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Biomedical subjects

J Herrmann

Publications and source records attributed to J Herrmann.

At least 91 records · Page 5Linked to original sources

Soluble lactose-binding lectin from rat intestine with two different carbohydrate-binding domains in the same peptide chain.

Of the multiple soluble lactose-binding (S-Lac) lectins in rat intestine, the major one, tentatively designated RI-H, was previously isolated as a polypeptide of molecular weight approximately 17,000. We here report the sequence of RI-H, as determined both at the peptide level and at the nucleotide level. Surprisingly the cDNA encodes a protein of molecular weight approximately 36,000, and this protein contains two homologous but distinct domains each with sequence elements that are conserved among all S-Lac lectins. The C-terminal domain, designated domain II, corresponds to the lectin with M(r) of 17,000 previously isolated from intestinal extracts and shown to have lactose binding activity. By preparing recombinant protein containing only the N-terminal domain, designated domain I, we here directly demonstrate that it too binds lactose and a related range of sugars that are roughly similar to domain II, but clearly distinct. The new lectin, which we designate L-36, is highly expressed in full-length form in rat small and large intestine and stomach but was not detected in eight other tissues including lung, liver, kidney, and spleen. Each domain has approximately 35% sequence identity with the other domain and with the carbohydrate-binding domain of L-29, another S-Lac lectin, but only about 15% identity with other known S-Lac lectins.

Amino Acid Sequence↗

The Intergroup Rhabdomyosarcoma Study-II.

BACKGROUND: Intergroup Rhabdomyosarcoma Study (IRS)-II, (1978-1984) had the general goals of improving the survival and treatment of children with rhabdomyosarcoma (RMS). METHODS: Nine hundred ninety-nine previously untreated eligible patients entered the study after surgery and were randomized or assigned to therapy by IRS Clinical Group (I-IV), tumor site, and histologic type. Outcomes were compared between treatments and with results of IRS-I (1972-1978). RESULTS: Patients in Group I, excluding extremity alveolar (EA) RMS, were randomized to standard vincristine (V), dactinomycin (A), and cyclophosphamide (C) or standard VA. At 5 years, disease-free survival (DFS) and survival (S) rates were similar between VAC and VA (DFS: 80%, 70%, P = 0.47; S: 85%, 84%, P = 0.73). Patients in Group II, excluding EA RMS, received radiation and were randomized to intensive VA or repetitive-pulse VAC. Outcomes were similar for rates of DFS (69%, 74%, P = 0.83) and S (88%, 79%, P = 0.17). Patients in Group III, excluding certain pelvic tumors, received radiation and were randomized to repetitive-pulse VAC or repetitive-pulse VAdrC-VAC (Adr, Adriamycin [doxorubicin]). Complete remission (CR) rates were close at 74%, 78%, respectively (P = 0.32), as were percentages in CR (73%) and S (66%) rates; the latter outcomes were significantly better than IRS-I (CR: 56%, P < 0.001; S: 50%, P < 0.001). Central nervous system prophylaxis for Group III patients with cranial parameningeal sarcoma increased S rate to 67% from 45% in IRS-I (P < 0.001). Patients in Group IV received the same regimens as Group III; the CR rate was 53%, 38% remained in CR and S rate was 27% with and 26% without Adr (P = 0.90). At 5 years, S rate for IRS-II, including EA and all pelvic tumors, was 63%: an 8% increase over IRS-I (P < 0.001). Outcomes by primary site were as good as, or better than, the IRS-I experience. CONCLUSIONS: Combining all Groups and treatments in IRS-II, the major improvement in S rate at 5 years between studies was in nonmetastatic patients (71% for IRS-II versus 63% for IRS-I, P = 0.01).

Adolescent↗

Vascular adjustment and fluid reabsorption in the human forearm during elevation.

