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Biomedical subjects

M Cline

Publications and source records attributed to M Cline.

At least 19 recordsLinked to original sources
PubMed1997

Predicting protein structure using hidden Markov models.

We discuss how methods based on hidden Markov models performed in the fold-recognition section of the CASP2 experiment. Hidden Markov models were built for a representative set of just over 1,000 structures from the Protein Data Bank (PDB). Each CASP2 target sequence was scored against this library of HMMs. In addition, an HMM was built for each of the target sequences and all of the sequences in PDB were scored against that target model, with a good score on both methods indicating a high probability that the target sequence is homologous to the structure. The method worked well in comparison to other methods used at CASP2 for targets of moderate difficulty, where the closest structure in PDB could be aligned to the target with at least 15% residue identity.

Markov Chains↗
PubMed1996

Hormonal regulation of the normal breast.

The breast is a target organ for reproductive hormones but basic knowledge on hormonal effects is very poor. Available data indicate that the breast is regulated in a specific manner which is distinct from the endometrium and other target organs. It seems clear that the breast undergoes cyclic changes during the menstrual cycle and that in vivo there is a direct stimulatory action of progestogens on the breast. In surgically postmenopausal female macaques continuous combined estrogen/progestogen therapy was found to induce greater proliferation than estrogen alone.

Animals↗
PubMed1996

Rates of decline in lung function among subjects who restart cigarette smoking.

Several studies have demonstrated that smokers who are able to break the habit generally experience reductions in respiratory symptoms and improvement in pulmonary function; however, far less attention has been given to smokers who are unsuccessful in their attempts at quitting. Recent reports have suggested that these subjects (restarters) may have steeper rates of decline in pulmonary function than subjects never attempting to quit smoking. In this study, we compared rates of decline in FEV1 between restarters and subjects who remained current, ex-smokers, or never-smokers throughout the observation period. The results showed that, in both sexes, subjects who attempt to quit the habit and then restart have significantly steeper rates of decline in their FEV1 than subjects who continue smoking uninterrupted. Female restarters also have significantly steeper rates of decline in FEV1 than ex-smokers. These effects were independent of the amount smoked and respiratory diseases.

Adult↗
PubMed1992

Increased incidence of asthma in children of smoking mothers.

The relationship between parental smoking and both subsequent development of asthma and subsequent lung function (before age 12) was studied in more than 700 children enrolled before age 5. Children of mothers with 12 or fewer years of education and who smoked 10 or more cigarettes per day were 2.5 times more likely (95% confidence interval 1.42 to 4.59; P = .0018) to develop asthma and had 15.7% lower maximal midexpiratory flow (P less than .001) than children of mothers with the same education level who did not smoke or smoked fewer than 10 cigarettes per day. These relationships were independent of self-reported respiratory symptoms in parents. There was no association between maternal smoking and subsequent incidence of asthma or maximal midexpiratory flow among children of mothers with more than 12 years of education. It is concluded that children of lower socioeconomic status may be at considerable risk of developing asthma if their mothers smoke 10 or more cigarettes per day. It is speculated that recently reported increases in prevalence of childhood asthma may be in part related to the increased prevalence of smoking among less educated women.

Asthma↗
PubMed1991

The spectrum of molecular alterations in the evolution of chronic myelocytic leukemia.

DNA from 135 patients with chronic myelogenous leukemia (CML) at various clinical stages and Philadelphia (Ph1) chromosome positive acute lymphoblastic leukemia was investigated for alterations in a variety of proto-oncogenes which have been implicated in the evolution of CML from its chronic phase to blast crisis. The most common genetic change found in the evolution of typical Ph1 chromosome positive CML to blast crisis was an alteration of the p53 gene involving either a rearrangement, a deletion, or a point mutation in the coding sequence of the gene. Alterations of the p53 gene were found in the myeloid and the rare megakaryocytic variant of blast crisis but were absent in the lymphoid leukemic transformants. Gross structural alterations were seen in 11 of 54 (20%) of myeloid or unknown phenotypes of blast crisis and in only 1 of 44 chronic phase cases. Eight examples of mutations in the open reading frame of the p53 gene at codons 49, 53, 60, 140, 202, 204, 238, and 239 were observed in blast crisis patients. Mutations in the N-RAS gene were rare in typical blast crisis (2 of 27 cases) but were found in megakaryocytic and Ph1 negative myeloid blast crisis. We concluded that heterogeneous alterations in the p53 gene and occasionally in the N-RAS genes accompany the evolution of chronic phase CML to blast crisis.

