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Biomedical subjects

A J Jacobs

Publications and source records attributed to A J Jacobs.

At least 55 records · Page 3Linked to original sources
PubMed1986

In vivo dephosphorylation of WR-2721 monitored by 31P NMR spectroscopy.

The in vivo dephosphorylation of the radioprotective agent S-2-[3-(aminopropylamino)]ethylphosphorothioic acid (WR-2721) in male CD2F1 mice was measured by 31P NMR spectroscopy after i.p. injection. The disappearance of the WR-2721 phosphate NMR signal with time was concurrent with an increase and splitting of the inorganic phosphate NMR signal. The more acidic inorganic phosphate resonance is shown to be attributed to phosphate (inorganic phosphate) in the urine. Using regression first-order kinetic analysis of data, after i.p. injection of 600 mg/kg, the half-life of WR-2721 was determined to be 40.9 +/- 5.9 (S.D.) min (n = 10).

Amifostine↗
PubMed1986

In vivo and in vitro demonstration of reduced myelin synthesis following early postnatal exposure to ionizing radiation in the rat.

Irradiation of the immature central nervous system has been demonstrated histopathologically to result in a reduction in the quantity of myelin seen at later developmental ages [S. A. Gilmore, J. Neuropathol. Exp. Neurol. 22, 294-301 (1963). J. A. Beal and J. L. Hall, J. Neuropathol. Exp. Neurol. 33, 128-143 (1974)]. The results from our investigation indicate that this reduction in myelin content can be attributed to a decrease in sulfatide synthesis. Rats received whole-brain irradiation with 0, 500, 1500, 2000, or 2500 rad at 4 days postnatal (dpn). All of the rats exposed to 2000 or 2500 rad and 70% of those exposed to 1500 rad died within 6 to 10 days. At 17 dpn, animals received single intraperitoneal injections of [35S]sodium sulfate. Myelin synthesis, as indexed by the incorporation of sulfate into total lipids and glycolipids, was reduced in a dose-related fashion. To demonstrate a direct effect of ionizing radiation on myelinogenesis, brain cell reaggregate cultures derived from fetal rats were exposed at 12 days in vitro (div) to 0, 250, 500, 1000, or 1500 rad. A dose-related reduction in [35S]sulfate incorporation through 21 div was demonstrated. Reaggregates exposed to 250 or 500 rad but not 1000 or 1500 rad resumed normal myelin synthesis by 28 div. These changes occurred in the absence of histopathological changes, changes in protein content, and changes in the rate of protein synthesis.

Animals↗
PubMed1985

Complications in patients receiving both irradiation and radical hysterectomy for carcinoma of the uterine cervix.

One hundred and two patients with invasive carcinoma of the uterine cervix, stages IB, IIA, and selected IA and IIB, were treated using combined radiation therapy and radical hysterectomy. Of these, 88 received approximately 2000 rad of pelvic external radiation and a single 5000-6000 mgh intracavitary implant. Major complications were observed in 5 patients. These resolved spontaneously in 1, and were surgically managed in satisfactory manner in the other 4. Only two of the complications occurred in patients receiving low dose preoperative irradiation. The likelihood of complications was closely related to the radiation dosage. Preoperative radiation prior to radical hysterectomy can be given safely provided that dosimetric principles are observed, and that the radiation and surgical techniques are integrated closely.

Adenocarcinoma↗
PubMed1985

Behavioral toxicity and efficacy of WR-2721 as a radioprotectant.

S-2-(3-Aminopropylamino)ethylphosphorothioic acid (WR-2721) is a promising protectant for radiation-induced lethality. However, treatment with WR-2721 also produces nausea, vomiting, diarrhea, and hypotension, which implies severe functional consequences. Three studies were conducted to assess the effects of WR-2721 on rat motor performance and weight and to assess the ability of WR-2721 to mitigate the early performance decrement (PD) produced by ionizing radiation. In the first study, rats trained on the accelerod motor performance task were give 200, 300, or 400 mg/kg WR-2721 intraperitoneally (ip). The highest dose used referenced the maximum tolerated dose in the rat, which is two-thirds the median lethal dose (590 mg/kg). The subjects were tested immediately after treatment, at 30-min intervals for 3 h, and again at 24 h. All groups (N = 6/group) demonstrated a significant decrease in accelerod performance compared to control levels across the eight test trials, which ranged from 24 to 44% in the 200 and 400 mg/kg dose groups, respectively. Performance returned to baseline levels at 24 h. Some deaths occurred at all dose levels. In the second study, motor performance was measured after exposure to radiation alone or a drug/radiation combination (N = 8/group). WR-2721 was administered 30 min before exposure to 130 Gy of gamma radiation from a 60Co source at a dose rate of 20 Gy/min. Rats were tested on the accelerod immediately after WR-2721 treatment and at 10, 15, 30, 60, and 120 min and 24 h following radiation. Performance was significantly depressed compared to control throughout the 24 h following radiation exposure, with and without WR-2721. The decrement produced by WR-2721 and radiation alone appeared to add up to the combined drug/radiation decrement found over the 15- to 120-min test periods. In the third study assessing the effects of WR-2721 on weight, untrained rats treated with 200 or 400 mg/kg WR-2721 exhibited significant weight loss that lasted up to 3 days. Weight returned to pretreatment levels in 15 days, and no deaths occurred. In summary, the data suggest that in the rat (1) WR-2721 is behaviorally toxic at doses relevant to radioprotection, (2) WR-2721 treatment along with the stress of motor performance may combine to lower the level at which lethalities occur, (3) WR-2721 does not protect for radiation-induced PD, and (4) WR-2721 combined with radiation disrupts performance more severely than either radiation or WR-2721 alone.

