diagnosis. RESULTS: Significant increases occurred in the incidence of all early-stage breast cancers. Concomitantly, significant decreases occurred in the incidence of the most advanced-stage breast cancers. Although both white and black women experienced significant increases in early-stage breast cancer, black women have substantially lower rates of the least extensive breast cancers. CONCLUSIONS: These results strongly suggest that a major explanation for the increase in breast cancer incidence in the 1980s may well be the increased prevalence of breast cancer screening among women in the United States. They also suggest a consistent benefit of screening across all age groups from 40 to 49 years through 70 years and older.

Adult↗

PubMed1993

Alpha 6 integrin is up-regulated in step increments accompanying neoplastic transformation and tumorigenic conversion of human fibroblasts.

Integrins are a family of transmembrane glycoproteins that serve as cell-cell and cell-substratum adhesion molecules and help regulate cellular differentiation and proliferation. In malignant cells, which exhibit abnormal differentiation and growth properties, the expression of an altered integrin repertoire could therefore be expected. From a tumorigenic human fibrosarcoma cell line we isolated a unique complementary DNA corresponding to the alpha 6 integrin subunit. Northern blot analysis using this complementary DNA as probe indicated that alpha 6 integrin mRNA was abundantly expressed in all neoplastically transformed fibroblast cell lines but not in normal diploid fibroblasts. In addition to its potential as a marker for the neoplastic transformation of human fibroblasts, the alpha 6 integrin mRNA was also found to be consistently expressed at higher levels in tumorigenic fibroblasts than in immortalized but nontumorigenic fibroblasts. This differential expression of alpha 6 integrin was reflected at the cell surface protein level using cytofluorometric analysis with specific monoclonal antibody. In contrast, the levels of cell surface expression of other integrins were unchanged (such as alpha 3 and beta 1) or down-regulated (such as alpha 5) when transformed cells were compared with normal fibroblasts. The incremental up-regulation of alpha 6 integrin was selective and paralleled the progression of normal cells to immortalized cells and finally to tumorigenic cells. This elevated alpha 6 subunit associated with the beta 1 subunit to form a heterodimer receptor for laminin. Since fibrosarcoma cell invasion of basement membrane has been shown to involve alpha 6 beta 1 integrin, then the induction or up-regulation of alpha 6 expression is an important step in tumor progression and evolution to the invasive phenotype in fibrosarcoma.

Animals↗

PubMed1993

Expression of smooth muscle and nonmuscle tropomyosins in Escherichia coli and characterization of bacterially produced tropomyosins.

The cDNA encoding the beta-tropomyosin isoform of chicken smooth muscle (CSM beta) was constructed and expressed in Escherichia coli to produce recombinant, unacetylated beta-tropomyosin (rCSM beta) and a mutant (rCSM beta-7) with a 7-residue deletion at its amino-terminus. Furthermore, the cDNA coding for human fibroblast tropomyosin isoform 3 (hTM3) was also used to produce unacetylated hTM3 (called PEThTM3). All of bacterially-made tropomyosins were high alpha-helical in structure as judged by CD analysis and resistant to heat denaturation. Both the rCSM beta and PEThTM3 exhibited saturable binding to F-actin with apparent binding constants of 1.14 x 10(6) and 2.78 x 10(6) M-1, respectively. The bacterially made, unacetylated smooth muscle tropomyosin (rCSM beta) appeared to have a comparable actin-binding affinity to that of gel-purified CSM beta homodimer (1.25 x 10(6) M-1) but significantly lower than that for native gizzard tropomyosin (CSM-TM) heterodimer (1.28 x 10(7) M-1). The amino-terminal deletion mutant rCSM beta-7 failed to bind to F-actin. Effects of gizzard caldesmon on the actin binding of these bacterially made tropomyosins were also examined. Under the binding condition containing 0.5 mM MgCl2 and 30 mM KCl, caldesmon greatly enhanced the binding of rCSM beta to F-actin. However, under the same condition, there was a slight enhancement in the actin-binding for gel-purified CSM beta or PEThTM3 (1.2-1.6-fold stimulation) and no enhancement for native gizzard tropomyosin. Neither the presence of caldesmon nor native gizzard tropomyosin induced detectable binding of the amino-terminal deletion mutant rCSM beta-7 to F-actin. These results clearly imply the importance of the amino-terminal 7 amino-acid residues of CSM beta in the actin binding and the caldesmon enhancement.

