Monoclonal antibody (mAb) A7, produced against human colon cancer, was conjugated with a polymeric prodrug of mitomycin C (MMC), the MMC-dextran conjugate with an anionic charge (MMCDan) and a molecular weight of 70,000. The amino groups were introduced into the MMCDan by reacting ethylenediamine with the carboxyl group in the spacer arm of the dextran bridge by a carbodiimide-catalyzed reaction. The coupling to mAb A7 was performed using SPDP. A 15 M excess of ethylenediamine produced an optimal MMCDan with amino groups, which resulted in a homogenous conjugate (A7-MMCD) with minimal formation of high-molecular-weight aggregates in about a 30% yield of both IgG and MMC. The molar binding ratio of IgG:dextran:MMC in A7-MMCD was estimated to be 1:1.2:40. A7-MMCD, having MMC prodrug properties, released active MMC with a half-life of 29.1 h and had an almost neutral electric charge under physiological conditions. A competitive binding assay using 125I-labeled A7 revealed that the A7-MMCD almost fully retained its antibody-binding activity. The cytotoxicity of A7-MMCD was assayed by determining the degree of inhibition of [3H]-thymidine in corporation in two different ways using the human colon cancer cell line SW1116. A 48-h continuous exposure test revealed that the pharmacological activity of MMC in A7-MMCD was completely preserved. In addition, A7-MMCD exhibited about a 14-fold greater cytotoxicity than MMCDan when the IC50 values determined using a 2-h pretreatment exposure system were compared. These results suggest that A7-MMCD could be useful in immunotargeting chemotherapy for colorectal cancer.

Antibodies, Monoclonal↗

PubMedDate not supplied

Protein nutritional value of a biscuit processed by extrusion cooking: effects on available lysine.

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Animals↗

PubMedDate not supplied

Sliding movement of single actin filaments on one-headed myosin filaments.

The myosin molecule consists of two heads, each of which contains an enzymatic active site and an actin-binding site. The fundamental problem of whether the two heads function independently or cooperatively during muscle contraction has been studied by methods using an actomyosin thread, superprecipitation and chemical modification of muscle fibres. No clear conclusion has yet been reached. We have approached this question using an assay system in which sliding movements of fluorescently labelled single actin filaments along myosin filaments can be observed directly. Here, we report direct measurement of the sliding of single actin filaments along one-headed myosin filaments in which the density of heads was varied over a wide range. Our results show that cooperative interaction between the two heads of myosin is not essential for inducing the sliding movement of actin filaments.

Actins↗

PubMedDate not supplied

Potential use of specific human and chicken antibodies for detection of Hanganutziu-Deicher antigen(s) in sera of cancer patients.

A human Hanganutziu-Deicher (HD) antibody and a chicken anti-N-glycolyneuroaminyllactosylceramide (HD3) antibody were compared in their reaction against HD antigen-active ganglioside (HD3) and a glycoprotein (GP) by radioimmunoassay (RIA). The human antibody had a 50 times higher reactivity with the glycoprotein, while the chicken antibody reacted equally with both antigens. Both antibodies had a higher reactivities with HD antigen(s) in sera of five of eight lung cancer patients than 54 normal human sera. Since four of the above five sera had no abnormal titers to GP, it was concluded that their immunological status was antigen excess. The chicken antibody may be useful in follow-up studies of cancer patients to correlate the expression of HD antigen in tissues and sera with the elevation of HD antibodies, offering alternative methods of clinical prognosis of tumor growth and/or metastases. The human HD antibody may also be useful for the detection of HD antigens of glycoprotein nature.

Animals↗

PubMedDate not supplied

Human lymphoblastoid and fibroblast interferon in the treatment of chronic hepatitis B.

Twenty-six patients, positive for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), hepatitis B virus (HBV)-deoxyribonucleic acid (DNA), and DNA polymerase activity, were treated with human lymphoblastoid interferon (IFN-alpha) or human fibroblast interferon (IFN-beta) after enoxolone glycoside (glycyrrhizinic acid), given for four weeks and then withdrawn. The interferons were given continuously for four weeks. Four months after the treatment, six of 12 patients treated with IFN-alpha were both HBeAg-negative and HBV-DNA-negative while three of 14 patients treated with IFN-beta were HBV-DNA-negative and one was HBeAg-negative. None of the ten untreated control patients became negative for either HBeAg or HBV-DNA. All patients studied remained HBsAg-positive. Both interferons were generally well tolerated. A persistent low-grade fever was reported by more patients in the IFN-beta group and hair and weight loss were more common in the IFN-alpha group. The results indicate that the combination of enoxolone glycoside withdrawal and IFN-alpha treatment reduces HBV replication more effectively than does interferon alone.

Adolescent↗

PubMedDate not supplied

Physiologic response to calcium infusion in newborn and adult dogs.

The physiologic response to intravenous calcium chloride infusion (12 mueq Ca/min/kg for 1.5 h) was measured in 24 newborn dogs, 4-28 days of age, and in 8 adult dogs for comparison. All adult and 18 of the newborn dogs were thyroparathyroidectomized (TPTX). The other 6 newborn dogs were sham operated as controls. Control puppies had higher plasma calcium, lower plasma phosphate and higher renal phosphate excretion than TPTX puppies indicating effective parathormone function in the newborn. Striking differences in response to calcium infusion between TPTX adults and puppies were reflected by a larger rise in serum calcium and in calcium excretion in adults than in intact or TPTX puppies (p less than 0.01). Moreover, plasma phosphate and renal phosphate excretion rose in the adult and fell in the puppy. 4 TPTX adult dogs and 4 TPTX puppies were volume expanded with saline (33 and 42%, respectively). Compared to the adult, the natriuretic response to expansion in the puppy (fractional sodium excretion, FENa, equaled 2.3%) was significantly (p less than 0.05) less than that of the adult (FENa = 8.5%). The calciuretic response, however, was the same for the adult and newborn (FECa = 12.6 and 10.2%, respectively). These results suggest that in response to calcium infusion, there is a greater deposition of calcium and phosphorus in the bone and other tissues of the newborn animal compared to the adult, accounting for the lower rise in serum calcium, the fall in serum phosphate and the lower renal calcium excretion in the puppy. This response is largely independent of parathyroid hormone or calcitonin. The attenuated natriuretic response and good calciuretric response to saline expansion in the newborn dog are consistent with the hypothesis of a linked proximal tubular calcium and sodium reabsorptive mechanism and an unlinked distal nephron mechanism in the newborn animal.

Age Factors↗