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Biomedical subjects

W Miller

Publications and source records attributed to W Miller.

At least 181 records · Page 10Linked to original sources
PubMed1990

Diminished A-LAK cytotoxicity and proliferation accompany disease progression in chronic myelogenous leukemia.

We have compared the proliferative and cytotoxic capacities of a highly purified population of recombinant interleukin-2 (rIL-2)-activated peripheral blood mononuclear cells (PBMNC), termed adherent lymphokine-activated killer cells (A-LAK), in 15 chronic phase (CP) and 10 advanced disease (AD) Ph-positive chronic myelogenous leukemia (CML) patients. The selective enrichment of CML A-LAK cells depended on their propensity to adhere to plastic and to proliferate when cultured in the presence of rIL-2 for 14 days. In both CP and AD patients, 14-day culture resulted in growth of a uniform population of large granular lymphocytes. While less than 10% of the A-LAK cells were CD56-/CD3+ (mature T lymphocytes), 82% +/- 12% of A-LAK cells from early CP patients (diagnosed less than 1 year from study), 84% +/- 3% of A-LAK cells from late CP patients (studied greater than 1 year after diagnosis), and 87% +/- 3% of A-LAK cells from AD patients were CD56+/CD3- (activated natural killer [NK] cells). No bcr gene rearrangement could be found in A-LAK cells from 13 CP and six AD CML patients studied. A-LAK cells from seven early CP CML patients displayed similar cytotoxicity against K562 (80% +/- 7% lysis at effector:target ratio of 20:1) and against Raji (80% +/- 12% lysis) compared with A-LAK from 17 normal individuals (72% +/- 3% K562 lysis, P = .21; 74% +/- 5% Raji lysis, P = .39). However, the cytotoxicity of A-LAK cells from eight late CP patients (59% +/- 5% K562 lysis, P = .02; 52% +/- 8% Raji lysis, P = .02) and that of 10 AD patients studied at any point after diagnosis (31% +/- 3% K562 lysis, P less than .001; 25% +/- 6% Raji lysis, P less than .001) was significantly lower than that of seven early CP CML patients and 17 normals. The proliferative potential of A-LAK cells from seven early CP CML patients (291 +/- 191-fold) was significantly greater than that of A-LAK cells from 17 normal individuals (23 +/- 3-fold, P = .03), eight late CP patients (46 +/- 17-fold, P = .02), and 10 AD patients (5.4 +/- 1.9-fold, P = .01). In contrast to CML A-LAK, K562 cytotoxicity of unstimulated mature peripheral blood NK cells was significantly lower in early CP CML patients than in normals and remained low at all stages of disease.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigens, CD↗
PubMed1990

Treatment of moderate/severe acute graft-versus-host disease after allogeneic bone marrow transplantation: an analysis of clinical risk features and outcome.

We have analyzed the long term outcome of 197 patients who were treated for grade II to IV acute graft-versus-host disease (GVHD) following histocompatible allogeneic bone marrow transplantation (BMT). Of 469 recipients of sibling donor allografts performed at our center between January, 1979 and October, 1987, 197 patients (42%) developed greater than or equal to grade II acute GVHD at a median of 38 days (range 9 to 98 days) post-BMT. After treatment with corticosteroids (n = 160) or other immunosuppressive therapies (n = 37), 72 patients (41% +/- 8%; 95% confidence interval [CI]) achieved complete and continuing resolution of acute GVHD after a median of 21 days of therapy. Sixty-one patients required additional immunosuppressive therapy with high dose methylprednisolone, antithymocyte globulin (ATG)/steroids, or other therapies because of refractory or progressive symptoms of acute GVHD. Seven of these 61 patients eventually obtained complete and continuing remission after 13 to 57 days (median 50) of secondary treatment. The overall rate of chronic GVHD was 70% +/- 16%; 95% CI following grade II to IV acute GVHD. Twenty-five of the 197 patients never developed chronic GVHD, resulting in a Kaplan-Meier projection of 30% +/- 8% (95% CI) cure of moderate/severe acute GVHD. Analysis of clinical features associated with complete response (CR) to acute GVHD therapy identified more favorable responses to therapy in patients without either liver or skin involvement, patients with acute lymphoblastic leukemia, and donor/recipient pairs other than male patients with female donors. Older recipient age was not associated with more resistance to GVHD treatment. CR to GVHD treatment was associated with significantly better 5-year survival: 51% +/- 14% versus 32% +/- 11% for patients with therapy resistant acute GVHD (P = .004). GVHD was a major contributing cause of death in 49 of the 90 patients who died and was often complicated by infection or interstitial pneumonitis. Control of acute GVHD through immunosuppressive therapy did not affect the risk of leukemic relapse after transplantation.