Actins↗

PubMed1993

Voltage-gated potassium channels regulate calcium-dependent pathways involved in human T lymphocyte activation.

The role that potassium channels play in human T lymphocyte activation has been investigated by using specific potassium channel probes. Charybdotoxin (ChTX), a blocker of small conductance Ca(2+)-activated potassium channels (PK,Ca) and voltage-gated potassium channels (PK,V) that are present in human T cells, inhibits the activation of these cells. ChTX blocks T cell activation induced by signals (e.g., anti-CD2, anti-CD3, ionomycin) that elicit a rise in intracellular calcium ([Ca2+]i) by preventing the elevation of [Ca2+]i in a dose-dependent manner. However, ChTX has no effect on the activation pathways (e.g., anti-CD28, interleukin 2 [IL-2]) that are independent of a rise in [Ca2+]i. In the former case, both proliferative response and lymphokine production (IL-2 and interferon gamma) are inhibited by ChTX. The inhibitory effect of ChTX can be demonstrated when added simultaneously, or up to 4 h after the addition of the stimulants. Since ChTX inhibits both PK,Ca and PK,V, we investigated which channel is responsible for these immunosuppressive effects with the use of two other peptides, noxiustoxin (NxTX) and margatoxin (MgTX), which are specific for PK,V. These studies demonstrate that, similar to ChTX, both NxTX and MgTX inhibit lymphokine production and the rise in [Ca2+]i. Taken together, these data provide evidence that blockade of PK,V affects the Ca(2+)-dependent pathways involved in T lymphocyte proliferation and lymphokine production by diminishing the rise in [Ca2+]i that occurs upon T cell activation.

Calcium↗

PubMed1993

Human plastin genes. Comparative gene structure, chromosome location, and differential expression in normal and neoplastic cells.

Plastins are a family of actin-binding proteins that are conserved throughout eukaryote evolution and expressed in most tissues of higher eukaryotes. In humans, two ubiquitous plastin isoforms (L and T) have been identified. The L isoform is expressed only in hemopoietic cell lineages, while the T isoform has been found in all other normal cells of solid tissues that have replicative potential (fibroblasts, endothelial cells, epithelial cells, melanocytes, etc.). However, L-plastin has been found in many types of malignant human cells of non-hemopoietic origin suggesting that its expression is induced accompanying tumorigenesis in solid tissues. To learn more about the nature of plastin genes and their potential role in malignancy, the L- and T- plastin genes were cloned and sequenced to characterize their structure and mechanisms of regulation of expression. Each gene was found to be approximately 90 kilobases in size and was composed of 16 exons. All exon-intron junction sequences were identified and shown to conform to the canonical junction sequences. It was evident from their similar structure and coding homology that the two plastin genes have diverged from a common ancestor gene. L- and T-plastin genes were also mapped to chromosomes 13 and X, respectively, using polymerase chain reaction amplification with isoform-specific probes. An expanded survey of normal cell types and 50 tumor cell lines, demonstrated that 68% of carcinomas and 53% of other solid tumors of nonepithelial origin exhibited L-plastin expression, whereas the normal stem cell progenitors did not. Fibrosarcomas (n = 4), ovarian carcinomas (n = 9), breast carcinomas (n = 4), and choriocarcinomas (n = 2) combined exhibited the highest frequency and levels of L-plastin expression (95% frequency). In addition, 4 tumor cell lines that were L-plastin-negative exhibited evidence of defective T-plastin expression increasing the apparent co-incidence of plastin abnormalities associated with human tumorigenesis to 71%. Evidence is presented in support of a trans-activation mechanism for activation of L-plastin synthesis accompanying tumorigenesis. The induction of L-plastin expression accompanying SV40-mediated transformation of human embryonic lung MRC-5 fibroblasts was also confirmed. Finally, we present evidence that fimbrin is a third distinct plastin isoform which is specifically expressed at high levels in the small intestine.