Elevation of vascular hydrostatic pressure is known to increase capillary filtration causing, for example orthostatic plasma fluid losses. The present study investigated possible compensatory fluid intravasation in the human forearm during graded elevation, that is during hydrostatic venous collapse. Recordings were made of forearm fluid volume (impedance-plethysmography), forearm blood flow (venous-occlusion-technique), and finger arterial pressure (Finapres). A group of 20 male subjects were seated upright and had their horizontal right forearm passively elevated to 0, 18, 36, and 54 cm above the heart (3rd intercostal space) after equilibration at a reference level 18 cm below the heart. All positions were maintained for 15 min and taken in random order. The vascular volume which drained or refilled within 1.5 min after change of position was found to increase with height. The slow linear volume reduction representing the transcapillary reabsorption rate was found to be almost identical in the three positions above the heart (0.0382, 0.0372, and 0.0398 ml.100 ml-1.min-1). Forearm blood flow reached its highest values at heart level and decreased with height. Calculated total vascular resistance increased with a progressive slope up to about 200% of the value at heart level. As a main finding similar reabsorption rates suggested good maintenance of capillary pressure in positions up to 54 cm above the heart thus contrasting with findings on the calf. The coincidence with increasing total vascular resistance led us to the conclusion that graded venous collapse indicated by grading in venous volume makes for a considerable decrease in pre- to postcapillary resistance ratio with elevation.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

Factors affecting the serum free thyroxine levels in hospitalized chronic geriatric patients.

OBJECTIVE: Determination of whether nonthyroidal factors affect the diagnostic value of free thyroxine estimation in geriatric patients. DESIGN: Survey. PARTICIPANTS: A convenience sample of 381 non-selected, chronic, hospitalized geriatric patients over 60 years of age (I = relatively good health; II = relatively poor health; III = bad health; subgroups "sine therapia," ie, patients receiving no drugs that affect FT4) and 180 20-40 year old healthy persons. MEASUREMENTS: Thyrotropin-releasing hormone test; thyrotropin (TSH); free thyroxine (FT4, measured in part by two parallel methods) estimation in a screening study; and thyroxine-binding globulin and thyroxine-binding-inhibitor activity measurements. RESULTS: The normal FT4 ranges of the euthyroid geriatric (n = 210) and healthy young groups were similar. In the "sine therapia" euthyroid patients, FT4 decreased with age but increase with the severity of illness. High FT4 levels with non-suppressed TSH were more frequent in patients in poor and bad health. (I = 6/112; II = 14/140; III = 13/74; P < 0.01). The serum thyroxine-binding-inhibitor activity of euthyroid geriatric patients correlated with the severity of their clinical state (I = 6.22 +/- 5.65 (13); II = 7.40 +/- 4.33 (23); III = 10.04 +/- 5.50 (16) micrograms merthiolate equivalent/microL; ANOVA with log-transformed values: F(2.51) = 3.50, P < 0.05). The mean FT4 was higher in 36 heparin-treated patients (22.81 +/- 4.67 pmol/L) than in the 193 "sine therapia" patients (19.03 +/- 4.23 pmol/L; -P < 0.001). In a convenience subsample of 240 patients, a weak inverse correlation was found between FT4 and the thyroxine-binding globulin (r = -0.14, P < 0.02). Only 5/11 patients with low free thyroxine had hypothyroidism, while 11/46 patients with elevated free thyroxine had hyperthyroidism. CONCLUSIONS: There is no need to modify the normal free thyroxine range for hospitalized geriatric patients. Clinical condition, drug treatment, and, to a lesser extent, age are factors that significantly affect the diagnostic value of FT4 in hospitalized chronic geriatric patients, decreasing the specificity of the test in diagnosing clinical hyper- and hypothyroidism.

Activities of Daily Living↗

Sequence and specificity of a soluble lactose-binding lectin from Xenopus laevis skin.