Blotting, Northern↗
PubMed1990

Innervation territories for touch and pain afferents of single fascicles of the human ulnar nerve. Mapping through intraneural microrecording and microstimulation.

The peripheral distribution of the fibre content of individual ulnar nerve fascicles supplying skin and muscles of the hand in human volunteers was indirectly mapped by tracing the fields of projected sensation evoked by intraneural electrical microstimulation (INMS) and by tracing receptive fields delineated through intraneural recording of afferent impulse activity elicited by natural stimulation of end organs. Moderate intensity suprathreshold INMS, delivered in cutaneous fascicles, induced nonpainful sensations projecting to stereotyped and coherent areas of skin, the fascicular projected fields (FPFs). Fascicular receptive fields (FRFs) were mapped during microneurographic recording by determining the area of skin which, when activated by light tactile stimuli, elicited afferent neural discharges recorded intraneurally. It was found that at a given electrode position in a skin nerve fascicle, moderate intensity INMS induced nonpainful sensations projecting to a cutaneous field (FPF) that coincides with the FRF, while high intensity INMS induced painful sensations projecting within the cutaneous field of nonpainful sensations. Pain induced by INMS in muscle nerve fascicles was projected to the muscles innervated by that fascicle and, in most instances, to areas beyond the muscular receptive field. The study demonstrates that individual ulnar nerve fascicles, at wrist levels, subserve well-defined cutaneous territories in the hand, and that the area of skin covered by the sum of all ulnar fascicular receptive or projected fields matches the maximal possible cutaneous distribution of the ulnar nerve. Insights of practical relevance regarding clinical expression of fascicular nerve injuries are also brought up by this study.

Adult↗
PubMed1990

Sympathetic neural outflow directly recorded in patients with primary autonomic failure: clinical observations, microneurography, and histopathology.

We evaluated 2 patients with primary autonomic failure, without clinical peripheral neuropathy. One had primary autonomic failure alone (PAF), and the other had autonomic failure and multiple system atrophy (MSA). Direct intraneural recordings demonstrated a marked reduction of sympathetic efferent nerve impulse activity in the PAF patient. The patient with MSA had spontaneous bursts of sympathetic nerve impulses that confirmed the functional integrity of post-ganglionic sympathetic efferent neurons. Neurosecretory activity of these neurons correlated with the electrophysiologic findings. The PAF patient had markedly reduced supine norepinephrine (NE) levels that did not rise upon standing. The supine NE level in the MSA patient was normal. Morphometric study of biopsied sural nerve in the MSA patient showed that unmyelinated fibers were normal, whereas the nerve of the PAF patient showed clear evidence of past degeneration. We suggest that the primary preganglionic sympathetic defect in MSA releases viable postganglionic sympathetic efferents from central control. Decentralized postganglionic elements may fire spontaneously, thus activating peripheral effectors and providing potentially useful signs and symptoms for differential diagnosis.

Autonomic Fibers, Postganglionic↗
PubMed1989

Heat and mechanical hyperalgesia induced by capsaicin. Cross modality threshold modulation in human C nociceptors.

Quantitative thermal and mechanical algometry was studied in 4 human subjects exposed to various concentrations of capsaicin administered topically to the skin of the palm or forearm. Treated skin patches were assessed for changes in heat pain threshold and in mechanical pain threshold at various controlled temperatures. The results showed that: (1) in addition to heat hyperalgesia, capsaicin consistently induces overt mechanical hyperalgesia; (2) thermal and mechanical hyperalgesias are linearly dependent on the log of capsaicin dose; (3) mechanical hyperalgesia is increased by increasing skin temperature; (4) mechanical hyperalgesia is abolished by cooling the skin to a point about 10 degrees C below the threshold for heat pain, a temperature that does not impair touch or sharp pain sensation. These sensory effects of capsaicin are mediated by C fibres, since dissociated A fibre block established by compression-ischaemia does not abolish either spontaneous pain or mechanical hyperalgesia. In addition, abolition of mechanical hyperalgesia by cooling persists during A fibre block. Cooling thus appears to act directly, presumably decreasing hyperexcitability of the C nociceptor. Hyperalgesia is also transiently depressed for at least 30 min during the postischaemic period, well beyond the duration of paraesthesiae or overt hyperaemia. Sensory changes identical to those induced experimentally by capsaicin have been observed in patients with a particular variety of neuropathic pain (ABC syndrome) and have been termed polymodal hyperalgesia and cross modality threshold modulation (Ochoa, 1986; Ochoa et al., 1987). Based on these overall observations, it is postulated here that the sensory abnormalities induced by capsaicin and those observed in this particular variety of patients relate to primary hyperalgesia and share a common mechanism in that the excitable receptor membrane of polymodal C nociceptors behaves as if it 'misreads' temperature.

