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The general structure of antagonists of substance P (SP) which was found with the development of Spantide and analogs based on Spantide served for further refinement. The antagonistic potency was tested in vitro on guinea pig ileum and taenia coli. It was unexpectedly found that introduction of Asn6 gave rise to a considerable increase in potency. The exchange of Gln6 for Asn6 entails the shortening of the side chain by one CH2 unit and seems slight for steric advantages and potency increase. The analog [D-Arg1,D-Cl2Phe5,Asn6,D-Trp7,9,Nle11]SP had pA2 values of 7.4 (ileum) and 8.0 (taenia coli). We then used this sequence as a new lead to introduce new changes, which were made in positions 1, 3, 5, 7 and 9. It was found that Arg1 is important, but Lys3 can be exchanged. The Pal3 derivative had pA2 values of 8.1 and 8.0 and the Nle3 counterpart had 7.7 and 7.4 D-Cl2Phe is an effective substituent in position 5. D-Trp in positions 7 and 9 were superior to other alternatives.

Primary testicular neoplasms are not common childhood tumors, comprising about 1% of all childhood malignancies [1]. Embryonal carcinoma is the most common childhood testicular neoplasm. It has been described in a variety of histologic variants as embryonal carcinoma of infancy, orchioblastoma, yolk sac tumor, endodermal sinus tumor, Teilum tumor, and adenocarcinoma with clear cells. Because of the rarity of the tumor, there is no general concensus concerning the management. Recently we encountered two children with embryonal carcinoma of testis who had rather unusual clinical courses. We believe that a report of these cases may contribute to further design of the most suitable therapeutic regimen.

Synthesis and bioassay of about 65 analogs of substance P (SP) over five years yielded the antagonist [D-Arg1,D-Trp7,9,Leu11]-SP, which was named Spantide, and which was used by many investigators as a "tool". Spantide served as a reference antagonist for the design of 47 new peptides toward the goal of more potent inhibitors. Designs emphasized analogs with D-Trp7, D-Trp9, D-Trp10, D-pClPhe10, Nle11, Leu11, Ile11 and Met11, etc. Twenty-one/47 antagonists were superior in potency to that of Spantide, the best was [D-Arg1,D-Na1(5), D-Trp7,9,Nle11]-SP which required a 255-fold increase in SP concentration to give 50% of the maximum response at a concentration of 10(-5)M of the antagonist; this potency is ca. 5 times that of Spantide. For certain, but not all pairs of undecapeptides and truncated analogs, the undecapeptides may be significantly more potent than the truncated counterparts.

Weanling rabbits were fed a purified diet with or without vitamin E supplementation to evaluate the abnormal sequestration of iron in skeletal muscle associated with vitamin E deficiency. A severe myopathy developed in unsupplemented rabbits within 3 to 4 weeks. At this time, the concentration of soluble nonheme iron in biceps femoris muscles had increased from 2.1 +/- 0.4 microgram/g wet weight (mean +/- SD) for six control rabbits to 4.3 +/- 1.4 for 10 vitamin E-deficient rabbits, and total nonheme iron had increased from 5.0 +/- 1.2 to 8.4 +/- 3.3. Soleus muscles had even greater increases in total and soluble nonheme iron concentrations. Intramuscular injection of iron-dextran caused large increases in total and soluble nonheme iron in noninjected muscle of vitamin E-deficient rabbits, which further exaggerated the difference between the two groups. By radioimmunoassay using an antibody to rabbit liver ferritin, the concentration of ferritin in biceps femoris muscles increased from 0.47 +/- 0.18 microgram/g wet weight for seven control rabbits to 6.34 +/- 1.70 for 14 vitamin E-deficient rabbits. Uptake of intravenously injected transferrin-bound iron into muscle of vitamin E-deficient rabbits was not increased in a short term experiment (6 h), but radioiron did accumulate in muscle in a long term experiment (6 days). There was no trapping of heat-damaged erythrocytes, no phagocytosis of intravenously injected carbon particles, and no erythrophagocytosis in muscle. An immunohistological staining method designed to detect ferritin in tissue sections stained muscle from normal rabbits very scantily but intensely stained macrophages in the muscle of vitamin E-deficient rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)

A simpler and more practical sedimentation method for cerebrospinal fluid cytology is described. One-tenth milliliter of cerebrospinal fluid was applied dropwise within the circle of a Reich counting slide, and after sedimentation of the cells to the glass, the fluid was removed. Slides can be stained automatically with a slide stainer. Less cell distortion was observed with the sedimentation method. This method is much simpler and less time-consuming than the original sedimentation method.

