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Biomedical subjects

M Miller

Publications and source records attributed to M Miller.

At least 37 records · Page 2Linked to original sources

Comparison of in vitro tests for evaluation of passive transfer of immunoglobulins in giraffe (Giraffa camelopardalis).

Serum samples from captive giraffe (Giraffa camelopardalis) were tested to assess passive transfer of immunoglobulins using in vitro methods developed for domestic ruminants. Estimated immunoglobulin levels were compared using five tests (protein electrophoresis, total protein refractometry, zinc sulfate turbidity, glutaraldehyde coagulation, and sodium sulfite turbidity). A linear relationship was observed among total protein, gamma globulin (electrophoretic measurement), and immunoglobulin level based on spectrophotometric measurement of zinc sulfate turbidity. Nonquantitative assays also demonstrated statistical correlation with the quantitative methods. Using criteria similar to those established for domestic species, cutoff values for failure of passive transfer (FPT) were established for these tests in neonatal giraffe: 1) total protein <6.0 g/dl; 2) gamma globulin < 0.5 g/dl; 3) estimated immunoglobulin level < 1,000 mg/dl (zinc sulfate turbidity); 4) glutaraldehyde coagulation test negative; or 5) no visually detectable turbidity in 16% sodium sulfite or Bova-S negative. Retrospective examination of the medical histories showed a strong statistical association between animals designated as having FPT and those that were removed from their dams based on clinical assessment to be hand-reared. Application of these tests in the field should allow earlier detection and intervention for FPT in neonatal giraffe.

Animals

Treatment of 70(+)-year-olds with recurrent major depression. Excellent short-term but brittle long-term response.

The authors compared response rates, by age (60-69 vs. 70+), to acute, continuation, and 1-year maintenance depression treatment. Patients (N = 180) received open combined treatment with nortriptyline (NT)/placebo and interpersonal psychotherapy (IPT). Patients who recovered then entered randomized, double-blind maintenance treatment with NT or placebo or received maintenance monthly IPT (combined with NT or placebo). Comparison of time-to-remission and recovery and absolute rates of remission, relapse, recovery, and recurrence yielded similar times to/rates of remission and recovery; however, older patients had far more recurrence during the first year of maintenance therapy. Although responses to acute and continuation treatment with combined NT and psychotherapy were similar, the older group had more recurrence in the first year of maintenance. Continuation of combined medication and psychotherapy may represent the best long-term treatment.

Age Factors

Evolutionary conservation of a testes-specific proteasome subunit gene in Drosophila.

Proteasomes are large multisubunit particles that act as the proteolytic machinery for the ubiquitin-dependent proteolytic pathway. The core of this complex, the 20S proteasome, is made up of seven alpha-type and seven beta-type subunits, arranged in an (alpha1-alpha7)(beta1-beta7)(beta1-beta7)(alpha1-al pha7) configuration. Previous work had shown that there exist alternative isoforms of the Drosophila melanogaster alpha4-type subunit, encoded by two distinct genes, alpha4t1_dm and alpha4t2_dm, and that these are expressed exclusively in the germline of the testes. We sought to investigate the evolutionary conservation of this phenomenon by screening for orthologs of the alpha4-type gene family in the distantly related Drosophila species, D. virilis. We isolated the D. virilis orthologs of the somatically expressed gene, alpha4_dm, and the testes-specific gene, alpha4t2_dm. We failed to find an ortholog of the other testes-specific gene, alpha4t1_dm. The alpha4_dv gene maps to the X chromosome at 12A-C, its product shares 90% amino acid identity with alpha4_dm, and it is expressed at high levels in both males and females. The other gene, alpha4t_dv, encodes a protein most similar to the testes-specific alpha4t2_dm proteasome subunit (59% a.a. identity), and it maps to position 27 on chomosome 2. The expression of the alpha4t_dv gene is testes-specific, like that of alpha4t2_dm. The existence of testes-specific alpha4-type subunits in two widely diverged subgenera of Drosophila suggests that these subunit isoforms have important functional roles in spermatogenesis.