Amifostine↗
PubMed1984

Chemical induction of ovarian epithelial carcinoma in mice.

Murine ovaries were treated with silk sutures saturated with a solution of 7,12-dimethylbenz(a)anthracene in beeswax. One of 35 animals developed an epithelial carcinoma. This tumor was not successfully transplanted into young animals.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1984

Inhibition of mouse bladder tumor proliferation by murine interferon-gamma and its synergism with interferon-beta.

We studied the effect of interferon-gamma (IFN-gamma) and mouse L-cell interferon (IFN-beta) on the proliferation of a mouse bladder tumor, MBT-2. A liquid culture clonogenic assay was used, and a linear relationship was obtained between the number of cells plated and the number of colonies formed. When the cells were assayed in the presence of various doses of murine IFN-gamma or IFN-beta, colony formation was inhibited in a dose-dependent manner. Partially purified IFN-gamma was more effective than IFN-beta in inhibiting MBT-2 colony formation in that IFN-beta exhibited a 50% inhibition dose of approximately 1000 units/ml, while the 50% inhibition dose for the partially purified IFN-gamma was approximately 70 units/ml. The 50% inhibition dose for recombinant IFN-gamma was 700 units/ml, suggesting that multiple lymphokines were active in the partially purified preparation. Further studies with partially purified IFN-gamma showed that the inhibitory effect was time dependent with the maximal effect observed after 48 hr of exposure in a 5-day assay. Treatment of partially purified IFN-gamma for 24 hr at pH 2.0 resulted in the abrogation of the antiproliferative effect. Studies in which partially purified IFN-gamma preparations were treated with a monoclonal antibody against IFN-gamma also resulted in abrogation of antiproliferative activity, confirming the nature of the antiproliferative agent to be IFN-gamma. Further studies showed that murine recombinant IFN-gamma also inhibited MBT-2 proliferation in a dose-dependent manner, confirming that IFN-gamma alone mediates antiproliferative activity. Combinations of IFN-beta and recombinant IFN-gamma acted synergistically in the inhibition of MBT-2 proliferation.

Animals↗
PubMed1984

Indication for interstitial brachytherapy in carcinoma of the uterine cervix.

More than 40 patients with gynecological, genitourinary, and gastrointestinal malignancies, both primary and recurrent but confined to the pelvis, were treated with interstitial irradiation over a four-year period. Interstitial irradiation was the choice of treatment for early carcinoma of the prostate, carcinoma of the anal canal less than T2, recurrent carcinoma of the uterine cervix, and carcinoma of the cervical stump. The authors' experience in treating recurrent carcinoma of the uterine cervix with interstitial irradiation is the basis for the indications for selecting the technique of interstitial irradiation presented.

Brachytherapy↗
PubMed1983

Surgery following initial treatment of ovarian carcinoma: restaging (second-look) and palliative operations.

Of 73 patients treated for ovarian carcinoma at the University of Nebraska Medical Center between 1976 and 1982, 37 underwent a second operative procedure following initial surgery. A total of 14 had a second look following complete clinical response, 11 had intestinal diversion, and 12 underwent other procedures. Second-look surgery proved useful in evaluating patients in clinical remission and directing subsequent management. The majority of patients whose operations were for persistent or recurrent disease had short survival. However, such surgery helps occasional patients and should be considered when circumstances warrant.

Carcinoma↗
PubMed1983

"C" arm guidance in interstitial brachytherapy of pelvic malignancies.

Since 1979 more than 50 transperineal interstitial implants, both removable and permanent, have been performed at the University of Nebraska Medical Center. The "C" arm of the mobile image-intensifier television unit Siemens Mobile 2 was used to guide the placement of the needles and was found to be useful in achieving accurate implantation.

Brachytherapy↗
PubMed1982

Histologic correlates of virulence in ovarian adenocarcinoma. I. Effect of differentiation.

The original histologic material of 87 patients with Stage III or IV ovarian adenocarcinoma was reviewed. These patients had been treated with cisplatin, alone or in combination. There was a significant association among the morphologic parameters of histologic differentiation, mitotic activity, and cellular pleomorphism. However, none of these was associated either with survival or with maximum response of the tumor among the cisplatin-treated patients. The possible significance of these findings is discussed.

Adenocarcinoma↗
PubMed1982

Diagnostic significance and sequelae of cone biopsy.

All cone biopsies from our institution over a 10-year period were reviewed. Two hundred seventy-one patients underwent 274 procedures. Preoperative colposcopic evaluation markedly reduced the proportion of patients with residual cervical epithelial neoplasia (CIN). No patient in our series required conization for diagnosis of frankly invasive carcinoma. Following colposcopy and conization, 8% of patients had disease extending to the surgical margins; eight of 11 such patients (72%) with adequate follow-up had no further CIN. Colposcopy and cytology underestimate the final pathologic diagnosis in many patients with incomplete visibility of the transformation zone, so conization is mandatory in this circumstance. Conization in pregnancy was associated with increased hemorrhage; colposcopy has reduced the need for this operation in gravid patients.

Biopsy↗
PubMed1982

Treatment of recurrent and persistent germ cell tumors with cisplatin, vinblastine, and bleomycin.

Four patients were treated with vinblastine, cisplatin, and bleomycin for recurrent or persistent germ cell tumors. In all patients a clinical response was achieved. In 2 patients complete response was attained and they are free of disease following second-look laparotomy. One had a mixed germ cell tumor that persisted as dysgerminoma following primary chemotherapy. The other was a true hermaphrodite with pure dysgerminoma. In patients with endodermal sinus tumor transient response was achieved, but the tumors recurred and the patients died within 6 months.

Adolescent↗