A 12-year-old boy was diagnosed as having acute lymphoblastic leukemia (ALL) at the age of 2 years 10 months. Chemotherapy was discontinued after 33 months of continuous remission of ALL. Isolated testicular relapse occurred 5 years after cessation of treatment. Isolated testicular infiltration if it occurs, usually does so within one year after discontinuing treatment. Late bone marrow or extramedullary relapse usually does not occur after four years post therapy. Testicular relapse in this patient occurred five years after completing chemotherapy.

Autoimmune hemolytic anemia (AIHA) is very rarely associated with neoplasia in childhood. However, we have observed AIHA in three children with Hodgkin's disease (HD) in the past 7 years. AIHA presented either prior to, simultaneously with, or years after the diagnosis of HD. Antibodies against erythrocytes were nonspecific. The relationship of AIHA to the activity of underlying HD was quite varied among these three patients. Surgery, radiation therapy, and chemotherapy all may alter the course of AIHA. Coombs' tests may continue to be persistently positive when anemia is absent. Currently, all three patients have no evidence of recurrence of HD, no anemia, negative Coombs' tests 5 years, 22 months, and 14 years 10 months after the initial diagnosis of HD. AIHA should be considered in a child with HD who develops anemia and HD should also be considered in the differential diagnosis in a child with chronic AIHA.

Seven children with acute lymphocytic leukemia developed testicular swelling during bone marrow remission. Needle biopsies and one orchiectomy specimen revealed leukemic infiltration. Another patient encountered concurrent medullary and testicular relapses. The leukemic nature of the testicular infiltration can be readily confirmed on needle biopsies. Orchiectomy should be discouraged. The leukemic infiltration mainly took place in the interstitial spaces. The seminiferous tubules were atrophic and lined by Sertoli cells. Occasional spermatogenic cells could be found in some cases. The leukemic cells were also observed to invade and accumulate beneath the Sertoli cell layer. Destruction of the tubules by the infiltrate was seen in advanced cases. Postradiation biopsies were characterized by fibrosis. The sigeveloped subsequent marrow relapse despite the effective control of the testicular relapse by irradiation. Another important observation is the high incidence of testicular relapse (16.2% so far).

In order to eliminate wasting vials of urokinase, 5000 U/ml aliquots were reconstituted and frozen. The urokinase remained effective for clearing thrombosed catheters for as long as 9 months. When catheters become occluded, patency can be restored by previously frozen urokinase.

A series of compounds based on the semicarbazide structure have been synthesized. Anticonvulsant activity was found in a majority of the compounds using both the maximal electroshock seizure and the subcutaneous pentylenetetrazol seizure threshold tests. Activity of the compounds was weaker than the 1,1,2-trisubstituted semicarbazides previously reported.

Four patients with Fanconi's anemia were evaluated with 99mTc-sulfur colloid bone marrow scans. The scans revealed similar paradoxical and irregular tracer distribution in all four patients. Normal to increased activity was demonstrated in the proximal metaphyses of the humeri with varying degrees of increased activity in more primitive marrow sites in the distal diaphyses of the humeri and tibia, the distal metaphyses of the humeri and femora, and the proximal metaphyses of the ulnae, radii, and tibia. Skip areas of normal distribution were seen in the proximal diaphyses of the humeri and femora. Although the scan reflects only the reticuloendothelial portion of bone marrow, it may be of some value in the differential diagnosis of pancytopenia.