Amino Acid Sequence

Mode of receptor binding and activation by plasminogen-related growth factors.

Hepatocyte growth factor/scatter factor (HGF/SF) and macrophage stimulating protein (MSP) are plasminogen-related kringle proteins that lost serine protease domain enzymatic activity and became ligands for cell surface tyrosine kinase receptors. They are activated by cleavage to disulfide-linked alphabeta chains. Surprisingly, despite structural similarities, the high affinity receptor binding regions of the two proteins are different: alpha chain for HGF, and beta chain for MSP. We propose that after cleavage exposes a beta chain binding site (high affinity for MSP, low affinity for HGF), monomeric ligand induces receptor dimerization and activation via alpha and beta chain binding sites of different affinity.

Animals

Examination for heat-labile, heat-stable, and Shiga-like toxins and for the eaeA gene in Escherichia coli isolates obtained from dogs dying with diarrhea: 122 cases (1992-1996).

OBJECTIVE: To examine Escherichia coli isolates obtained from dogs dying with diarrhea for heat-labile, heat-stable, and Shiga-like toxins and for the eaeA gene, which is associated with attaching and effacing lesions. DESIGN: Retrospective study. ANIMALS: 122 dogs. PROCEDURE: E coli isolates were tested by means of dot-blot hybridization of DNA extracts of cultured bacteria. Medical records of dogs from which E coli isolates with virulence genes had been isolated were examined, and histologic findings and evidence of intercurrent bacterial and viral infections were recorded. RESULTS: None of the E coli isolates obtained from these dogs produced heat-labile, heat-stable, or Shiga-like toxins; however, E coli isolates from 44 of 122 dogs were found to have the eaeA gene. Histologically, multifocal bacterial adherence to the epithelium and epithelial necrosis and detachment were seen in colonic specimens from 20 of 44 (45%) dogs. Escherichia coli was the sole pathogen identified in 15 of 44 (34%) dogs. Intercurrent pathogens, including canine parvovirus (n = 19), Clostridium perfringens (8), rotavirus (5), hookworms (3), coccidia (3), and Salmonella agona (1), were identified in the remaining 29 (66%) dogs. CLINICAL IMPLICATIONS: Attaching and effacing E coli can be a primary or secondary pathogen in dogs with diarrhea. Antibiotic treatment is indicated in dogs with diarrhea because of the possibility that it is primarily bacterial in origin and because, even if it is primarily viral in origin, there may be secondary bacterial infection.

Adhesins, Bacterial

Menaquinone-7 in the reaction center complex of the green sulfur bacterium Chlorobium vibrioforme functions as the electron acceptor A1.

Photosynthetically active reaction center complexes were prepared from the green sulfur bacterium Chlorobium vibrioforme NCIMB 8327, and the content of quinones was determined by extraction and high-performance liquid chromatography. The analysis showed a stoichiometry of 1.7 molecules of menaquinone-7/reaction center. No other quinones were detected in the isolated reaction centers, whereas membrane preparations also contained chlorobiumquinone. The possible involvement of quinones in electron transport was investigated by electron paramagnetic resonance (EPR) spectroscopy. A highly anisotropic radical was detected by Q-band EPR spectroscopy in both membranes and isolated reaction centers following dark reduction with sodium dithionite and photoaccumulation at 205 K. At 34 GHz, the EPR spectrum is characterized by a g tensor with gxx = 2.0063, gyy = 2.0052, gzz = 2.0020 and delta B of 0.7 mT, consistent with its identification as a quinone. This spectrum is highly similar in terms of g values and line widths to photoaccumulated A1- in photosystem I of Synechococcus sp. PCC 7002. The results indicate that menaquinone-7 in the green sulfur bacterial reaction center is analogous to phylloquinone in photosystem I.

