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Biomedical subjects

M Till

Publications and source records attributed to M Till.

At least 55 records · Page 3Linked to original sources
PubMed1994

The inadequacy of standard treatment of dysplasias in a woman with acquired immune deficiency syndrome.

The current state of knowledge regarding the gynecologic care of HIV-infected women is in its infancy. Standard algorithms are not valid. We present an example of the inadequacy of routine surveillance and treatment methods in these patients. Practitioners should maintain a high index of suspicion for multifocal genital dysplasias and individualize patient follow-up and therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Detection of HIV-1 DNA and messenger RNA in individual cells by PCR-driven in situ hybridization and flow cytometry.

Human immunodeficiency virus type-1 (HIV-1) DNA and messenger RNA sequences in both cell lines and blood obtained directly from HIV-1-infected patients were amplified by polymerase chain reaction and hybridized to fluorescein-labeled probes in situ, and the individually labeled cells were analyzed by flow cytometry. After flow cytometric analysis, heterogeneous cell populations were reproducibly resolved into HIV-1-positive and -negative distributions. Fluorescence microscopy showed that the cellular morphology was preserved and intracellular localization of amplified product DNA was maintained. Retention of nonspecific probe was not observed. Analysis of proviral DNA and viral messenger RNA in cells in the blood of HIV-1-infected patients showed that the HIV-1 genome persists in a large reservoir of latently infected cells. With the use of this technique it is now possible to detect single-copy DNA or low-abundance messenger RNA rapidly and reproducibly in a minor subpopulation of cells in suspension at single-cell resolution and to sort those cells for further characterization.

Base Sequence↗
PubMed1993

Analysis of human immunodeficiency virus-infected tissues by amplification and in situ hybridization reveals latent and permissive infections at single-cell resolution.

Latent and productive viral infections are at the extremes of the spectrum of virus-cell interactions that are thought to play a major role in the ability of such important human pathogens as human immunodeficiency virus (HIV) to elude host defenses and cause disease. The recent development of PCR-based methods to amplify target sequences in individual cells in routinely fixed tissues affords opportunities to directly examine the subtle and covert virus-cell relationships at the latent end of the spectrum that are inaccessible to analysis by conventional in situ hybridization techniques. We have now used PCR in situ with in situ hybridization to document latent and permissive HIV infection in routinely fixed and paraffin-embedded tissue. In one of the first specimens we examined, a tumor biopsy from an HIV-infected individual, we found many of the lymphocytes and lymphocytes infiltrating the tumor had HIV DNA that was detectable only by PCR in situ. The fraction of positive cells varied regionally, but there were foci where most of the cells contained HIV DNA. Most of these lymphocytes and macrophages are latently infected, as we could detect HIV RNA in fewer than one in a thousand of these cells. We also detected HIV RNA, surprisingly, in 6% of the tumor cells, where the number of copies of viral RNA per cell was equivalent to productively infected cell lines. The alternative states of HIV-gene expression and high local concentration of latently infected lymphocytes and monocytes revealed by these studies conceptually supports models of lentiviral pathogenesis that attribute persistence to the reservoir of latently infected cells and disease to the consequences of viral-gene expression in this population. The magnitude of infection of lymphocytes documented in this report is also consistent with the emerging view that HIV infection per se could contribute substantially to depletion of immune cells in AIDS.

Adenocarcinoma↗
PubMed1993

Schistosomiasis and cervical cancer in Ghana.

OBJECTIVE: To discover a possible association between schistosomiasis and cervical dysplasia and/or cervical cancer in Ghana, West Africa. METHOD: Two groups of 24 subjects each were identified, one group from a schistosomiasis-endemic area and a control group from a non-endemic area. Random cervical biopsies, cervical cytology and human papilloma virus (HPV) DNA testing were performed on all subjects. Demographic data were analyzed using Student's t-test. Histologic and DNA findings were analyzed using Fisher's exact test. RESULTS: From the endemic area, 46% of subjects had histologic evidence of schistosomiasis infection of the cervix. No evidence of dysplasia or cancer on cervical cytology was noted in this group. Mild dysplasia was noted in random cervix biopsies in one patient, and 8 patients had evidence of HPV infection of the cervix. No patient from the non-endemic area had cytologic or histologic evidence of cervical dysplasia or cancer. Eleven subjects in this group had evidence of HPV infection. CONCLUSION: This study does not reveal an association between cervical schistosomiasis and cervical dysplasia or cervical cancer on cytology or histology. Both study groups demonstrated a high degree of infection with HPV, however. It may be the HPV and not the schistosomiasis which is responsible for the development of uterine cervix cancer.