Amino Acid Sequence↗

PubMed1993

Characterization of the human L-plastin gene promoter in normal and neoplastic cells.

Plastins are a family of human actin-binding proteins (isoforms) which are abundantly expressed in all normal replicating mammalian cells. One isoform, L-plastin, is constitutively expressed at high levels in hemopoietic cell types while T-plastin is constitutively expressed in all non-hemopoietic cells of solid tissues that have replicative potential (fibroblasts, endothelial cells, epithelial cells, melanocytes, etc.). L-plastin is, however, constitutively synthesized in many types of malignant human cells of solid tissues suggesting that its expression is induced during tumorigenesis. The frequency of L-plastin induction in some cancers of the steroid-regulated female reproductive tract (breast, ovary, uterus, and placenta) appears to be especially high (79% in a limited survey). To learn the mechanism of L-plastin gene activation accompanying tumorigenesis, we have begun to characterize the promoter and regulatory elements of the L-plastin gene. Transcription initiation from this promoter was found to occur at multiple sites and as near as 10 base pairs from the 3'-side of the TATAAA box. The promoter and its flanking DNA were cloned and sequenced to identify potential regulatory elements that participate in the induction of the L-plastin gene in neoplastic cells. Examination of upstream sequences revealed the existence of two potential progesterone, one potential estrogen, and four potential Ets-1 responsive elements flanking the promoter. A 315-base pair fragment spanning the TATAAA box and a potential Sp1-binding site exhibited maximum promoter activity using CAT as a reporter while longer promoter fragments extending into upstream flanking sequences spanning the hormone receptor-response elements exhibited reduced promoter activity. An expression vector, pHLPPr-1-neo, was constructed using a 5.1-kilobase pair EcoRI-HindIII fragment of the L-plastin gene that contained the potential upstream regulatory elements, the TATAAA box, and part of the first exon. This promoter could direct the constitutive expression of the reporter beta-galactosidase at high frequency in transfected colonies of transformed cells that express L-plastin constitutively; by contrast, this promoter was virtually inactive in transfected colonies of normal fibroblasts and it exhibited a low frequency of constitutive activation in transfected colonies of in vitro SV40-transformed fibroblasts which did not exhibit L-plastin expression. The utility of this recombinant promoter in determining the mechanism(s) that leads to activation of the L-plastin gene in tumor cells is discussed. The potential significance of regulation of the L-plastin gene by reproductive hormones in cancers arising in hormone-responsive tissues is also discussed.

Base Sequence↗

PubMed1993

Human fibroblast tropomyosin isoforms: characterization of cDNA clones and analysis of tropomyosin isoform expression in human tissues and in normal and transformed cells.

A tropomyosin-specific oligonucleotide probe (REN29) designed to hybridize to all known human tropomyosin isoforms was used to study tropomyosin mRNA levels in normal and transformed human cells. At least four different sizes of RNAs were detected in normal human fibroblast KD cells by Northern blot analysis. The major bands of 1.1 kb RNA for hTM1 and 3.0 kb RNA for hTM4 were decreased substantially in various transformed cell lines. One of the minor RNA bands (2.0 kb for hTM2 and hTM3) appeared to be absent in a human pancreatic carcinoma cell line. The level of the other minor RNA band (2.5 kb for hTM5) was found to be unchanged or slightly decreased in transformed cells. This differential expression of tropomyosin isoforms at the RNA level was not totally in agreement with the difference in the protein amounts found in normal and transformed cells, suggesting that translational control may also play an important role in the expression of some tropomyosin isoforms. The REN29 probe was further used to screen lambda gt10 and lambda gt11 cDNA libraries, which were constructed from poly(A)+ RNAs of human fibroblast cell lines HuT-14 and WI-38, respectively. In addition to cDNA clones encoding known isoforms, we obtained three classes of new cDNA clones that encode two low M(r) isoforms (hTM5a and hTM5b), and a high M(r) isoform (hTMsm alpha). Sequence comparison revealed that hTM5a and hTM5b are alternatively spliced products derived from the same gene that encodes hTM2 and hTM3. Northern blot analysis and amino acid sequence comparison suggested that the hTMsm alpha represents a smooth muscle tropomyosin which is also expressed in human fibroblasts. The exon specific for, and common to, hTM5a and hTM5b was found to be highly expressed in small intestine. However, there was no detectable expression of this exon in stomach and skeletal muscle. The difference in tissue-specific expression suggests that different isoforms may perform distinct functions in different tissues.