Amino Acid Sequence

Ethnic cluster of HTLV-I infection in Israel among the Mashhadi Jewish population.

A high prevalence of human T-lymphotropic virus type I (HTLV-I) infection among Israeli Jews was previously reported. In the present study, screening for HTLV-I of Israeli Jews was expanded to 10 ethnic groups. HTLV-I antibodies were tested by the particle agglutination assay, ELISA, and by Western blot as a confirmatory method. The HTLV-I proviral genome was tested by nested PCR with tax primers (SK43/SK44 and Tr101/Tr102). The PCR tests were carried out in all seropositive subjects and the seronegative family members of the seropositives subjects in the Iranian population. Sixty-eight of the 1,679 subjects (4.1%) were found to be seropositive. The Jews originating from Mashhad had the highest infection rate of 60/306 (20%). Of the 479 Iranian non-Mashhadi Jews, 6 (1.3%) were seropositive. Of the 894 non-Iranian Israelis, only 2 (0.2%) were seropositive. HTLV-I proviral DNA was found in the peripheral blood lymphocytes of 66 out of 68 seropositive subjects and 6 out of 75 seronegative subjects. Sixty out of 123 (49%) Mashhadi Jews and 8 out of 14 (57%) non-Mashhadi Iranian Jews were PCR-positive. Three out of three seropositive non-Iranian Israelis were PCR positive. One non-Iranian Israeli (who originated from Ukraine) without family connections to the Iranian Jews was also PCR-positive. One hundred eighteen saliva samples (84 from subjects of Mashhadi origin, 31 from Iranian origin, and 4 of other origins) were also screened. Antibodies for HTLV-I were found in 23 out of 46 saliva samples from the individuals with particle agglutination (PA) and/or PCR-positive findings in blood. Twenty out of 23 PA-positive saliva samples also contained the proviral DNA. It is concluded that HTLV-I infection in Israel is mainly limited to Jews originating from Iran (most of them from Mashhad) and their family members.

Adolescent

Missed opportunities for cervical cancer screening of HMO members developing invasive cervical cancer (ICC).

OBJECTIVE: To identify potential missed opportunities and to suggest interventions for cervical cancer screening in members of a prepaid health plan by examining the membership histories and medical records of women who had no Pap smear performed in the 3 years prior to the diagnosis of ICC. METHODS: Medical records of all 642 members of a prepaid health plan developing ICC during the period from 1988 to 1994 were reviewed and details of patient interaction with the health care system were abstracted. Assessment of screening history and history of clinic visits was limited to the period 36 months prior to diagnosis, but excluded the last 6 months prior to diagnosis, so as to avoid including smears or visits which were part of the evaluation that led to the recognition of ICC. RESULTS: Of women developing ICC, 384/642 (60%) had not had a smear in the period from 36 months to 6 months preceding the diagnosis. Of these 384 unscreened women, 241 (63%) had been insured by our HMO for at least 30 of the 36 months prior to diagnosis. Contact with the medical system in one of the primary care outpatient clinics was documented in 180/241 (75%) of these long-standing members during the specified period. Considering only Internal Medicine and Family Practice clinic visits, 169/241 (70%) had been seen at least once and 101/241 (42%) had been seen 3 or more times. CONCLUSION: Most long-standing HMO members developing ICC without benefit of recent Pap smear screening were seen in primary care outpatient clinics in the 3 years preceding their diagnosis.

Female

Treatment of rats during pubertal development with 2,3,7,8-tetrachlorodibenzo-p-dioxin alters both signaling kinase activities and epidermal growth factor receptor binding in the testis and the motility and acrosomal reaction of sperm.