A 16-kDa lactose-binding lectin comprises 5% or more of the soluble protein in Xenopus laevis skin. This lectin is mainly localized in the cytoplasm of granular gland cells. In response to stress, the lectin along with a variety of toxic and antibiotic peptides are released onto the skin surface by holocrine secretion. We have purified the lectin, sequenced tryptic peptides using tandem mass spectrometry and Edman degradation, and isolated full-length cDNA using a deduced oligonucleotide. Comparison of the cDNA and peptide sequences revealed expression of at least two isolectins, which differ in sequence at only two or three amino acids. Comparison of cDNA with complementary message by ribonuclease protection confirmed expression in approximately equal abundance of two nearly identical messages. The major soluble lactose-binding lectin expressed in Xenopus muscle is composed of these same isolectins, but at 100-fold lower levels. Similarities and distinctions in sequence and carbohydrate-binding specificity indicate that this lectin is a novel member of a family of soluble lactose-binding lectins expressed in a wide range of vertebrate tissues.

Amino Acid Sequence↗

The translocation t(1;22)(p13;q13) is a nonrandom marker specifically associated with acute megakaryocytic leukemia in young children.

We present the nonrandom occurrence, frequency, and degree of immunophenotype association of the t(1;22)(p13;q13) in children with acute nonlymphocytic leukemia (ANLL). This karyotype anomaly occurred in leukemia cells from five of 445 (1.1%) children with newly diagnosed ANLL who were successfully studied by cytogenetic analysis at four European centers between January 1987 and January 1992. The occurrence of the t(1;22) was restricted to the French-American-British classification (FAB) subtype M7. The overall incidence in children with acute megakaryocytic leukemia (AMKL) was 27.8% (5/18 cases); in infants with AMKL, the frequency of the t(1;22) was 66.7% (4/6 cases). Three of the patients carrying this anomaly had a diploid karyotype, whereas in two cases a hyperdiploid karyotype was found. However, in all five patients, the t(1;22) was the only translocation event present at diagnosis. All patients received aggressive chemotherapy for acute myelogenous leukemia (AML). Two patients died within 15 months of diagnosis without entering remission. One of three patients who entered remission died 7 months after diagnosis, most likely from intramedullar hemorrhage. Only two of the five children with the t(1;22) who received autologous bone marrow transplantation (BMT) are alive and in complete remission (CR) 23 and 40 months after diagnosis, respectively. At the time of diagnosis, the age of the oldest child carrying the t(1;22) was 18 months. The cases with this chromosome anomaly were compared with an age-matched group of five children with AMKL lacking this translocation. The patients with the t(1;22) had a lower median value of the peripheral white blood cell (WBC) count and a higher median hemoglobin level than the patients from the matched group. In the latter cases, normocellular or hypercellular bone marrow (BM) was detected at diagnosis. In contrast, all children with the t(1;22) in our series had a hypocellular BM. Histological BM analyses were available in three of these patients and showed marked fibrosis. Other clinical and laboratory parameters showed no obvious differences between the matched groups. Despite intensive chemotherapy, AMKL in children appears to be associated with a poor prognosis. The clinical courses of the children with AMKL and the t(1;22) presented may be indicative of a beneficial effect of autologous BMT in this subset of patients.

Antineoplastic Combined Chemotherapy Protocols↗

Trisomy 15 with loss of the paternal 15 as a cause of Prader-Willi syndrome due to maternal disomy.

Uniparental disomy has recently been recognized to cause human disorders, including Prader-Willi syndrome (PWS). We describe a particularly instructive case which raises important issues concerning the mechanisms producing uniparental disomy and whose evaluation provides evidence that trisomy may precede uniparental disomy in a fetus. Chorionic villus sampling performed for advanced maternal age revealed trisomy 15 in all direct and cultured cells, though the fetus appeared normal. Chromosome analysis of amniocytes obtained at 15 wk was normal in over 100 cells studied. The child was hypotonic at birth, and high-resolution banding failed to reveal the deletion of 15q11-13, a deletion which is found in 50%-70% of patients with PWS. Over time, typical features of PWS developed. Molecular genetic analysis using probes for chromosome 15 revealed maternal disomy. Maternal nondisjunction with fertilization of a disomic egg by a normal sperm, followed by loss of the paternal 15, is a likely cause of confined placental mosaicism and uniparental disomy in this case of PWS, and advanced maternal age may be a predisposing factor.

