Conversion of thyroxine to triiodothyronine in normal human subjects.

The conversion of thyroxine to triiodothyronine, previously demonstrated in athyreotic human subjects, has been investigated in normal subjects who were given intravenous injections of purified thyroxine labeled with carbon-14 in ring A and in the alanine side chain. Evidence for the conversion of T4 to T3 was provided by the finding of carbon-14 in the T3 fraction isolated from serums. It is estimated that an appreciable fraction of T4 may be transformed to T3 in normal man.

Determination of triiodothyronine concentration in human serum.

A simplified method has been described for the measurement of triiodothyronine (T3) in human serum. The sensitivity was sufficient for determinations on hypothyroid as well as normal and thyrotoxic sera. The values obtained have been in reasonable agreement with a double isotope derivative assay. The normal T3 concentration in human serum approximates 0.2 mug/100 ml; the mean +/-SD of 31 normal sera was 220 +/-27 ng/100 ml. Elevations were observed in sera from 40 patients with thyrotoxicosis (752 +/-282 ng/100 ml), and diminutions were found in sera from 10 hypothyroid patients (98+/-48 ng/100 ml). In rare instances thyrotoxicosis may be due to elevated serum T3 with normal thyroxine (T4) concentration. The incidence of this condition remains to be determined. In approximately half the cases with low serum T4 after (131)I therapy, the eumetabolic state may be maintained by normal or elevated T3 concentration. From these data and kinetic studies indicating a rapid turnover it may be inferred that T3 rather than T4 may be the more important hormone in health and in disease.

Preparation and properties of thyroxine-binding alpha globulin (TBG).

Thyroxine-binding alpha globulin (TBG) in human serum was isolated from Cohn fractions IV-5,6 and IV-4 by (1) chromatography on carboxymethyl (CM) cellulose, (2) gel filtration on Sephadex G-200, (3) chromatography on diethylaminoethyl-Sephadex, (4) a novel procedure of "double-gel" electrophoresis, and (5) preparative polyacrylamide gel electrophoresis. The protein was homogeneous by analytical disc gel electrophoresis, immunoelectrophoresis, and ultracentrifugal analyses (sedimentation velocity and sedimentation equilibrium), and after addition of thyroxine-(125)I showed a constant specific radioactivity on polyacrylamide electrophoresis. The sedimentation and diffusion coefficients were s(20, w), 3.0 x 10(-13) sec, and D(20, w), 8.05 x 10(-7) cm(2).sec(-1), and the molecular weight obtained by sedimentation equilibrium was 36,500. Gel filtration studies on Sephadex G-200 demonstrated that the protein had the same elution volume as that of native TBG in serum, apparently excluding the possibility of a subunit of the native protein. Chemical composition was ascertained by amino acid and carbohydrate analyses. The maximal thyroxine (T4)-binding capacity measured by reverse flow paper electrophoresis was 15,000 mug per g of protein, representing more than 2100 times that of the starting material, or about 5000 times that of whole serum. Based on the molecular weight obtained, the TBG preparation could bind 0.7 mole T4 per mole of protein, suggesting a single binding site. The association constant for T4 was estimated to be of the order of 10(10) by competitive binding studies employing TBG and T4-binding prealbumin (TBPA).

Preclinical evaluation of an "instant" 99mTc-labeling kit for antibody imaging.

This communication presents information on the quality and stability of a new conjugate of 99mTc to an anticancer antibody fragment and results of animal imaging and distribution studies. Clinical studies have proved that this labeled antibody can image tumors within 2 hours of i.v. injection. It is produced using an "instant kit," merely requiring addition of [99mTc]pertechnetate to a lyophilized vial containing the fragment and a pertechnetate-reducing agent. Within 5 min of addition of pertechnetate to the vial containing the fragment, [99mTc]pertechnetate is reduced and quantitatively bound to an intrinsic high-affinity receptor present in the Fab'. The Fab'-bound 99mTc is completely stable to challenge with diethylenetriaminepentaacetic acid and human serum albumin. Minimal oxidation and release of 99mTc bound to the fragment were observed when the labeled fragment was incubated for 24 h at 37 degrees C. Animal biodistribution studies were consistent with the known metabolic elimination of a radiolabeled Fab' fragment by the kidney. Tumor localization studies in athymic nude mice bearing xenografts of human colonic carcinoma (GW-39) predicted the positive results later demonstrated in clinical studies.

