Mechanism of inhibition of red blood cell glutathione reductase activity by BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea).

A study of the mechanism of inhibition of glutathione reductase activity by BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) demonstrated that the enzyme was protected from inhibition by mercaptoethanol. N-Ethylmaleimide competes with BCNU and also protects the enzyme from inhibition. The inhibited enzyme showed decreased affinity for NADPH. Our data suggest that the inhibition of glutathione reductase is due to an alteration of the redox state. Several other red cell enzymes were inhibited by high concentrations of BCNU; these enzymes were also protected by mercaptoethanol. Among alkylating agents tested, only BCNU inhibited glutathione reductase at therapeutic levels.     

Chronic myelogenous leukemia with a complex translocation

A case of Philadelphia chromosome (Ph¹)-positive chronic myelogenous leukemia (CML) with a complex translocation involving chromosomes #3, #9, and #22 is described. All cells in the bone marrow showed this rearrangement and Q-banding analysis showed the karyotype to be 46, XX, t(3;9;22) (p21;q34;q11). This is the third reported case of a 3/9/22 rearrangement in the Ph¹-positive CML in which the break points and direction of transposition of chromosome segments are identical.     

Postmyocardial infarction angina and coronary spasm

Coronary spasm can cause chest pain, and may even culminate in a myocardial infarction, but it is not often considered a cause of chest pain in the early postinfarction period. Three patients who had chest pain early (1 day to 3 weeks) after myocardial infarction were shown to have coronary spasm with ergonovine maleate provocation. Two patients had spasm in the coronary artery associated with the acute infarction; the third had spasm in a remote vessel. Two required intracoronary nitroglycerin to establish patency in the affected vessel. It is concluded that coronary vasospasm can result in postinfarction angina.     

Natural history of tricuspid valve endocarditis: A two dimensional echocardiographic study

Sixteen patients with tricuspid valve endocarditis were studied to define (1) what clinical or echocardiographic subsets are at risk for complications or need for tricuspid valve surgery, and (2) the long-term two dimensional echocardiographic course of tricuspid vegetations. There were 18 episodes of tricuspid endocarditis in the 16 patients; 12 patients had a history of intravenous drug abuse. Staphytococcus aureus was the most common infecting organism (11 patients). Persistent infection, cardiomegaly or radiography and right-sided heart failure were present in all patients undergoing tricuspid valve surgery and in none of the medically treated patients.

Echocardiographic studies demonstrated tricuspid vegetations in 10 patients by M mode and in all 16 by two dimensional technique. Vegetation size, right ventricular enlargement and abnormal septal motion were not of prognostic significance. Two dimensional echocardiographic measurements of vegetation size correlated with surgical pathologic measurements in the four patients who underwent surgery. Serial two dimensional echocardiographic studies were available in eight patients a mean of 10.6 (range 2 to 19.5) months after the initial study: Vegetations had decreased in size or disappeared in seven patients and were essentially unchanged in one patient.

It is concluded that (1) two dimensional echocardiography increases the detection of tricuspid valve vegetations and accurately estimates their size; (2) persistent Infection, cardlomegaly and right-sided heart failure identify a subgroup of patients with tricuspid endocarditis who may have increased risk; (3) no M mode or two dimensional echocardiographic feature is a predictor of outcome; and (4) tricuspid valve vegetations tend to resolve with time.     

Ectopic production of lipotropin by cancer.