Adult↗

Reference intervals for serum thyrotropin: dependence on the population investigated.

In order to elucidate possible differences of reference intervals in various populations, serum basal thyrotropin (TSH) was measured in euthyroid healthy volunteers (N = 170), in thyroid out-patients (N = 215), in geriatric (N = 354) and in seriously ill (N = 32) patients. The results, except in the healthy control subjects, were compared to the TSH responses (delta TSH) in the Thyrotropin Releasing Hormone test. Normal ranges calculated from the basal TSH of the euthyroid groups of different age were similar. There was a significant positive correlation of basal to delta TSH in all groups but the regression equations expressing the qualitative connection of basal and delta TSH were rather different. The basal TSH cut off point predicting a positive TRH-test (i.e. euthyroidism) with more than 95% probability was higher in the geriatric groups (greater than 0.7 mU/l versus greater than 0.4 mU/l in the other groups). In thyroid out-patients and geriatric patients a measurable (greater than 0.1 mU/l) basal TSH indicated measurable delta TSH (thus excluding clinical hyperthyroidism), while in seriously ill patients only a basal TSH greater than 0.2 mU/l was reliably predictive in this respect. Thus, various populations have different reference intervals for TSH. This fact must be considered when the sensitive TSH is used in different populations as the primary screening parameter for thyroid dysfunctions.

Adolescent↗

[A registry of medullary thyroid cancer in West Germany].

A register for medullary thyroid carcinoma (MTC) in FRG has been set up by the "German Medullary Thyroid Carcinoma Study Group" in 1988. The aim is to provide a basis for collaborative work on MTC especially in the hereditary forms (i.e. multiple endocrine neoplasia [MEN] type IIa, IIb). For these hereditary varieties reliable screening tests exist and, if the disease is detected by family screening in an early stage, curative surgery is possible. Until now 408 patients (234 female, 174 male) with MTC have been reported by 17 cooperative centers. The mean age at diagnosis was 45.5 years. 25% (n = 104) are hereditary forms, most of them MEN IIa (n = 86), 13 are MEN IIb and 18 belong to the familial variety without other endocrinopathy. The mean age at diagnosis for MEN IIa was 36.5 years, MEN IIb 26.9 and for the pure familial form 27.5 years. As 33 patients per year have been diagnosed since 1982, nearly 25% of all expected cases of MTC in FRG have been registered.

Adult↗

Aluminum accumulation in a lotic mayfly at low pH--a laboratory study.

The authors experimentally studied the occurrence of aluminum (Al) accumulation in nymphs of the mayfly Heptagenia sulphurea at low pH (4.5). Nymphs were exposed to two Al concentrations (0.2 and 2 mg inorganic Al liter-1), and two exposure times (2 and 4 weeks), the longer time period also including a molting phase. The major part of the Al was deposited on/in the exuviae of the nymphs, as Al determination in nymphs showed a 70% decrease in Al content after molting. When nymphs were exposed for two instar periods, with a molt in between. Al content almost doubled (2.34 mg Al g-1 dry wt) compared with that of a one-instar treatment (1.24 mg Al g-1 dry wt). This indicated that Al also accumulated within the mayfly nymphs. Determination of Al in emerged adults confirmed that most of the metal was deposited externally on the nymphs. No clear indications of Al accumulation were found in this short-term experiment. The implications for food-web accumulation of Al are that internally accumulated Al may be transferred to terrestrial predators by mayflies and other aquatic insects that leave their final exuvium in the water. However, aquatic insects that make their final molt in the terrestrial environment, and thereby bring adsorbed Al out of the water are more likely vectors.

Aluminum↗

Screening of geriatric patients for thyroid dysfunction with thyrotropin-releasing-hormone test, sensitive thyrotropin and free thyroxine estimation.