Amino Acid Sequence↗

PubMed1993

Central nervous system Strongyloides stercoralis in acquired immunodeficiency syndrome: a report of two cases and review of the literature.

Hyperinfection with Strongyloides stercoralis is rare in acquired immunodeficiency syndrome (AIDS), despite endemicity in areas where infection with human immunodeficiency virus is highly prevalent. We autopsied two patients with AIDS and disseminated Strongyloides and describe their central nervous system findings. The microscopic patterns of brain infection were dissimilar in the two patients, and reflected histology in systemic viscera. In one patient, a granulomatous response accompanied filariform larvae in all locations, including granulomatous ependymitis in brain. Additionally in the brain, larvae without tissue reaction were seen. In the second patient, the absence of tissue response to larvae was body wide, and isolated parasites were found in centrum semiovale. The occurrence of these patients in a region where Strongyloides is not endemic suggests that this infection may be more prevalent in AIDS than formerly suspected.

Acquired Immunodeficiency Syndrome↗

PubMed1993

Tissue distribution and excretion of 14C-labelled cinnamic aldehyde following single and multiple oral administration in male Fischer 344 rats.

14C-labelled cinnamic aldehyde (CNMA) was given as a single oral dose, or 24 hr after multiple oral administration of non-radioactive CNMA for 7 days at 24-hr intervals, to male Fischer 344 rats at dose levels of 5, 50 or 500 mg/kg body weight. Residues of radioactive CNMA were measured. After the single dose radioactivity was distributed primarily in the gastro-intestinal tract, the kidneys and the liver of the rats. The radiolabel was excreted mainly in the urine, and at 24 hr 85.1, 84.2 and 81.2% of the administered radiolabel was recovered in the urine at the 5, 50 and 500 mg/kg dose levels, respectively. Faecal excretion of radiolabel at 24 hr for the 5, 50 and 500 mg/kg doses was 5.1, 4.0 and 3.2% of the administered dose, respectively. At all dose levels, a small amount of the dose was distributed to the fat and was easily measured in animals killed 3 days after dosing at the 50 or 500 mg/kg dose levels. Following multiple oral administration, similar tissue distribution and excretion patterns of radiolabel were found at the three dose levels. After 24 hr the administered radiolabel was distributed mainly to the fat, liver and gastro-intestinal tract. At 24 hr, recoveries of the radiolabel in the urine were 80.4, 80.6 and 81.9% of the dose for the 5, 50 and 500 mg/kg dose levels, respectively. Faecal excretion of radiolabel after multiple dosing at 24 hr accounted for 6.3, 6.9 and 4.5% of the administered radioactivity at the 5, 50 and 500 mg/kg dose levels, respectively. The major metabolic pathway of CNMA for all single and the 5 and 50 mg/kg multiple dose levels in this species of rat was found to be degradation to benzoic acid through beta-oxidation and excretion in the urine mainly as hippuric acid, with much smaller amounts of benzoic and cinnamic acids. At the multiple dose level of 500 mg/kg, benzoic acid was the major urinary metabolite, indicating that in the Fischer 344 male rat at this relatively high oral dose level the detoxification of CNMA proceeds differently and an alternative metabolic pathway is proposed.