Comparison of tumor targeting in nude mice by murine monoclonal antibodies directed against different human colorectal cancer antigens.

Tumor targeting of five radioiodinated murine monoclonal antibodies (MAbs) directed against human colorectal cancer were studied in nude mice bearing the GW-39 human colonic tumor xenograft. All of the MAbs are of the IgG1 isotype. Two of the MAbs (NP-4 and MN-14) are directed against a Class III carcinoembryonic antigen-specific epitope, but they differ 10-fold in their affinity. The other three MAbs recognize mucins found in colonic cancer. Mu-9 recognizes a peptide determinant similar to that described previously for a polyclonal goat anti-colon-specific antigen p. G9 identifies an organ-specific, tumor-associated carbohydrate epitope. The tumor targeting of these MAbs was compared to that of B72.3, another anti-mucin MAb. The tumor uptake of all the MAbs were similar on days 1, 3, and 7, with an average maximum accretion of between 30 and 40%/g tumor occurring by day 3. This tumor uptake was maintained for 14 days with the anti-mucin MAbs, whereas the percentage of injected dose/g in the tumor for 2 anti-carcinoembryonic antigen MAbs decreased 2-fold by day 14. Although no statistical difference could be found between the percentage of injected dose/g in the tumor for NP-4 and MN-14 (carcinoembryonic antigen MAbs), in a paired-labeled study using 131I-MN-14 and 125I-NP-4, MN-14 uptake in the tumor was consistently 1.3 times higher than that of NP-4 on all days tested. F(ab')2 fragments showed lower tumor uptake (maximum uptake for NP-4 and Mu-9 was 11% on day 1), but the faster clearance resulted in a 4- to 40-fold increase in tumor/blood ratios on day 3 in comparison to the whole IgGs. Fab' fragments had the lowest tumor uptake of the 3 forms of immunoglobulin, with a maximum of only 5%/g 6 h after injection. However, tumor/blood ratios on day 1 for the Fab' fragments were improved 3-fold over that of F(ab')2. All of these MAbs, except Mu-9, identify epitopes that can be detected in plasma, but none of the MAbs complexed appreciably when mixed in vitro with plasma containing antigen at antigen/MAb ratios anticipated to be encountered most frequently in imaging or therapy applications in humans. However, complexation of the MAbs will occur if antigen in the plasma is markedly elevated. These studies suggest that if used clinically, tumor targeting of colorectal cancer with any of these MAb IgG may be similar if these antigens are present at relatively similar concentrations in tumor.(ABSTRACT TRUNCATED AT 400 WORDS)

Primary oral health care in black Americans: an assessment of current status and future needs.

To improve health for all in the United States by the year 2000, dental health needs must be considered a component of total health and primary care. The failure to address dental needs has reached a crisis level, particularly in the black and underserved communities throughout the nation. Data from several nationwide studies have shown that oral disease is greater in black Americans than their white counterparts. More severe periodontal disease patterns, untreated dental decay, and earlier tooth loss were observed. Key minority subgroups received less preventive care.

Foster-family care for the elderly: surrogate family or mini-institution?

The rationale behind adult foster care (AFC) has been that "participation in the life of the family" is superior to institutionalization. The extent to which AFC is familial has been widely debated, ranging from claims that this environment provides a surrogate family, to claims that it is no more than a mini-institution. This paper discusses the extent to which elderly clients are integrated into the family and the method by which such integration was measured in a sample of one hundred adult foster homes in New York State. The four dimensions used to measure familism were Affection, Social Interaction, the performance of Ritual, and the minimization of Social Distance.

Factors in the admission decision: skilled nursing facilities in New York State.

