Inoperable rectal cancer.
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Biomedical subjects
Publications and source records attributed to P Miller.
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The concentration of the conjugated bile acid, cholylglycine, in serum is a sensitive and specific indicator of hepatic function. We describe a convenient, specific, and precise radioimmunoassay for cholylglycine, in which 125I-labeled cholylglycyltyrosine is used as tracer. In addition, a blocking agent in the buffer system eliminates binding of bile acids to serum albumin. Therefore no extraction is required. We found no interference by (a) abnormal concentrations of albumin or gamma-globulin, (b) lipemic sera, (c) hemolyzed sera, (d) anticoagulants, or (e) various commonly used drugs. The reference interval for fasting subjects is estimated to be 0.0 to 0.6 mg/L. Our clinical studies show that serum cholylglycine concentrations are usually abnormal in most hepatobiliary diseases, such as viral hepatitis, alcoholic liver disease, cirrhosis, and pediatric liver diseases.
Between April, 1977, and March, 1981, 86 unselected patients with proved squamous cell carcinoma of the esophagus were treated with a combination of chemotherapy and radiotherapy followed by operation whenever feasible. The preoperative chemotherapeutic agents used initially were 5-fluorouracil, and mitomycin C. After December, 1979, cis-platinum was used instead of mitomycin C. Radiotherapy (3,000 rads) of the tumor was begun at the same time as the chemotherapy. An esophagectomy was performed on suitable candidates 3 to 4 weeks after the chemotherapy and radiotherapy were completed. The mucosal lesion disappeared in 69 of the 86 patients, and dysphagia was relieved at least temporarily in 57 of 62 patients. Recurrent dysphagia resulting from fibrosis at the tumor site caused a secondary stenosis in 11 patients. Excellent palliation was obtained in five patients with bronchoesophageal fistulas who had an initial substernal gastric bypass followed by chemotherapy and radiotherapy. Of the 48 patients who had an esophagectomy, 15 (31%) had no tumor in the resected specimen. Eleven of these 15 patients are still alive with no evidence of disease. All patients with a lesion less than 5.0 cm in length had complete regression of the tumor. We believe that this combination of chemotherapy, radiotherapy, and surgical therapy provides excellent palliation, increases resectability, and has a potential for cure.
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A guanosine 3':5'-monophosphate (cGMP)-dependent protein kinase was purified from bovine lung using 8-(6-aminohexylamino)-cAMP-Sepharose. The activity of the purified enzyme was highly dependent on cGMP using histone f2b as a substrate. The self-phosphorylation of the purified enzyme was strongly inhibited by cGMP and not significantly affected by cAMP. A precipitating antiserum prepared in rabbits against the cGMP-dependent protein kinase specifically inhibited the histone kinase activity and the self-phosphorylation of the purified cGMP-dependent protein kinase without affecting the cGMP binding site. This antiserum also specifically inhibited the phosphorylation of the endogenous substrate proteins by endogenous cGMP-dependent protein kinase in smooth muscle membranes, but did not cross-react detectably with catalytic subunit or regulatory subunit of type I or type II cAMP-dependent protein kinase. Conversely, anti-sera against the regulatory subunit of type I or type II cAMP-dependent protein kinase did not cross-react detectably with cGMP-dependent protein kinase. The substantial differences between the immunological properties of the cGMP-dependent and cAMP-dependent protein kinases suggest that these two enzymes have distinct physiological roles.
The F1 hybrid of New Zealand black and New Zealand white mice--the NZB/W mouse--spontaneously develops a disease similar to human systemic lupus erythematosus. Male NZB/W mice with established disease were treated with a stable derivative of prostaglandin E1, 15(S)-15 methyl PGE1 (4 micrograms twice daily) from 7 months of age. The pge analog prolonged survival of these mice: At 14 months 7 of 10 control mice had died, whereas 9 of 10 15(S)-15 methyl PGE1 treated mice remained alive. Thus a dose of 200 micrograms/Kg/day 14(S)-15 methyl PGE1 retards progression of murine lupus.
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A case of encephalopathy complicating cat-scratch disease has been described. Neurologic signs manifested by convulstions and stupor appeared ten days after epitrochlear lymphadenopathy. The clinical course gradually improved over the next few days and recovery was complete. The spinal fluid was normal. The skin test with CSD antigen was positive. In all cases of encephalopathy developing within six weeks following the appearance of unexplained lymphadenopathy, the diagnosis of cat-scratch disease should be entertained. The importance of the cat-scratch disease antigen in diagnosis is emphasized.