Acrolein↗

PubMed1993

De novo expansion of a (CAG)n repeat in sporadic Huntington's disease.

Huntington's disease (HD) chromosomes contain an expanded unstable (CAG)n repeat in chromosome 4p16.3. We have examined nine families with potential de novo expression of the disease. With one exception, all of the affected individuals had 42 or more repeat units, well above the normal range. In four families, elderly unaffected relatives inherited the same chromosome as that containing the expanded repeat in the proband, but had repeat lengths of 34-38 units, spanning the gap between the normal and HD distributions. Thus, mutation to HD is usually associated with an expansion from an already large repeat.

Adult↗

PubMed1993

Validity and feasibility of nasopharyngeal end-tidal carbon dioxide tension monitorings: a novel approach in spontaneous breathing patients.

Conventional end-tidal CO2 (Pe'CO2) monitoring is difficult and impractical in nonintubated patients who are either sedated or anesthetized while spontaneous respiration is maintained. An alternative technique using nasopharyngeal end-tidal carbon dioxide tension (PNe,CO2) has been developed. The present study evaluates the feasibility and validity of PNe,CO2 as a reliable respiratory monitoring method. Sixty patients in ASA class status I or II and scheduled for elective surgery were divided into two groups. In group 1 (n = 30), conventional Pe'CO2 was used in intubated patients under general anesthesia. In group 2 (n = 30), PNe,CO2 monitoring was used in patients under regional anesthesia with spontaneous respiration maintained. A 12 FG suction catheter, connected to the sampling tube of a CO2 analyzer, was inserted via the nasal airway to within 1 cm of the nasopharyngeal orifice. Arterial blood gas (PaCO2) was sampled 25 minutes after the operation began, Pe'CO2 (group 1) and PNe,CO2 (group 2) were recorded simultaneously. In both groups, PaCO2 was highly correlated with Pe'CO2 (r = 0.6938) and PNe,CO2 (r = 0.8613). The difference between the two values, (a-e')PCO2 = 0.35 +/- 0.33kPa and (a-Ne')PCO2 = -0.1 +/- 0.51kPa, indicates that PNe,CO2 is more closely correlated to PaCO2 than conventional Pe'CO2. The reduced (a-Ne')PCO2 in group 2 may be explained by CO2 rebreathing and a reduced respiratory deadspace during anesthesia and spontaneous breathing. Interestingly, 60% of the (a-Ne')PCO2 measurements were negative values, suggesting that PNe,CO2 and a spatial V/Q mismatch is caused by sedation; higher CO2 production and CO2 rebreathing may explain the results.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1993

[Comparison of intravenous alfentanil, fentanyl and epidural lidocaine for extracorporeal shock wave lithotripsy].

Due to the development of newer generation of lithotriptor, the anesthesia for extracorporeal shock wave lithotripsy (ESWL) was variable recently. To compare opioid analgesia with epidural lidocaine for their efficacy in pain control, hemodynamic changes, side effects and patient acceptance during ESWL, sixty unpremedicated patients undergoing elective ESWL for upper urinary calculi with second generation Dornier MFL 5000 nonimmersion lithotriptor were randomly assigned equally into one of the following managements: Group E: 1% epidural lidocaine with 1:200000 epinephrine; Group A: 15 micrograms/kg alfentanil initially and 7 micrograms/kg on demand intravenously; Group F: 4 micrograms/kg fentanyl initially and 2 micrograms/kg on demand intravenously. Significant hypotension and bradycardia occurred in Gp.E as compared to baseline value (p < 0.05). Early respiratory depression was observed in both Gp. A and Gp. F, but Gp. A showed significantly shorter period (2 to 5 minutes) as compared to Gp.F (2 to 15 minutes). Under the insufflation of oxygen by nasal cannula, mean PaCO2 increased maximally to 50 mmHg, but no arterial oxygen desaturation (< 90%) was noted in Gp.A and Gp.F. The incidence of post-ESWL nausea was higher in Gp.F (p < 0.05), shivering and delayed recovery time were the main disturbing problems in Gp.E (p < 0.01). Although five-point verbal pain scale was significantly higher in Gp.A and Gp.F (at 30 to 45 minutes during ESWL) as compared to Gp.E, acceptance among patients was high throughout the course. We conclude that different anesthetic plans should be determined on different lithotriptors settings and patient's physical condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