Biomechanical Phenomena↗
PubMed1987

Events on different chromosomes alter the genes for the two peptides of platelet-derived growth factor in an osteogenic sarcoma.

Platelet derived growth factor consists of dimers of partially homologous peptides (A and B) encoded by separate genes on different chromosomes. A clinically aggressive osteogenic sarcoma had both an amplified A-chain gene on chromosome #7 and a reduplication of all or part of chromosome #22 containing the B-chain (c-sis) gene. Other oncogenes on chromosomes #1, #2, #5, #6, #7, #8, #11, #12, #14, and #15 were not reduplicated or amplified. These observations are consistent with the hypothesis of autocrine stimulation of growth of some sarcomas in humans, and indicate that amplification and reduplication of related genes on different chromosomes can occur in tumors in vivo.

Chromosomes, Human, Pair 22↗
PubMed1987

Chemotaxis by Naegleria fowleri for bacteria.

Naegleria fowleri amebae demonstrated a chemotactic and chemokinetic response toward live cells and extracts of Escherichia coli and other bacterial species when experiments were performed using a blind-well chemotaxis chamber. The peptide N-formyl-methionyl-leucyl-phenylalanine acted as a chemokinetic rather than a chemotactic factor for N. fowleri amebae. Competition experiments in which nerve cell extracts or bacteria were placed on either side of the filter in chemotaxis chambers resulted in increased movement towards bacteria. A scanning electron microscopy study of the interaction of N. fowleri with different bacterial species confirmed that when the amebae were near ingestible bacteria they moved toward the bacteria by pseudopod formation. Naegleria fowleri appeared to respond to bacteria by three interrelated but distinct processes: chemokinesis, chemotaxis, and formation of food cups.

Amoeba↗
PubMed1986

Medical care costs of patients with AIDS in San Francisco.

This article reports on the findings of a study of medical care expenditures of persons with acquired immunodeficiency syndrome (AIDS) treated at San Francisco General Hospital in 1984. We found that mean charges per AIDS hospital admission were $9024, mean charges of patients with AIDS who received all their hospital inpatient and outpatient care at San Francisco General Hospital in 1984 ranged from $7026 to $23,425, and mean lifetime inpatient charges of patients with AIDS who died and who had received all their inpatient care at the hospital were $27,571. These latter charges were considerably lower than previously published estimates of lifetime direct medical care costs of patients with AIDS, and the possible reasons for the differences include much lower lifetime use of hospital services and somewhat lower cost per hospital day.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Adverse effects of pregnancy on multifocal eosinophilic granuloma.

An unusual case of a patient diagnosed as having the histiocytic proliferative disorder characterized by the lesion eosinophilic granuloma (histiocytosis X) is presented. Fifteen-year follow-up revealed a progression from a solitary eosinophilic granuloma of the bone to multifocal involvement of many body structures including the vulva, vagina, and cervix. This progression occurred after nine asymptomatic years and was temporally related to the patient's first pregnancy. After successful treatment and remission, rapid appearance and growth of observable genital lesions were noted during a second pregnancy. Pregnancy termination in the first trimester was advised due to signs of dissemination and local symptoms.

Abortion, Therapeutic↗
PubMed1986

Movement of Naegleria fowleri stimulated by mammalian cells in vitro.

Naegleria fowleri amebae, but not those of N. australiensis, N. gruberi, or N. lovaniensis, demonstrated enhanced motility when placed in proximity to mammalian cells. Amebae of nonpathogenic species of Naegleria, however, were more motile in cell culture medium than the amebae of N. fowleri. The locomotory response of highly pathogenic mouse-passaged N. fowleri amebae to nerve cells was greater than axenically cultured amebae. The enhanced mobility elicited by whole nerve cells or disrupted nerve cells was not directed migration but chemokinetic. Naegleria fowleri responded to disrupted neuroblastoma cells more vigorously than to disrupted African green monkey kidney (Vero) cells.

Animals↗
PubMed1985

Human alpha-lymphoblastoid interferon. A phase I study including pharmacokinetics and effects on hematologic stem cells (CFU-GMs).