Adolescent↗
PubMed1990

Alignment of Escherichia coli K12 DNA sequences to a genomic restriction map.

We use the extensive published information describing the genome of Escherichia coli and new restriction map alignment software to align DNA sequence, genetic, and physical maps. Restriction map alignment software is used which considers restriction maps as strings analogous to DNA or protein sequences except that two values, enzyme name and DNA base address, are associated with each position on the string. The resulting alignments reveal a nearly linear relationship between the physical and genetic maps of the E. coli chromosome. Physical map comparisons with the 1976, 1980, and 1983 genetic maps demonstrate a better fit with the more recent maps. The results of these alignments are genomic kilobase coordinates, orientation and rank of the alignment that best fits the genetic data. A statistical measure based on extreme value distribution is applied to the alignments. Additional computer analyses allow us to estimate the accuracy of the published E. coli genomic restriction map, simulate rearrangements of the bacterial chromosome, and search for repetitive DNA. The procedures we used are general enough to be applicable to other genome mapping projects.

Amino Acid Sequence↗
PubMed1990

Spirituality: the silent dimension in addiction research. The 1990 leonard ball oration.

Researchers currently recognize and incorporate psychological, biomedical, and social determinants in the study of addictive behaviors. Yet spiritual aspects of addiction and recovery remain virtually unstudied, despite the fact that spirituality is given central importance in Alcoholics Anonymous and in the lives of many individuals. Traditional spiritual concepts have been relabelled to remove their transcendent dimension, and addiction researchers have acted as though spirituality plays no role in the lives of those they study. Consequently an entire class of potentially important variables is being overlooked. A majority of variance in addictive behaviors and treatment outcomes remains unexplained, a portion of which might be accounted for through the study of spiritual dependent, moderator, and independent variables. Behavioural scientists have begun to acknowledge the role of complex spiritual, moral, and decisional processes in the addictive behaviours. Though uncomfortable in some ways for both believers and unbelievers, the scientific study of spiritual processes may improve our understanding of the addictive behaviours, and our ability to prevent and treat these enduring problems.

Journal Article↗
PubMed1990

An algorithm for searching restriction maps.

This paper presents an algorithm that searches a DNA restriction enzyme map for regions that approximately match a shorter 'probe' map. Both the map and the probe consist of a sequence of address-enzyme pairs denoting restriction sites, and the algorithm penalizes a potential match for undetected or missing sites and for discrepancies in the distance between adjacent sites. The algorithm was designed specifically for comparing relatively short DNA sequences with a long restriction map, a problem that will become increasing common as large physical maps are generated. The algorithm has been used to extract information from a restriction map of the entire Escherichia coli genome.

Algorithms↗
PubMed1990

A space-efficient algorithm for local similarities.

Existing dynamic-programming algorithms for identifying similar regions of two sequences require time and space proportional to the product of the sequence lengths. Often this space requirement is more limiting than the time requirement. We describe a dynamic-programming local-similarity algorithm that needs only space proportional to the sum of the sequence lengths. The method can also find repeats within a single long sequence. To illustrate the algorithm's potential, we discuss comparison of a 73,360 nucleotide sequence containing the human beta-like globin gene cluster and a corresponding 44,594 nucleotide sequence for rabbit, a problem well beyond the capabilities of other dynamic-programming software.