Lipotropin (LPH) has been evaluated as a potential tumor marker using a sensitive beta melanocyte-stimulating hormone (beta MSH) radioimmunoassay. All 79 acetic acid extracts of carcinomas of lung, colon, stomach, esophagus and breast contained LPH in concentrations greater than blood; 61 of 79 extracts contained LPH in larger amounts than control tissues from patients without cancer. In a blind prospective study, plasma LPH was quantified in 107 patients admitted for work-up because of an abnormality on a chest roentgenogram. Thirty-one of 33 patients subsequently diagnosed as having benign lesions had plasma LPH within the 95 per cent confidence limits of normal subjects whereas 28 (36 per cent) of the 74 patients subsequently diagnosed histologically as having primary lung carcinoma had elevated levels. In control studies, 13 of 100 patients with chronic obstructive pulmonary disease had elevated plasma LPH levels; three of the 13 with elevated levels and four with normal levels have been diagnosed, during the two years of follow-up, as having lung carcinoma. In control studies of 23 patients with granulomatous lung disease, 22 had normal levels of LPH. In those with carcinoma of the colon elevated plasma LPH levels were observed in two of 21 untreated patients and in 11 of 61 patients receiving noncurative chemotherapy. Elevated plasma LPH levels were also observed in 10 of 59 patients with breast cancer, eight of 28 with pancreatic cancer, eight of 22 with gastric or esophageal cancer, six of 16 with renal cancer, four of eight with prostatic cancer, one of seven with cervical cancer and one of six with ovarian cancer. We conclude, an elevated LPH level is frequently observed in blood and tumor tissue from patients with various types of carcinoma.     

In vivo reversal of thyroxine induction of DNA synthesis by dibutyrly cyclic AMP in developing rat cerebellum.

Thyroxine, dibutyryl cyclic AMP, and a combination of both drugs were administered daily from birth to 2, 2 and 3 pups, respectively from each of 5 litters of Sprague-Dawley rats. Body weight, brain weight, cerebellar weight, and cerebellar DNA were measured in each animal at age 5 days and compared with values from a pair of controls from each litter. Cerebellar weight and DNA content were affected more severely than body weight in cyclic AMP-treated animals, with cerebellar DNA reduced significantly to 88% of control values. Cerebellar DNA was significantly elevated to 117% of control values in thyroxine-treated animals. This augmentation of cerebellar DNA synthesis by thyroxine was negated by administration of dibutyryl cyclic AMP 10 min prior to the thyroxine injection. These results support an hypothesis that the enhancement of cerebellar cell division by thyroxine involves an increase in the ratio of intracellular cyclic guanosine monophosphate to cyclic adenosine monophosphate. The reversal of the thyroxine-induced increase in cerebellar DNA synthesis by a prior injection of dibutyryl cyclic AMP suggests that the early stimulation of cell division by thyroxine may be mediated by cyclic AMP, and that the intracellular balance between cerebellar cyclic AMP and cyclic GMP was distorted by in vivo elevation of intracellular cyclic AMP levels.     

Lack of interferon induction during hyposensitization therapy in man

Thirteen children 4 to 15 years of age were selected from an allergy clinic as representative of patients who might be expected to demonstrate interferon production in response to commonly employed inhalant allergen injections. Six were studied because of definite or possible untoward reactions with the thought that lymphocyte activation and interferon production might accompany such reactions. All subjects were receiving subcutaneous hyposensitization with aqueous allergen extracts containing multiple allergens at the time the test was done. Nine were receiving maximally tolerated maintenance doses ranging from 188 to 7,500 total protein nitrogen units (PNU) per injection. The remaining four were receiving early increasing extract doses ranging from 0.5 to 94 total PNU per injection. Samples were obtained before injection and at 2, 24, 48, and 168 hours after injection. A positive control consisting of a WHO human interferon standard (40 U. per milliliter) was tested simultaneously. All serum samples were found to be negative. Since the patients were receiving widely varying total extract doses and some experienced significant reactions to the injections, the study suggests that hyposensitization injections employing inhalant allergens in doses commonly used by allergists seldom result in interferon production.     

ProACTH: use for early detection of lung cancer.

ProACTH was identified by radioimmunoassay and column chromatography in extracts of 38 lung carcinomas. One hundred patients were evaluated because of abnormalities on chest roentgenograms; 53 (72 per cent) of 74 with lung cancers had increased plasma ACTH immunoreactivity; all 26 with benign abnormalities had normal ACTH. Of 101 patients with obstructive lung disease, five of 20 with elevated plasma ACTH levels and two of 81 with normal plasma ACTH levels had lung cancer within two years. In three of 31 patients with granulomatous lung disease plasma ACTH levels were elevated during acute exacerbation of the disease, but they returned to normal after recovery. We conclude that plasma ACTH immunoreactivity is frequently increased early in the course of lung carcinoma.