Tetsuo Nakashima

Primary Myxedema with Thyrotrophin-Binding Inhibitor Immunoglobulins: Clinical and Laboratory Findings in 15 Patients

In a screening of 43 patients with primary myxedema, 9 patients were found to have IgG that inhibits the binding of 125I-thyrotrophin to its receptor (thyrotrophin-binding inhibitor immunoglobulins). Preparations of IgG from these patients did not stimulate thyroidal cyclic adenosine monophosphate generation and blocked thyroid stimulation by thyrotrophin in vitro. Clinical and laboratory features of 15 patients with this inhibitor, including 6 who were previously known, were compared with those of patients without the inhibitor. The patients with inhibitor, 2 men and 13 women, had onset of their hypothyroidism from age 2 to 49 years, and thyroid uptake in these patients was significantly lower than that in patients without inhibitor. Transient hypothyroidism was seen in all 5 infants born to 4 mothers having potent inhibitor immunoglobulins. These clinical findings indicate that thyrotrophin-receptor-blocking antibodies play a pathogenic role in a group of patients with primary myxedema.

Normal bronchial mucus contains high levels of cancer-associated antigens, CA125, CA19-9, and carcinoembryonic antigen

The presence of cancer‐associated antigens CA125, CA19‐9, and carcinoembryonic antigen (CEA) in apparently normal respiratory system was demonstrated histochemically and immunochemically. Epithelial cells lining central airways (trachea, bronchi, and bronchioli) and respiratory glands were specifically stained by antibodies recognizing CA125, CA19‐9, and CEA. Most, if not all, bronchial mucus obtained from patients without pulmonary diseases during general anesthesia contained remarkably high levels of CA125, CA19‐9, and CEA ranging from 190 to 41,000 U/ml (594–4803 U/mg protein), 210 to 95,000 U/ml (294–197,917 U/mg protein), and 6 to 940 ng/ml (14–209 ng/mg protein), respectively, whereas serum antigen levels were normal in all cases examined. These results suggest that CA125, CA19‐9, and CEA are synthesized and secreted by normal epithelial cells of central airways and/or respiratory glands and that these substances are not specific indicators of abnormal cellular activity.

Serum CA 19-9 concentrations and computed tomography findings in patients with pancreatic carcinoma.

Carbohydrate antigen (CA) 19‐9 is a new tumor markerdefined by a monoclonal antibody. Serum CA 19‐9 concentrations and computed tomography (CT) findings were studied in 55 patients with histologically proven adenocarcinomaand in 22 patients with chronic pancreatitis. CA 19‐9 was useful in 83% of cases for the differential diagnosis between pancreatic carcinoma and chronic pancreatitisand serum CA 19‐9 levels in pancreatic carcinoma were highly related to the size of tumors. Serum CA 19‐9 levels greater than 37 U/ml were seen in patients with a tumor of less than 3 cm3 to 5 cmand greater than 5 cm in diameter 13% (1/8)90% (19/21)and 92% (24/26) of casesrespectively. Tumor locationhoweverwas unrelated to serum CA 19‐9 value. These results indicated that the measurement of serum CA 19‐9 concentrations would be useful in mostif not allcases for the differential diagnosis between pancreatic carcinoma and chronic pancreatitisand for the evaluation of tumor burden in patients with pancreatic carcinoma.

Preparation of 67Ga-labeled antibodies using deferoxamine as a bifunctional chelate an improved method

Radionuclides or anti-cancer drugs may be coupled to antibodies for specific transport to target tissues. We have previously reported that several proteins could be rapidly and efficiently labeled with gallium (67Ga) by using deferoxamine (DFO) as a bifunctional chelating agent. In the present paper, we have described the use of hetero-bifunctional agents for the conjugation of DFO with antibodies and investigated the effect of coupling agents on in vitro properties and biodistribution of 67Ga-labeled antibodies. 67Ga-labeled monoclonal antibodies retained antigen-binding activity when prepared under optimum conditions. The use of hetero-bifunctional reagents, such as succinimidyl 6-maleimido-hexanoate (EMCS) or N-succinimidyl-3-(2-pyridyldithio)-propionate (SPDP), which link thioether bonds and disulfide bridges prevented the formation of polymerized antibodies. Although high non-specific uptake in the liver was observed with radiolabels prepared by the homo-bifunctional agent glutaraldehyde, uptake in the liver was low with conjugates linked by hetero-bifunctional agents. 67Ga-labeled antibodies with thioether bonds showed in vivo stability, but the clearance from the circulation was the fastest with the radiolabel holding disulfide bonds. The coupling reagents used to link DFO and antibodies greatly influenced both in vitro properties and in vivo distribution of labeled antibodies and 67Ga-labeled antibodies provide a good model for the study of coupling methods and biodistribution of antibody conjugates.