Adult↗
PubMed1993

[Multiple acyl-CoA dehydrogenase deficiency. Report of 2 siblings].

The authors report on two siblings with a multiple acyl-CoA dehydrogenase deficiency. The first child died from a Reye's syndrome when he was 9 month-old. The diagnosis was made in the neonatal period in his brother. Early treatment with glucose and carnitine should prevent acute attacks.

Acyl-CoA Dehydrogenases↗
PubMed1993

[Postoperative management with pulsed high frequency electromagnetic energy. A clinical study of 38 patients with rhinoseptoplasty].

The effect of high frequent electromagnetic radiation pulse (PHEE) on the resorption of postoperative hematomas was investigated in 38 patients who underwent rhinoseptoplasty. 18 patients were treated twice a day using a diapulse equipment, whereas the patients in the control group did not get radiation. In the radiated patients, measurements of the infraorbital hematoma showed accelerated resorption-contrary to the course of the supraorbital hematoma. Diapulse radiation also prevented the enlargement of hematomas that usually proceeds until the third postoperative day. Results of undiminished resorption in the upper eyelid may be caused by inadequate penetration of PHEE or a methodical mistake in the analysis. Additionally, patients treated with PHEE needed a shorter course of postoperative antiphlogistic treatment when compared to the control group. The treatment might further be improved by preoperative use of PHEE or additional radiation of the liver, spleen, and adrenal gland. The results of our investigation showed the improvement of wound healing by using PHEE.

Electromagnetic Fields↗
PubMed1991

Balanced complex chromosomal rearrangements with more than four breakpoints: report of a new case.

Congenital complex chromosomal rearrangement (CCR) compatible with life are rare in man. We report on a new case of apparently balanced CCR in a 30-month-old boy with mental retardation and minor anomalies. This CCR consists in a 3-way reciprocal translocation (2;3;16) and an insertion (6;7), as it was analyzed by different banding and high resolution techniques. It involves 6 breakpoints: 2q11, 13q12, 16p11, 6p21.3, 7q21.3 and 7q35.

Abnormalities, Multiple↗
PubMed1991

Phase I immunotoxin trial in patients with B-cell lymphoma.

Fifteen patients with refractory B-cell lymphoma were treated in a Phase I dose escalation clinical trial with a highly potent immunotoxin consisting of the Fab' fragment of a monoclonal anti-CD22 antibody (RFB4) coupled to chemically deglycosylated ricin A chain. All patients had low, intermediate, or high grade non-Hodgkin's lymphoma. The immunotoxin was administered i.v. in two to six doses at 48-h intervals. The peak serum concentration and the t1/2 were not dose dependent among patients and averaged 1.3 micrograms/ml and 86 min, respectively. Three patients made antibody against A chain, and a fourth made antibody against both A chain and mouse immunoglobulin. Antibody responses were low (less than or equal to 85 micrograms/ml) in three patients and were not detected until 1 mo after treatment. The maximum tolerated dose of the immunotoxin was 75 mg/m2. Dose-related toxicities included vascular leak syndrome, fever, anorexia, and myalgia. Dose-limiting toxicities included pulmonary edema and/or effusion, expressive aphasia, and rhabdomyolysis (resulting in reversible kidney failure). There was no evidence of liver dysfunction. Partial responses were achieved in 38% of evaluable patients, and in those patients who had greater than 50% CD22+ tumor cells, 50% of the patients achieved a partial response. Clinical responses were not related to tumor grade and were generally transient, lasting between 1 and 4 mo.

Adult↗
PubMed1991

High-level gentamicin resistance in Enterococcus faecalis bacteremia.