Hospitalized geriatric patients (N = 354) from an iodine-deficient area were screened with sensitive thyrotropin (TSH), free and total thyroxine (FT4, T4) and total triiodothyronine (T3) to determine the occurrence rate of clinical and subclinical thyroid dysfunction. The diagnostic value of the tests was compared to each other and to that of the thyrotropin-releasing-hormone test (TRH-test) in order to find the optimal first line screening test in geriatric patients. Clinical hyperthyroidism was found in 13, subclinical hyperthyroidism in 10, overt hypothyroidism in 6 and subclinical hypothyroidism in 8 cases. 20.6% of the patients were euthyroid but had subnormal TSH response to TRH, as a sign of possible thyroid autonomy. The low occurrence rate of clinical thyroid disorders (4.8%) does not justify the screening of geriatric patients in general, but the high probability of thyroid autonomy makes reasonable the investigation of every geriatric patient before iodine administration. Suppressed basal TSH and high FT4 were found to be both sensitive and specific in diagnosing clinical hyperthyroidism, but the predictive value was insufficient; elevated T4 and T3 are specific, but not sensitive. Basal TSH is sensitive, specific and has a good predictive value in diagnosing euthyroidism, whereas normal T4, FT4 or T3 are not specific enough for euthyroidism. Basal TSH is better as a first line test of thyroid function than FT4. A normal basal TSH confirms euthyroidism by itself. Other tests (TRH test, T4, FT4, T3) are necessary to elucidate the clinical importance of a subnormal or suppressed basal TSH.

Aged↗

Multimodal therapy for the management of nonpelvic, localized Ewing's sarcoma of bone: intergroup study IESS-II.

Two hundred fourteen eligible patients with previously untreated, localized Ewing's sarcoma of bone were randomized on IESS-II to receive Adriamycin (ADR; doxorubicin; Adria Laboratories, Columbus, OH), cyclophosphamide, vincristine, and dactinomycin by either a high-dose intermittent method (treatment [trt] 1) or a moderate-dose continuous method (trt 2) similar to the four-drug arm of IESS-I. Patient characteristics (sex, primary site, type of surgery) were stratified at the time of registration; these and other patient characteristics (age, time from symptoms to diagnosis, race) were distributed similarly between treatments. Surgical resection was encouraged, but not mandatory. Local radiation therapy was the same as for IESS-I. The median follow-up time is 5.6 years. The overall outcome was significantly better on trt 1 than on trt 2. At 5 years, the estimated percentages of patients who were disease-free, relapse-free, and surviving were 68%, 73%, and 77% for trt 1 and 48%, 56%, and 63% for trt 2 (P = .02, .03, and .05, respectively). The major reason for treatment failure for both treatment groups was the development of metastatic disease. The lung was the most common site of metastases followed by bone sites. The combined incidence of severe or worse toxicity (67%) was comparable between the treatments; however, severe or worse cardiovascular toxicity was significantly greater on trt 1. Tne only treatment-associated deaths (N = 3) were on trt 1 and were cardiac-related.

Adolescent↗

[Clinical aspects of the detection of early arthrosis. Degenerative changes of the menisci of the knee joint].

In a series of 420 persons the knee and hip joints were examined anamnestically and clinically. From this series, 146 persons were selected for further examination of one knee joint by means of magnetic resonance imaging (MRI) on a 1.5 Tesla Magnetom; there was a wide range of indications. Only four MRIs showed no pathological findings in the cruciate ligaments, cartilage surfaces, or menisci. Fifty-one menisci showed grade 3 degenerative changes. In 29 cases (57%), isolated horizontal tears were found, in 1 case (2%) an isolated vertical tear, and in 3 cases (6%) combined horizontal and vertical tears. The correlation of the degenerative changes in the medial meniscus and age was significant (P = 0.01). There was no correlation between the degenerative changes of the medial meniscus and femoral or tibial changes of the cartilage. In this series, there was no significant connection between degenerative changes of the medial meniscus and the previously accepted clinical symptomatology.

Adult↗

Computer-controlled sequencing of peptides by tandem mass spectrometry.

A fully automated computer-controlled system was used to generate series of different linked scans at constant B2E and constant neutral loss in the second field-free region. This system has been shown to be suitable for deriving the amino acid sequence of oligopeptides.

Amino Acid Sequence↗