Application of a self-expanding metallic stent to a strictured esophagojejunostomy

We placed a Gianturco self-expanding metallic stent across the recurrent stricture of an esophagojejunostomy in a patient with gastric cancer. Though excellent passage of food resulted, intractable reflux occurred. Two months later the patient succumbed to recurrent tumor. At autopsy, the stent was patent and was partially covered by esophageal mucosa. There were narrow but deep ulcers around the stent hooks. The Gianturco metallic stent may provide an additional option for treating recurrent enteric strictures after other methods fail. Further refinements of the technique appear necessary.

Construction of An Immunoradiometric Ay for Ovarian Cancer Associated Antigen Ca125 Recognizing Different Antigenic Determinant

We generated five murine monoclonal antibodies reactive with ovarian cancer‐associated antigen CA125. These monoclonal antibodies seemed to bind to separate epitopes from OC125 antibody, known to recognize CA125. A series of im‐munoradiometric assays for measuring serum CA125 values rapidly and sensitively were devised using these monoclonal antibodies. The antigenic determinant of a new immunoradiometric assay was different from that of a currently used CA125 kit employing OC125 both as a catcher and a tracer. However, serum antigen levels were closely correlated to each other and were elevated not only in patients with ovarian cancer, but also in patients with endometriosis and in some normal females during menstruation. These results suggest that CA125 has at least two antigenic determinants close to each other and this new rapid assay is useful, although not specific for ovarian cancer, in patients with gynecological disorders.

Development of new immunoradiometric assay for CA 125 antigen using two monoclonal antibodies produced by immunizing lung cancer cells

CA 125 is an antigen associated with non-mucinous epithelial ovarian cancer, which is defined by OC 125 antibody developed by immunizing ovarian cancer cells. We have produced two monoclonal antibodies, 130-22 and 145-9, by using the human lung adenocarcinoma cell line PC-9. Both 130-22 and 145-9 antibodies recognized CA 125 antigen. However, the binding sites seemed to be separate from those of OC 125. Testing by 9 immunoradiometric assays (IRMA), using different combinations of the 3 monoclonal antibodies 130-22, 145-9 and OC 125 demonstrated that the best standard curve for detecting CA 125 could be obtained by a “simultaneous sandwich” assay based on a mixture of125I-labeled OC 125 and 130-22 or 145-9 coated beads. One-step IRMA, using 130-22 as a tracer and 145-9 as an immunoadsorbent, also showed good reproducibility and sensitivity for measuring CA 125. Antigens were detectable in the culture supernatants of PC-9 cells and 5 of 6 ovarian cancer and endometrial adenocarcinoma cells. These results indicate that one-step IRMA using 130-22 and 145-9 is useful for detecting CA 125 antigen.

Lumbar vertebral bone mineral density in Japanese infants and children: Measurement with dual x-ray absorptiometry

Dual x-ray absorptiometry (DXA) (Hologic QDR-1000/W; Hologic, Inc.) was used to measure lumbar vertebral bone mineral density (BMD) in 83 healthy Japanese infants and children (55 boys and 28 girls) aged 0–17 years, and the values obtained were correlated with age, body weight and body height. The lumbar BMD (average of L1–L4 values) increased with age, with a nearly twofold increase found from preschool age to adolescence. It also increased with body weight and body height. Our results on normal Japanese infants and children appear almost similar to those reported in French and American studies. Because of its great precision and accuracy, low radiation exposure and rapid scanning, DXA may be the most suitable for use in infants and children. With normal Japanese data now available with this technique, pediatricians can better detect metabolic bone diseases in infants and children and follow the bone response to medical intervention in patients with these conditions.

Giant Hydroureteronephrosis Associated with Primary Obstructed Megaureter

The case is presented of a four year old boy with a large left abdominal mass. The patient was diagnosed as having a left giant hydroureteronephrosis due to a primary obstructed megaureter, based on the findings of ultrasonography, micturating cystourethrography, excretion urography, computed tomography and percutaneous antegrade pyeloureterography. Diuretic renography showed that the obstruction was partial. Since a static renal scintigram indicated that renal function on the affected side was moderately well preserved, ureteroplasty is planned.