Human alpha lymphoblastoid interferon (Wellferon) was administered to 33 patients in a phase I study. Patients received Wellferon intramuscularly every 12 hours for 14 doses in nine dosage levels ranging from 0.75 X 10(6) units to 50.0 X 10(6) units. Toxicity tended to be dose dependent and included fever/chills, malaise, hematologic toxicity, and digestive tract toxicity. Thirty X 10(6) u q 12 h was felt to be the maximum tolerated dose. Three partial responses (renal cell carcinoma, diffuse histiocytic lymphoma, Hodgkin's disease) were achieved. Interferon rapidly (2 to 3 hours after the initial injection) reached peak serum levels which varied generally with dose and exceeded 500 u/ml at the 30 and 50 X 10(6) u dosages. Multiple doses of interferon resulted in cumulative peak levels substantially higher than first dose levels (greater than 500 u/ml at dosages greater than 3 X 10(6) u/ml and greater than 1,500 u/ml at dosages greater than or equal to 18 X 10(6) u). Interferon given at high dosages persisted up to 10 days beyond the final injection. Despite hematologic toxicity, inhibition of CFU-GM was not seen.

Dose-Response Relationship, Drug↗
PubMed1983

Comparison of Naegleria fowleri and Naegleria gruberi cultivated in the same nutrient medium.

The human pathogenic amoeboflagellate Naegleria fowleri and the nonpathogenic species N. gruberi can be cultivated axenically but usually in different media. Naegleria fowleri 6088 has been adapted to grow in Balamuth H-4 medium, usually used to propagate N. gruberi nB81, and nB81 has been adapted to grow in supplemented Nelson's medium, usually used to propagate N. fowleri. N. gruberi nB81, grown in either medium, enflagellated 135 to 150 min after subculture to non-nutrient amoeba saline, whereas 6088 required 225 min. Naegleria gruberi nB81 grown in either medium was agglutinated by 100 micrograms concanavalin A/ml, whereas N. fowleri 6088 was not. Naegleria fowleri and N. gruberi grown in Nelson's medium became rounded to a greater extent upon chilling at 5 degrees C and remained rounded longer than Naegleria grown in Balamuth medium. The specificity of the surface antigens was an inherent characteristic of each species and not dependent upon the propagating medium, but Naegleria grown in Nelson's medium was agglutinated more reproducibly and more effectively by antiserum. N. gruberi was somewhat more resistant to acriflavine, actinomycin D, cycloheximide, or tetracycline than N. fowleri, regardless of the culture medium. Naegleria fowleri 6088 grown in Nelson's medium, however, was more resistant to actinomycin D, daunomycin, mithramycin, sulfamethoxazole, or tyrocidine than 6088 grown in Balamuth medium. There are limitations on the validity of comparisons of N. fowleri and N. gruberi based upon cultures grown in different media.

Agglutination Tests↗
PubMed1981

In vitro analysis of the contributions of adherent cell layer and recharging population to hemopoietic cell proliferation in long-term bone marrow cultures.

Cell proliferation in long-term suspension cultures of mouse bone marrow was studied. Bone marrow cells were maintained on irradiated or conventional non-irradiated semiallogeneic adherent feeder layers and the origin of the proliferating cells was investigated by using the unique T6 chromosome marker. In cultures containing irradiated feeder layers total cell numbers were less at the first week after "recharging," but the levels soon reached those of conventional non-irradiated cultures. At the first weeks after recharging, proliferating cells, maintained on conventional non-irradiated feeder layers, originated mainly from the adherent layer. The contribution of the recharging population to the proliferating cell population increased with time. In contrast, the proliferating cells grown on irradiated adherent layers originated mainly from recharging population from the first week after recharging. The origin of the nonadherent CFUs and their development in F1 hybrid mice and mice of syngeneic strains was also examined. The pluripotent stem cells grown on non-irradiated feeder layers were derived mainly from the adherent layer.

Animals↗
PubMed1981

Prevention of graft rejection following bone marrow transplantation.

Bone marrow transplantation from an HLA-identical sibling is increasingly used in the treatment of severe aplastic anemia. One major problem with this approach is graft rejection that occurs in 25%-60% of patients conditioned for transplantation with cyclophosphamide. At most transplant centers it has been difficult to accurately identify patients at high risk for graft rejection. We studied a conditioning regimen of cyclophosphamide (200 mg per kg) and low-dose total body irradiation (3 Gy; equivalent to 300 rad) in 23 consecutive unselected patients with aplastic anemia followed for a minimum of 6 mo. There was only one episode of graft rejection. Graft-versus-host disease and interstitial pneumonitis were not increased by the more intensive conditioning regimen. Actuarial survival was 61% at 1 yr and 49% at 2.5 yr. Cyclophosphamide and low-dose total body irradiation is an effective conditioning regimen in patients with aplastic anemia. It may be particularly useful when accurate predictive tests of graft rejection are not available as is the case in most transplant centers.

Actuarial Analysis↗