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Biomedical subjects

D Keith

Publications and source records attributed to D Keith.

15 recordsLinked to original sources

Human T-cell leukemia virus type-I/II (HTLV-I/II) serologic testing: the importance of assaying for the full complement of viral antigens.

Seventy-one Japanese adult T-cell leukemia (ATL) patients and 411 Japanese asymptomatic patients from HTLV-I endemic regions of southern Japan were found to be seropositive by radioimmunoprecipitation assay (RIPA). Of these 482 positive controls, 62% of ATL patients and 67% of the asymptomatic seropositive patients were found to harbor antibodies to p40x. Additionally, 333 preselected Japanese blood donors who were identified as seropositive by particle agglutination (PA) assay were further tested for antibodies to HTLV-I/II gene encoded envelope (env) or group specific antigens (gag) by means of enzyme-linked immunosorbent assay (ELISA) and RIPA. Concordance between ELISA and RIPA was noted in 318 samples (92.5%). Discordance between ELISA and RIPA was observed in 15 sera (7.5%)--2 were seropositive by ELISA and seronegative by RIPA and 13 were seronegative by ELISA and seropositive by RIPA. Seven of these 13 samples (53.8%) contained antibodies to p40x by RIPA and may represent ELISA false negatives on the basis of both clinical and laboratory data. Current HTLV-I/II ELISA kits may yield false negative results. Additional research into the development of rapid detection cost-efficient assays that test for the full compliment of viral antigens is needed.

Agglutination Tests

Pregravid weight, gestational weight gain and current weight of women delivered of twins.

To determine whether large gestational weight gains result in higher maternal body weight within two years post-partum, we administered an anonymous survey to 423 mothers of twins at the Annual Twinsday Festival in Twinsburg, Ohio, in 1989 and 1990. Data collected included pregravid and current weight, age and parity, gestational weight gain and length of gestation. Data were grouped by patient age (18-24 years, 25-34 years and 35-44 years), parity (primipara or multipara) and length of gestation as preterm (less than 37 weeks) and term (greater than or equal to 37 weeks). Statistical analysis included paired t-tests, unpaired t-tests and chi-square as appropriate. Except for multiparas in the oldest age category, the mean current weight was higher than pregravid weight for each age and age/parity category. Comparison across age categories showed in pattern of increasing pregravid weight with increasing age for the total study sample (all women) and for primiparas; among multiparas, this trend was not as evident. Our findings suggest that large weight gains in twin gestations do not result in higher maternal body weight within two years postpartum. Such gains are associated with better intrauterine growth and should be considered when formulating weight gain recommendations for twin gestations.

Adolescent

Trigeminal facial pain: a model of peptides and monoamines in intracerebral cerebrospinal fluid.

A biochemical model of chronic trigeminal facial pain with elevated substance P (SP) and co-dysfunctional dopamine (DA), norepinephrine (NE) and purinergic systems is proposed. The serotonergic system is hypoactive as judged by low 5 hydroxyindoleacetic acid (5HIM). In distinction, intracerebral opioids may not be dysfunctional in facial pain as measured by normal levels of beta endorphin (BE). The neuropeptides somatostatin (SOM), cholecystokinin (CCK), met and leu-enkephalin (MENK, LENK) have very small picogram concentrations in these pain patients, but no definite conclusion can be reached on their role in trigeminal pain, alone or with monoamines, because of the small numbers, both sample size and concentrations. Interpretive obstacles to such human neurochemical studies suggest that future work might move to human clinical trials comodulating SP down, inhibitory peptides (SOM, CCK) up, and enhancing monoamine systems.

Biogenic Monoamines

Hormonal modulation of HER-2/neu protooncogene messenger ribonucleic acid and p185 protein expression in human breast cancer cell lines.

Recent work has suggested that overexpression of the HER-2/neu protooncogene may play a role in the aggressive clinical behavior of some breast tumors. Since hormones are also known to change the proliferation rate and invasiveness of these cells, we have studied the effect of sex steroid hormones and antihormones on levels of the HER-2/neu mRNA and protein in human breast cancer cell lines using complementary DNA and antibody probes. In MCF-7 cells, which contain high levels of estrogen receptor and an estradiol (E2)-inducible progesterone receptor (PR), 1 nM E2 caused a rapid drop in HER-2/neu mRNA (4.8 kilobases), to 40% of control values by 6 h, and a more gradual decrease in HER-2/neu protein, to 50% by 24 h. HER-2/neu protein and mRNA levels remained reduced throughout 1 week of E2 treatment. The effect of E2 was dose dependent, with the maximal effect seen with concentrations of 10(-10) M E2 and above, and antiestrogen partly reversed the E2-induced decrease in HER-2/neu expression. These characteristics suggest that the observed modulation of HER-2/neu is an estrogen receptor-mediated process. In contrast, progestins did not change HER-2/neu mRNA or protein levels in E2-primed MCF-7 cells that contain high levels of PR; in T47D cells, which contain low levels of ER and high levels of PR, addition of E2 or the progestin R5020 or the antiprogestin RU38,486 had no significant effect on HER-2/neu mRNA or protein levels over 6 days of treatment. These results indicate that estrogen but not progestin modulates HER-2/neu protooncogene expression in these breast cancer cell lines and suggest that aggressiveness associated with high levels of HER-2/neu mRNA and protein may be uncoupled from estrogen-stimulated proliferation in these cells.