We carried out an open study of the effects of large doses (12 to 16 gm per day) of oral choline on medically intractable human complex partial seizures (CPS). Marked increases of plasma choline concentration (75 to 300%) in three subjects were associated with (1) shorter duration of CPS, (2) less postseizure fatigue, and (3) slight increase of seizure frequency. Both the patients and their families considered the patients much improved. No differences in any of these evaluations were noted in a fourth subject who had less of an increase (21%) of plasma choline content. The results suggest that oral choline therapy may be a useful adjunct in the treatment of intractable CPS. A blinded prospective study will be necessary to assess this possibility.
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Knowles pins with incorporated Miller Identification Means have been used on a limited basis by one of the authors. Preliminary experience suggests that numbered pins can lessen the time of operation, the amount of radiation received from X-ray exposure, and the degree of blood loss.
To help delineate how changes in chromatin organization are related to DNA replication and transcription during the HeLa S-3 cell cycle, we have extended previous studies of the composition and structure of chromatin in synchronized G1- and S-HASE CELLS. By analyzing changes in molar ellipticity at 276 nm ([theta 276]) during thermal denaturation, it was found that double-helical DNA molecules in native chromatin have different optical activities and thermal stabilities at these two stages of the cell cycle. Furthermore, profiles of d[theta 276]/dT vs. T indicate that native G1- and S-phase chromatins contain different families of DNA superstructures. To help determine the causes and functional significance of these chromatin reorganizations during the cell cycle, we compared the optical activities and thermal stabilities of DNA in native chromatin with protein-free DNA and DNA in nucleoproteins reconstituted in vitro by NaCl-urea gradient dialysis. In addition, we examined levels of histone phosphorylation, histone acetylation, and types of histone and nonhistone chromosomal proteins (NHCP) found in G1- and S-phase cells and in purified hydroxylapatite, (HAP) fractions of these nuclear proteins which were used for in vitro reconstitution. The results of the present studies indicate that changes in H1-DNA-NHCP interactions occur in vivo, are associated with the phosphorylation of histone 1 molecules, and appear to be responsible for the relaxation of compact G1-phase chromatin superstructures into more open S-phase configurations during the HeLa S-3 cell cycle.
A bioassay, based on tumorigenicity, has been developed to determine the mechanism whereby the blastocyst of the mouse controls malignant expression of embryonal carcinoma. The assay is based upon the incidence of tumors obtained when known numbers of cells of the 402AX strain of embryonal carcinoma are injected into strain 129 mice, compared to the incidence obtained when the same number of embryonal carcinoma cells are incorporated into Swiss-Webster blastocysts that are then injected in strain 129 animals. The results indicate that the blastocyst can regulate one embryonal carcinoma cell consistently; it may have a slight effect on three, but it cannot regulate four or five of them. The position of the embryonal carcinoma cell in the blastocyst is important. Regulation occurs if the embryonal carcinoma cell is placed in the blastocoele cavity, but enhancement of tumorigenicity is obtained if it is placed between the zona pellucida and the trophectoderm. By contrast, the blastocyst is unable to regulate a single B-16 melanoma cell placed in the blastocoele cavity, indicating a degree of specificity for the regulatory process.
Relating the onset of clinical attacks as recorded on a videotape to surface and depth electrographic events improves our ability to define the local or diffuse origin of seizures. In two patients with complex partial seizures, all 14 attacks appeared 3 to 6 seconds after focal discharges began in the amygdala or hippocampus. This meant that the spread of focal electroencephalographic (EEG) paroxysms caused the eventual clinical seizure. In two other patients with 392 generalized seizures and secondary bilateral synchronous paroxysms, a significant number of clinical attacks preceded the first depth or surface electrographic event. This suggested that the attacks originated from brain regions remote from the recording electrodes.
Mothers of anencephalic infants were asked about febrile illness and sauna bathing during their pregnancies. In 7 of 63 affected pregnancies (11%), a history of maternal hyperthermia near the presumed time of anterior neural-groove closure was given. 5 had fever with a maximum recorded temperature ranging from 38.9 to 40.0 degrees C, each case being secondary to a different type of illness. The other 2 had possible hyperthermia episodes as a consequence of sauna bathing, with no infectious agent involved. The frequencies of hyperthermia at the same period of gestation in two control groups were 0% and 0.1%. This excess frequency of maternal hyperthermia at the period of anterior neural-groove closure, and the differing natures of its causes, imply that hyperthermia itself may be an aetiological factor in anencephaly.
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