Algorithms↗
PubMed1990

Maternal serum screening for aneuploid pregnancy by alpha-fetoprotein, hCG, and unconjugated estriol.

A number of serum screening protocols are either currently in use or proposed to identify pregnant women under 35 years of age who are at increased risk for a Down syndrome fetus. It has been suggested that these same screening methods be applied to gravidas over 35 years of age to identify those women who should be offered amniocentesis. To evaluate the efficacy of screening for detection of aneuploid pregnancy in this age group, the serum samples of 34 women who underwent amniocentesis and who had confirmed fetal aneuploidy were assayed for alpha-fetoprotein (AFP), hCG, and unconjugated estriol (E3). These concentrations were compared with those of 85 women with known euploid pregnancy who underwent amniocentesis for advanced maternal age. The mean multiple of the median (MoM) for each of the three markers was significantly different from control values in cases of trisomy 21 (AFP median MoM = 0.82; unconjugated E3 median MoM = 0.77; and hCG median MoM = 1.89). These differences were not found when other aneuploidies were considered. Likelihood ratios were calculated for cases and controls and examined for their ability to predict the need for amniocentesis, based on currently recommended risk levels. There was a significant difference between the mean likelihood ratio for cases of trisomy 21 compared with that of controls (mean likelihood ratio = 13.48); there was no significant difference for other aneuploidies (mean likelihood ratio = 1.08). Of the 16 cases of trisomy 21 analyzed, four would not have been diagnosed antenatally if recommendation against amniocentesis had been made based on each woman's individual age-specific risk as modified by her likelihood ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗
PubMed1990

[Effect of enteral and parenteral nutrition on glucose tolerance in the early postoperative phase].

In a randomized clinical trial in 24 patients with colorectal resections the different behaviour of glucose tolerance (GT) in the early post-operative period was investigated. Especially, we were concerned with the way nutritional substrate were applicated. Therefore 2 groups were randomly formed for a six day period of enteral versus parenteral nutrition. To check the GT enteral tolerance-tests were done preoperatively, and on day 1, 3 and 6 postoperatively. Our results show a significant improvement of GT in the enteral group on 3, and 6, postoperative days, as well as a significantly higher insulin secretion on 3, postoperative day. C-Peptide displays similar high concentrations as a sign of elevated insulin secretion. These results prove, that enteral glucose application is superior to the parenteral way in early postoperative nutrition.

C-Peptide↗
PubMed1989

Adherent lymphokine-activated killer cells in chronic myelogenous leukemia: a benign cell population with potent cytotoxic activity.

We generated a homogeneous population of cells with cytotoxic activity termed "adherent lymphokine-activated killer" (ALAK) cells from the peripheral blood of nine patients in the chronic phase of Ph1 positive chronic myelogenous leukemia (CML). The selective enrichment of CML ALAK cells depended on their propensity to adhere to plastic and proliferate when cultured in the presence of recombinant interleukin-2 (rIL-2) for 14 days. Culture of peripheral blood mononuclear cells under these conditions resulted in growth of a uniform population of cells with morphologic characteristics of large granular lymphocytes. The NKH1+/CD3- phenotype associated with IL-2-stimulated natural killer (NK) cells was present on 79% +/- 9% of cells. Absence of colony formation in conditions promoting the growth of CFU-GEMM indicated that the CML ALAK population was not contaminated with viable hematopoietic progenitors. Cytogenetic analysis of the CML ALAK population revealed 119/120 Ph1 negative metaphases and l/120 Ph1 positive metaphase in six patients. Southern blot analysis of CML ALAK failed to demonstrate a bcr gene rearrangement in seven patients known to have a bcr gene rearrangement in myeloid cells. Comparison of ALAK populations derived from peripheral blood of CML patients and normals revealed similar cytotoxicity against the NK-sensitive K562 cell line (104 +/- 36 LU v 88 +/- 19 LU; P = NS) and the NK-resistant Raji cell line (93 +/- 26 LU v 98 +/- 28 LU; P = NS). The proliferative capacity of CML ALAK cells (101 +/- 33 fold expansion) exceeds the growth potential of the normal ALAK cells (22.3 +/- 3 fold expansion; P = .02). Direct comparison of equal numbers of CML ALAK cells and a CML LAK cell population produced by incubation of peripheral blood mononuclear cells in rIL-2 for 14 days without adherence revealed that the CML LAK population had significantly lower lytic activity against K562 and Raji cell lines. We are able to expand CML peripheral blood mononuclear cells to provide a population of ALAK cells with potent cytotoxic activity. The CML ALAK population is relatively homogeneous, not contaminated with viable stem cells, not derived from a malignant lineage, and more cytotoxic than equal numbers of CML LAK cells. Further studies are underway to determine if this ALAK population may be effective in autologous killing of chronic myelogenous leukemia stem cells.