In a retrospective analysis, patients with bacteremia due to Enterococcus faecalis with and without high-level gentamicin resistance (GRE; MIC greater than 2000 micrograms/ml) were compared. Bacteremic patients with GRE (n = 32) had significantly higher rates of nosocomial acquisition and bladder catheterization, longer hospitalizations, and more frequent prior treatment with cephalosporins than did bacteremic patients without high-level resistance (n = 19). Overall mortality was significantly associated with septic shock, high-risk source (intraabdominal, wound, respiratory tract, multiple, unknown), and polymicrobial bacteremia. Higher mortality was observed in GRE bacteremia (47%) than in bacteremia without high-level resistance (37%), but this difference was not statistically significant. For patients with monomicrobial bacteremia, low-risk source (genitourinary tract, intravascular), or treatment with antibiotics appropriate for the enterococcus, higher mortality with GRE bacteremia approached statistical significance. These results suggest that high-level resistance adversely affects survival with a pure E. faecalis bacteremia or low-risk bacteremic source. Also, response to antibiotic therapy may be diminished by high-level resistance.

Adult↗
PubMed1990

Naloxone-insensitive modulation of gastric acid output by [D-Met2,Pro5]enkephalinamide in rats.

Studies from our laboratory have previously shown that two opioid agonists (morphine and [D-Met2,Pro5]enkephalinamide) aggravate, whereas naloxone inhibits cold-restraint stress-induced ulceration in rats. In the present study the effects of these substances were examined using the Shay-model. Contrary to expectations, both naloxone and the opioid agonists decreased gastric acid output. Naloxone in combination with either opioid agonist failed to reverse their inhibitory action. Thus the secretory activity of the stomach may be modulated by opioids in both naloxone-reversible and irreversible ways.

Animals↗
PubMed1989

The epitope specificity and tissue reactivity of four murine monoclonal anti-CD22 antibodies.

The CD22 antigen is expressed on the surface of normal human B cells and some neoplastic B cell lines and tumors. Previous cross-blocking studies using a panel of monoclonal anti-CD22 antibodies have defined four epitope groups, termed A-D. In the present studies, we have further dissected the epitopes recognized by four monoclonal anti-CD22 antibodies using immunoprecipitation and cross-blocking techniques, immunofluorescence analyses with a variety of cell lines, and immunoperoxidase analyses of 36 normal human tissues. Two of the antibodies, HD6 and RFB4, have been described previously, and two, UV22-1 and UV22-2, are described in this report. Our studies indicate that the four monoclonal antibodies show unexpected complexities in their reactivity with CD22+ and CD22- cells and their reactivity with solubilized CD22 molecules. The four antibodies, which recognize epitopes defined previously as CD22-A and CD22-B, further subdivide these epitope clusters into four determinants, A1, A2, B1, and B2. Furthermore, only two of the antibodies, RFB4 and UV22-2, are B cell-specific. In summary, our data indicate that RFB4 and UV22-2 would be the antibodies of choice for constructing immunotoxins to treat B cell tumors.

Animals↗
PubMed1988

Evaluation of four CD22 antibodies as ricin A chain-containing immunotoxins for the in vivo therapy of human B-cell leukemias and lymphomas.

Ricin A chain-containing immunotoxins (IT-As) specific for the human B-cell antigen, CD22, were prepared from 4 monoclonal antibodies (MAbs) or their Fab' fragments: RFB4, HD6, UV22-I and UV22-2. The ITs were tested for their ability to kill cells from the Burkitt lymphoma line, Daudi, the pre-B-cell leukemia line, NALM-6, and the myeloma cell line, ARH-77. Daudi expresses high levels of CD22, whereas NALM-6 and ARH-77 express low levels of CD22. The IgG-RFB4-A was highly toxic to all 3 cell lines; it killed 50% of the Daudi cells at a concentration of 1.2 x 10(-12) M and 50% of NALM-6 and ARH-77 cells at concentrations of 1.5 to 2.1 x 10(-11) M. IgG-RFB4-A was 10-30 times more toxic to Daudi cells than were the IgG-As constructed from the other 3 CD22 MAbs and 10 times more toxic than ricin itself. IT-As constructed from the Fab' fragments of the 4 CD22 antibodies were 2 to 5 times less toxic to Daudi cells than their IgG-A counterparts. Fab'-RFB4-A was twice as toxic to Daudi cells as ricin, whereas the other Fab'-As were about 7 times less toxic than ricin. Scatchard analyses of the binding of the radio-iodinated antibodies to Daudi cells showed that the intact RFB4 antibody bound 3-10 times more strongly than the other antibodies, whereas the Fab'-RFB4 bound 1.2 to 3.5 times more strongly than the Fab' fragments prepared from the other antibodies. Thus, the potent cytotoxic activity of the RFB4-As appears to derive, in part, from their superior binding affinity. Prior studies have shown that UV22-I and HD6 cross-react with certain normal human tissues lacking cells of B-cell lineage, whereas UV22-2 and RFB4 are B-cell-specific. This fact, together with its superior potency as an IT-A, suggests that RFB4 is the antibody of choice for preparing Fab'-As or IgG-As for in vivo therapy of human B-cell leukemias and lymphomas.