Different doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (0.1, 1, 5, and 10 micrograms/kg body wt) were administered i.p. to 21-day-old male Sprague-Dawley rats. Control animals received the same volume of the vehicle (acetone:corn oil, 1:19). Body weight and daily food intake were recorded during the 90-day time course of the study. Random samples of five rats were sacrificed at 34, 49, 62, and 90 days of age. Epidermal growth factor receptor (EGFR) in whole testis was measured, as were the activities of c-Src kinase, protein tyrosine kinase (PTK), mitogen-activated protein 2 kinase (MAP2K also termed as Erk2), protein kinase A (PKA), and protein kinase C (PKC). Testicular tissue from 90-day-old rats was evaluated for histopathology, and sperm numbers in whole testis were counted to estimate daily sperm production. The motility of sperm in the vas deferens and caudal segments of the epididymis of 90-day-old rats was measured by computer assisted sperm analysis (CASA) and the function of the sperm was tested by assessment of acrosome reactions. A dose of 10 micrograms/kg resulted in testicular atrophy and histopathologic examination revealed a decrease in the diameter of the seminiferous tubules. Sertoli cell nuclei were clearly seen, but the spermatogonial population was totally absent. Lower doses of TCDD did not affect testicular histology, but doses as low as 1 microgram/kg significantly decreased testicular sperm numbers and affected some sperm functions (motility parameters and acrosome reactions) in 90-day-old rats. Significant decreases in EGFR were found in 34-day-old rats and this effect on EGFR was sustained until the end of the experiment (90 days). Although TCDD significantly increased c-Src kinase activity in immature and mature rats, opposite effects of TCDD on activities of PTK, PKA, and PKC were found in 34-day-old rats vs 49-, 62-, and 90-day-old rats. When 10 micrograms TCDD/kg was administered to 21-day-old rat, 24-h after c-Src kinase inhibitor geldanamycin, there was no testicular atrophy and no change in the daily sperm production was found. These findings provide evidence for involvement of Src kinase signaling and EGFR in the mechanism by which TCDD disrupts testicular development and subsequently affects testis function.

Acrosome

Linkage of the apo CIII microsatellite with isolated low high-density lipoprotein cholesterol.

To evaluate whether a highly polymorphic microsatellite region within intron 3 of the apolipoprotein (apo) CIII gene is linked to the isolated low HDL-C phenotype, we studied eight unrelated probands (mean HDL-C = 10+/-5 mg/dl) and 157 biological family members. After PCR amplification of genomic DNA and denaturing polyacrylamide gel electrophoresis, 26 alleles were identified in this microsatellite including 9 alleles heretofore unreported. Quantitative sib-pair linkage analysis demonstrated strong evidence of linkage between the isolated low HDL-C phenotype and the apo CIII microsatellite region (P = 0.007). The microsatellite was also linked to apo AI (P = 0.001), the primary apolipoprotein of HDL-C. Therefore, this highly polymorphic microsatellite region is a potentially important marker in the genetic evaluation of the isolated low HDL-C phenotype.

Adolescent

The use of unproven methods of treatment by cancer patients. Frequency, expectations and cost.

The use of unproven therapies is of concern for a number of reasons, including the lack of scientific evidence of support them, their potential financial costs and the possibility of interference with conventional treatment. This study explored the prevalence, predictors and experiences of unproven therapy use by cancer patients attending an oncology clinic at an Australian teaching hospital. A questionnaire was administered to patients whilst they were waiting for a consultation with their oncologist. A total of 173 patients were invited to participate, and 156 consented to complete the survey (90%). Over half the patients (81, 52%) had used at least one unproven therapy since their diagnosis, and 28% had used three or more. Patients most commonly practised mediation/relaxation, changed their diet and used multi-vitamins. Most expected that the therapies would aid their conventional treatments and make them feel more in control of their situation. Benefits reported were largely psychological, such as an increased sense of control or a reduction in anxiety. Younger patients, those with early stage or advanced metastatic disease and those who had used unproven therapies prior to developing cancer were more likely to use unproven therapies. Health professionals involved in the care of cancer patients should be prepared to discuss the use of unproven therapies and try to identify and deal with unmet needs to help patients to cope with their illness.

Adult