Azure Stains↗
PubMed1989

Approximate matching of regular expressions.

Given a sequence A and regular expression R, the approximate regular expression matching problem is to find a sequence matching R whose optimal alignment with A is the highest scoring of all such sequences. This paper develops an algorithm to solve the problem in time O(MN), where M and N are the lengths of A and R. Thus, the time requirement is asymptotically no worse than for the simpler problem of aligning two fixed sequences. Our method is superior to an earlier algorithm by Wagner and Seiferas in several ways. First, it treats real-valued costs, in addition to integer costs, with no loss of asymptotic efficiency. Second, it requires only O(N) space to deliver just the score of the best alignment. Finally, its structure permits implementation techniques that make it extremely fast in practice. We extend the method to accommodate gap penalties, as required for typical applications in molecular biology, and further refine it to search for sub-strings of A that strongly align with a sequence in R, as required for typical data base searches. We also show how to deliver an optimal alignment between A and R in only O(N + log M) space using O(MN log M) time. Finally, an O(MN(M + N) + N2log N) time algorithm is presented for alignment scoring schemes where the cost of a gap is an arbitrary increasing function of its length.

Algorithms↗
PubMed1989

Design and performance of a high speed driver circuit for PIN diode switches used in microwave hyperthermia.

In many cancer treatment facilities where hyperthermia treatments are performed, there is a need to split a single channel microwave source into multiple, individually controllable channels. In the application reported here, microwave power is alternately switched between active and passive elements for each channel. The active element is either a microwave antenna inside a catheter in tumour tissue or a planar spiral applicator placed superficially, the total power to each channel being pulse width modulated from 1 to 99% of a 1 s duty cycle. The system is computer controlled and is capable of dividing and controlling power to 12 channels. PIN diode switch assemblies control the flow of power in each channel but they must be switched within a few microseconds to avoid failure at the high power levels used in the clinic. A high speed circuit was fabricated and tested to drive each PIN diode switch; the PIN diode switches are turned on in 1.5 microseconds and off in 3.0 microseconds, which meets the specifications for hot switching. The increase in speed over the former driver system is a factor of 5.1 for the on cycle and 1.5 x 10(5) for the off cycle and the maximum power tested in each channel was 80 W for 1 h at random duty cycles between 1 and 99%. The circuit was also tested with 40 W of power at duty cycles of 1, 50 and 99% for 1 h each; no failures or performance decrements were observed. The 12 channel circuit driver has been used for six months of clinical treatments without failure.

Equipment Design↗
PubMed1989

Polycystic ovaries treated by laparoscopic laser vaporization.