Little is known about the policies, practices, or procedures that affect the selection of applicants for nursing home admission. Results of a study of skilled nursing facilities (SNFs) in the state of New York revealed that fewer than 5% of the respondents viewed their goal as merely keeping patients comfortable; about half of the facilities reported their goal as preventing further decline. More than 70% of the respondents stated that skilled nursing beds were in short supply in the area served by their facility, while 91% of the respondents reported that their geographic area had a backlog of patients in acute care hospitals awaiting placement in SNFs. The authors discuss the study results in terms of the respondents' type of facility--public, proprietary, or voluntary. They also discuss admissions personnel, multidisciplinary teams, information collection, family involvement, and other factors that influence admission (eg, philosophy of care). The authors conclude that further research is needed to help coordinate the medical and social needs of patients and their families with the administrative needs of the facility.

Admission procedures in skilled nursing facilities.

Little is known about the policies, practices, or procedures that affect the placement of applicants for nursing home care. Toseland and Newman report how financial resources and various forms of physical, mental, and behavioral problems affects the chances that older persons will be admitted to or excluded from nursing facilities.

The meaning of cherished personal possessions for the elderly.

An interview survey was conducted with ninety-four elderly persons, sixty-two in community senior service centers and thirty-two in a nursing home, to find out whether aged persons do identify certain possessions as cherished above all others and to see what meaning these possessions had for their later years. It was found that 81 per cent of the sample could quite readily identify a most cherished object. Different kinds of possessions tended to have different meanings and referents in the lives of the subjects. The lack of a cherished possession was associated with lower life satisfaction scores, which suggests that such a lack might be an indicator of poor adjustment to old age.

Classification decisions within psychogeriatric day care.

Classification decisions play a central role in implementation of day care services. A case study is presented which examines classification decisions within an outpatient multilevel psychogeriatric day care program at a state psychiatric center. Staff cited as relevant criteria: social isolation, severity of psychopathology, home emotional climate, activity, ADL and mental status. Issues related to utilization of criteria, such as relevance, consensus, definition and program changes, are discussed.

Affinity in radioimmunoassay of antibody cross-reactive with carcinoembryonic antigen (CEA) and colon carcinoma antigen-III (CCA-III).

Several antisera raised against purified carcinoembryonic antigen (CEA) were evaluated for their content of antibody cross-reactive with colon carcinoma antigen-III (CCA-III). All antisera gave a reaction of partial identity between CEA and CCA-III and demonstrated a high titer in CEA radioimmunoassay (RIA). Between 50 and 70% of the CEA RIA activity was removed, however, by absorption with soluble CCA-III or adsorption onto CCA-III-containing immunoadsorbents. Immunoadsorbent retained antibody gave a line of complete identity between CEA and CCA-III. Purified CCA-III (2 mug) only partially depressed CEA binding by this common site antibody, whereas nanogram quantities of CCA-III inhibited the reaction between specific CCA-III antibody and radioiodinated CCA-III. In addition, low levels of CEA were equally effective in depressing CEA binding by the common site or CEA-specific antibody. The higher affinity in RIA of the common site antibody for CEA over CCA-III suggests that the common determinant expressed on CEA is stereochemically different from that on CCA-III. The results further demonstrate that interference by plasma CCA-III is not a significant factor in the measurement of CEA by RIA.

Community acceptance of the mentally ill in foster family care.

Community acceptance has been described as essential to the successful placement of the mentally ill in the community. The study reported here examined acceptance of mental patients living in family care homes and found that residents were well accepted by neighbors and by others in the community, albeit on a superficial level, and that acceptance could be predicted by variables relating to the residents' social network.

Identification of initiating agents in myoglobin-induced lipid peroxidation.

Reaction of metmyoglobin with peroxides is known to involve the formation, possibly via a porphyrin radical-cation, of a ferryl (iron(IV)-oxo) species and a protein radical; there is a little information available as to which of these species initiates the damage which is observed on incubating membrane fractions with such mixtures. It is shown in this study that the initial protein radical, which is a tyrosine phenoxyl radical centered at position 103 in the protein, does not react rapidly with erythrocyte membranes. However a tyrosine peroxyl radical, formed by addition of oxygen to this species, does react rapidly, and it is concluded that this radical, together with the ferryl species, is an important initiating species in myoglobin-induced lipid peroxidation.