Animals↗
PubMed1988

Effect of [D-Met2,Pro5]enkephalinamide on gastric ulceration and transmucosal potential difference.

The effects of [D-Met2,Pro5]enkephalinamide, morphine and naloxone have been examined in two different models of experimentally elicited gastric mucosal lesions. One of them was the classic cold-restraint stress-induced ulceration. The other was a less frequently applied procedure, involving the measurement of decreases in the transmucosal potential difference, which is also a sensitive indicator of mucosal damage. The opioid agonists studied, [D-Met2,Pro5]enkephalinamide and morphine, aggravated, whereas naloxone, the pure opiate antagonist, mitigated the lesions in both models. The protective action of naloxone points to an eventual role of endogenous opioids in the generation of these types of mucosal lesions. Morphine is selective ligand of mu-opiate receptors. The enkephalin analogue, however, binds to both mu- and delta-receptors. Therefore, the potent pro-ulcerogenic action of the enkephalin analogue indicates that both the mu- and delta-receptors were involved in these models of experimental gastric lesions. The clarification of the eventual role of kappa-receptors requires further experimental work with a selective ligand of this subtype of opiate receptors.

Analgesics↗
PubMed1988

Evaluation of ricin A chain-containing immunotoxins directed against CD19 and CD22 antigens on normal and malignant human B-cells as potential reagents for in vivo therapy.

Ricin A chain-containing immunotoxins (IT-As) specific for the human B-cell antigens, CD22 and CD19, were constructed using the monoclonal antibodies, HD6 and HD37, respectively. IT-As were prepared by coupling intact antibodies, F(ab')2, or Fab' fragments to native or chemically deglycosylated ricin A chain. The IT-As were then evaluated for cytotoxicity to normal and neoplastic human B-cells in vitro with the major objective of appraising their suitability for in vivo therapy of human B-cell tumors. The IT-As prepared with both the HD6 and HD37 antibodies were specifically toxic to normal B-cells and to most of the neoplastic B-cell lines tested. However, the IT-As prepared from HD6 were generally more potent than those prepared from HD37. On Daudi cells, to which the two antibodies bound in similar numbers and with similar affinities, IT-As prepared with intact HD6 antibody or its Fab' fragment were 10-fold and 1.5- to 4-fold more potent, respectively, than the corresponding HD37 IT-As. The IT-As constructed from intact HD6 antibody and native or deglycosylated A chain reduced protein synthesis in Daudi cells by 50% at a concentration of 1.2 X 10(-11) M indicating that they were only 5-fold less toxic to the cells than ricin itself. Intact HD37 IT-As produced equivalent inhibition of protein synthesis at 1.5 X 10(-10) M. With both antibodies, IT-As constructed from the Fab' fragments were 10- to 20-fold less potent than their intact antibody counterparts. Different neoplastic B-cell lines varied in sensitivity to the IT-As. In most cases, their sensitivity correlated with the levels of CD19 and CD22 antigens expressed. Neither HD6 nor HD37 IT-As affected the ability of normal human bone marrow cells to form granulocyte-macrophage colony-forming units in soft agar, suggesting that both antigens are absent from these progenitor cells. Examination of sections of frozen human tissues using immunoperoxidase staining procedures indicated that the antibodies did not bind to a panel of normal tissues lacking B-lymphocytes. These results suggest that HD6 and HD37 IT-As are candidates for in vivo therapy in humans with certain B-cell tumors. However, HD6 IT-As are more potent, reduce protein synthesis more completely, and hence appear to be the ITs of choice for treating tumors expressing the CD22 antigen.

Antigens, CD↗