Eighty-five anovulatory women with polycystic ovaries were treated laparoscopically by argon, carbon dioxide (CO2) or potassium-titanyl-phosphate (KTP) laser vaporization. Ovulation occurred spontaneously postoperatively in 71%. Twenty of 38 (53%) women resistant to standard clomiphene citrate (CC) therapy ovulated spontaneously after laparoscopic laser vaporization of the ovaries. Seventeen of the remaining 18 patients responded to CC postoperatively. Of 47 patients ovulating preoperatively with CC, 40 (85%) ovulated spontaneously postoperatively. Postoperatively, 56% conceived within six months of laparoscopy. This included 58% of postoperative spontaneous ovulators and 52% of postoperative CC stimulated patients. The results suggest that selected patients with polycystic ovaries can be induced to ovulate and subsequently conceive by laparoscopically partially vaporizing their ovaries with laser energy.

Female↗
PubMed1989

Significance of mucosal vs salivary gland changes in lip biopsies in the diagnosis of chronic graft-vs-host disease.

Lip biopsy is frequently utilized to diagnose and stage chronic graft-vs-host disease (cGVHD). However, the significance of mucosal (MU) vs salivary gland (SG) involvement as well as the minimal histologic changes necessary for diagnosis remain unclear. We evaluated 68 lip and oral mucosa biopsy specimens using published diagnostic criteria. Thirty-four specimens contained both MU and SG tissue. Both MU and SG were definitely involved in 13 patients while apparent false-negatives for MU of 20% (2/10) and SG of 11% (1/9) were observed. No clinical differences were noted among the patients with both MU-alone-, or SG-alone-positive biopsy specimens. Patients with no evidence of cGVHD in either MU or SG showed significantly less other organ involvement than patients with positive evidence. Patients with minimal MU changes (rare dyskeratotic cells) were clinically indistinguishable from negative patients in terms of other organ involvement. However, 50% of the biopsy specimens with minimal MU involvement in which SG were present had definite GVHD in the SG. These data indicate that lip biopsy specimens must include both MU and SG tissue to rule out oral GVHD. Minimal MU changes are insufficient to diagnose oral cGVHD, although they do warrant close follow-up and a second biopsy if SG tissue is not present in the specimen.

Adolescent↗
PubMed1989

Comparative trial of cytarabine and thioguanine in combination with amsacrine or daunorubicin in patients with untreated acute nonlymphocytic leukemia: results of the L-16M protocol.

Ninety-six patients with de novo acute nonlymphocytic leukemia (ANLL) were randomized to receive either daunorubicin (50 mg/m2, IV) on days 1-3; cytarabine (Ara-C) (25 mg/m2, IV) bolus, followed by 160 mg/m2 as a continuous IV infusion daily for 5 days and 6-thioguanine (6-TG) (100 mg/m2 po) every 12 hr daily for 5 days (DAT); or amsacrine (190 mg/m2, IV) on days 1-3 with Ara-C and 6-TG at the above doses (AAT). Patients achieving complete remission (CR) then received two courses of consolidation therapy with the same combination that had induced remission but at slightly reduced total doses. Patients less than or equal to age 40 with an HLA-identical sibling donor underwent allogeneic transplantation, usually after consolidation therapy. The remaining patients were then randomized to receive either maintenance therapy (alternating cycles of vincristine/methotrexate, cyclophosphamide/6-TG, daunorubicin/hydroxyurea and Ara-C/6-TG) or no further treatment. Ninety-two patients were evaluable for response. Twenty-five of the 46 patients (54%) who received DAT and 32 of the 46 patients (70%) who received AAT achieved CR (p = 0.13). When patients were stratified by age, however, remission induction advantage with AAT became statistically significant (p = 0.03). Additionally, more patients achieved CR following one course of AAT than following one course of DAT (48% vs 28%, p = 0.03). Overall survival in the AAT group was improved as well (p = 0.01). Too few patients were randomized on the maintenance arm of the protocol to make interpretation meaningful. Non-hematologic toxicity was generally comparable in both arms. In conclusion, patients with de novo ANLL who received AAT had a higher remission incidence and slightly longer survival compared to patients who received DAT. Further investigation of this drug combination in untreated patients with ANLL is warranted.

Age Factors↗