Breast Neoplasms

Postgraduate internship in gynecology and obstetrics for physician assistants: a 4-year experience.

Changes in the Hospital Code (405 Regulations) to limit the number of hours worked by residents have been implemented in New York state and may soon become a nation-wide policy. Although their goal is to guarantee quality of patient care and assure education for residents, the limitation of hours worked has increased manpower shortages, some of which could be resolved by using physician assistants with specialty training. To provide this training, a Postgraduate Internship in Gynecology and Obstetrics for Physician Assistants has been developed at the North Central Bronx Hospital and the Montefiore Medical Center. It is the first program of its kind at the postgraduate level to educate physician assistants specifically for practice in obstetrics and gynecology. The program consists of 3 months of didactic lectures to review and update knowledge on topics in medicine, surgery, gynecology, preoperative and postoperative care, cardiac and trauma life support, and critical care, followed by a clinical year similar to that of a rotating physician intern. We believe that such postgraduate educational opportunities in gynecology and obstetrics benefit both the individual physician assistant's growth and development and the level of care delivered, and may be an answer to staffing needs.

Curriculum

Detection of anti-HTLV-I Tax antibodies in HTLV-I enzyme-linked immunosorbent assay-negative individuals.

The HTLV-I tax gene protein (Tax) is not packaged within the mature viral particle from which the proteins for the commercially available enzyme-linked immunosorbent assay (ELISA) are derived. Screening of 162 individuals within a cohort of white intravenous (IV) drug abusers, previously identified as having an increased incidence of HTLV-I infection, demonstrated that seven of them had antibodies to the HTLV-I Tax protein but tested negative in HTLV-I ELISAs and Western blots prepared from purified virion proteins. Three out of 35 individuals in other behaviorally defined high-risk groups also displayed this limited pattern of reactivity to HTLV-I proteins. The presence of the anti-HTLV-I p40/Tax antibodies was determined by radioimmunoprecipitation assay (RIPA), which also revealed low levels of anti-env reactivity. The specificity of the anti-p40 reactivity was confirmed on specific Tax ELISAs and Western blots prepared from recombinantly produced Tax. In vitro gene amplification by the polymerase chain reaction (PCR) was used to establish the presence of sequences homologous to HTLV-I proviral DNA in four/four of these HTLV-I ELISA negative, Tax ELISA/Tax western blot/RIPA positive individuals. These data suggest that the true incidence of HTLV-I infection within high-risk cohorts is greater than previously reported.

Animals

A high-resolution, fluorescence-based, semiautomated method for DNA fingerprinting.

We describe a fluorescence-based method for the automated analysis of DNA fragments on polyacrylamide gels. A single-stranded oligonucleotide primer (18-mer) with a fluorochrome covalently bound to its 5'-end is annealed to a synthetic oligonucleotide to create a double-stranded oligonucleotide linker with a 5'-overhang complementary to a restriction enzyme site. Cosmid or plasmid DNA is digested with the appropriate restriction enzyme and then ligated to the fluorochrome-labeled linker. The labeled restriction fragments are loaded on a denaturing polyacrylamide gel in a commercially available DNA sequencer. As the restriction fragments migrate through the gel, they intersect a laser beam which excites the fluorochrome-labeled fragment. Fluorescence emission data are captured on a computer in real time and analyzed after the completion of electrophoresis. Fragment length is nearly linearly related to migration time. This method offers very near single-base resolution up to 400 bases and the ability to quantitate fragment size up to 2000 bases. The fluorochrome-labeling chemistry relies on straightforward enzymatic reactions and can be performed in a single reaction tube. Because four different fluorochromes can be used, each of 16 lanes on the gel can be used to analyze four different digest reactions, one in each color. One of the fluorochromes can be used to label size standards in each lane, eliminating interlane variability and allowing more precise estimates of fragment size. We apply the method to the analysis of overlapping cosmids.

Animals

Attitudes of men toward contraception.

This report describes a pilot study conducted to determine the attitudes of men toward contraception. A questionnaire elicited responses from 436 males regarding: Personal data; contraceptive responsibility; contraceptive knowledge; use of contraception and preference for future methods. Results include attitudes toward contraceptive responsibility, assistance to pregnant partners and knowledge regarding eight common contraceptives. Usage of contraceptives in general and condoms and withdrawal specifically is reported. Preference for eight common contraceptive methods is also presented, along with data on delay of intercourse due to lack of contraceptives, partners' requests for male use of condoms/withdrawal and attitudes toward dissemination of contraceptive material to the public. Also reported are attitudes toward development of new contraceptives, use of male sterility shots or pills and the prices that men would pay for newly developed male contraceptives. The most preferred male contraceptive for future development is reported. It was concluded that the survey form and methodology were valid; that men desired to participate in family regulation; that the majority of men placed a low economic value on male contraceptives and finally that the overwhelming majority of men wanted contraceptive information to be widely disseminated in the public.

Abortion, Induced

Diagnostic decision making.

Diagnostic or screening tests are used to help determine whether or not a patient has a certain condition or disease. The ability of a diagnostic test to correctly classify subjects is expressed by the four test characteristics-sensitivity, specificity, predictive value positive, and predictive value negative. This paper describes these characteristics and discusses methods for choosing optimal tests or cutoff points to maximize expected value considering the consequences of incorrect diagnoses. Data drawn from ongoing studies of facial pain are used to illustrate some of these concepts.

Chronic Disease