The immunosuppressive and toxic effects of FK-506 are mechanistically related: pharmacology of a novel antagonist of FK-506 and rapamycin.

FK-506 inhibits Ca(2+)-dependent transcription of lymphokine genes in T cells, and thereby acts as a powerful immunosuppressant. However, its potential therapeutic applications may be seriously limited by several side effects, including nephrotoxicity and neurotoxicity. At present, it is unclear whether these immunosuppressive and toxic effects result from interference with related biochemical processes. FK-506 is known to interact with FK-binding protein-12 (FKBP-12), an abundant cytosolic protein with cis-trans peptidyl-prolyl isomerase activity (PPIase) activity. Because rapamycin (RAP) similarly binds to FKBP-12, although it acts in a manner different from FK-506, by inhibiting T cell responses to lymphokines, such an interaction with FKBP-12 is not sufficient to mediate immunosuppression. Recently, it was found that the complex of FKBP-12 with FK-506, but not with RAP, inhibits the phosphatase activity of calcineurin. Here, we used L-685,818, the C18-hydroxy, C21-ethyl derivative of FK-506, to explore further the role of FKBP-12 in the immunosuppressive and toxic actions of FK-506. Although L-685,818 bound with high affinity to FKBP-12 and inhibited its PPIase activity, it did not suppress T cell activation, and, when complexed with FKBP-12, did not affect calcineurin phosphatase activity. However, L-685,818 was a potent antagonist of the immunosuppressive activity of both FK-506 and RAP. Moreover, L-685,818 did not induce any toxicity in dogs and rats or in a mouse model of acute FK-506 nephrotoxicity, but it blocked the effect of FK-506 in this model. Therefore, FK-506 toxicity involves the disruption of biochemical mechanisms related to those implicated in T cell activation. Like immunosuppression, this toxicity is not due to the inhibition of the PPIase activity of FKBP-12, but may be linked to the inhibition of the phosphatase activity of calcineurin by the drug FKBP-12 complex.

Amino Acid Isomerases↗

PubMed1992

Production and immobilization of D-aminoacylase of Alcaligenes faecalis DA1 for optical resolution of N-acyl-DL-amino acids.

The production of D-aminoacylase by Alcaligenes faecalis DA1 was induced 5- to 50-fold by N-acetyl-D-amino acids. This strain produced about 443 units of D-aminoacylase and 52 units of L-aminoacylase per gram of cells (wet weight) when cultivated in a medium containing 1% N-acetyl-DL-leucine as the carbon source. The D-aminoacylase was partially purified by Fractogel DEAE 650 column chromatography and then immobilized on another Fractogel DEAE 650 column. The catalytic activity of the immobilized D-aminoacylase was 2,650 units per milliliter of gel. The Km values for the free and the immobilized enzymes were found to be 1.00 and 0.22 mM, respectively, using N-acetyl-D-methionine as a substrate. The optimal reaction pH and temperature for both soluble and immobilized enzyme were around 8.0 and 45 degrees C, respectively. The free enzyme was stable in the pH range from 5.0 to 11.0, whereas the immobilized enzyme tended to detach from the gel at pH values higher than 9.0. Both forms of enzyme were stable up to 40 degrees C. When used for the optical resolution of N-acetyl-DL-methionine, the immobilized enzyme maintained 90% initial activity after 17 days of continuous operation at 45 degrees C. The process of purification and immobilization of D-aminoacylase described in this report is very effective and easy to scale up.

Alcaligenes↗