PubMed Health⌕ Search

Biomedical subjects

C Gottlieb

Publications and source records attributed to C Gottlieb.

At least 19 recordsLinked to original sources
PubMed1992

5-chlorodeoxycytidine, a radiosensitizer effective against RIF-1 and Lewis lung carcinoma, is also effective against a DMBA-induced mammary adenocarcinoma and the EMT-6 tumor in BALB/c mice.

5-Chlorodeoxycytidine (CldC), coadministered with modulators of pyrimidine metabolism, is an effective radiosensitizer of murine tumors. Past studies that utilized RIF-1 tumors in C3H mice and Lewis lung carcinoma (LLC) in BDF1 mice have been extended with an emphasis on using multiple cycles of drug administration followed by irradiation of LLC and the use of two additional tumor models. Four of seven cures of BDF1 mice bearing LLC were obtained with three doses of 20 Gy irradiation, in which the first and third dose were preceded by a "Standard Protocol" that includes N-(phosphonacetyl)-L-aspartic acid (PALA), 5-fluorodeoxycytidine (FdC), tetrahydrouridine, and the radiosensitizer, 5-chlorodeoxycytidine. No cures were obtained in groups of mice receiving radiation alone or drugs alone, and there were no "no takes" in untreated control groups (six mice/group). Extensive tumor inhibition, exceeding that obtained with drugs or radiation alone, was obtained with two cycles of drugs and radiation combined when a dimethybenzanthracene-induced mammary adenocarcinoma was used in BALB/c mice. With the EMT-6 tumor in BALB/c mice, doses of 10 and 20 Gy were administered 9 and 16 days after tumor implantation, each preceded with the Standard Protocol; this resulted in a tumor growth delay of 24 days. No tumor growth delay occurred with drugs or radiation alone. The omission of PALA, FdC or CldC from the Standard Protocol resulted in loss of tumor control, which was obtained with the complete protocol. The fact that 5-chlorodeoxycytidine is an effective radiosensitizer in four rodent tumor systems is compelling evidence that it has potential as a radiosensitizer of human tumors, especially in view of its tumor selectivity and its resistance to catabolism when used with modulators of its metabolism, and in view of the high levels of the key enzymes in human tumors, which can convert 5-chlorodeoxycytidine to 5-chlorodeoxyuridine triphosphate, the proximate radiosensitizer.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1992

Cytomorphometric analysis of small cell neoplasms of the lung from specimens obtained via bronchoscopy.

Primary neoplasms of the lung composed of small cells consist of undifferentiated small cell carcinoma (UCS), carcinoid tumors (CT) and some non-small cell carcinomas (NonSC) that lack cytoplasmic differentiation. The cytologic identification of tumors from specimens obtained via bronchoscopy sometimes presents difficulties due to overlapping patterns. In order to define additional differentiating criteria, we evaluated Papanicolaou-stained smears from 30 histologically proven cases, 10 from each of the three groups, with statistical analysis of computer-assisted morphologic measures. We identified significant differences between NonSC versus USC and NonSC versus CT with regard to nuclear and cytoplasmic dimensions (P less than .0001) but not between USC and CT. The nuclear:cytoplasmic ratios were similar in all three groups (P = .39). From this preliminary study we conclude that morphometric analysis can distinguish NonSC from USC and CT but not USC from CT.

Biopsy↗
PubMed1991

The effect of 19-hydroxy prostaglandins on the human myometrium in vitro.

Human semen contains high amounts of different prostaglandins of which the quantitatively dominating compounds are 19-hydroxy PGE and 19-hydroxy PGF. The effect of PGE and PGF on the contractility of the human uterus is well known whereas the corresponding 19-hydroxy derivatives have not previously been examined in detail. In the present investigation 19-hydroxy PGE1 was shown to dose-dependently decrease the frequency and the amplitude of the contractions in human myometrial tissue in vitro. The effect of seminal 19-hydroxy prostaglandins may thus be of importance for sperm transport through the female genital tract.

Alprostadil↗
PubMed1991

The fertility potential of male cystic fibrosis patients.

Men suffering from cystic fibrosis (CF) are considered to be infertile because of azoospermia. In testicular biopsies from two patients with CF normal spermatogenesis was found despite the absence of sperm in the ejaculate. Fructose and prostaglandin were not detectable in the semen whereas the levels of acid phosphatase and zinc were within normal limits, indicating normal prostatic function and absence of seminal vesicles. These findings may improve the possibility for male patients with CF to father a child.

Adult↗
PubMed1991

Uterine contractility and interaction between prostaglandins and antiprogestins. Clinical implications.

It is generally believed that progesterone and PGF2 alpha are of major importance in the regulation of uterine contractility. The results summarized herein indicate that progesterone withdrawal is essential for the changes in uterine contractility normally observed during the secretory phase of the menstrual cycle and that the inactivity of the early pregnant uterus is progesterone dependent. Treatment with the antiprogestin RU486 will convert the inactive early pregnant uterus to an active organ and will increase the sensitivity of the myometrium to prostaglandin. These latter effects of antiprogestin have resulted in the development of highly effective, nonsurgical procedures to terminate early pregnancy based on a combined treatment with RU486 and different PG analogues administered orally, vaginally, or intramuscularly. RU486 also has a softening effect on the cervix as demonstrated in late first trimester of pregnancy. This effect may be useful as pretreatment to vacuum aspiration in late first and early second trimester abortion performed by vacuum aspiration or dilatation and curettage. In prostaglandin-induced second trimester abortions, pretreatment with RU486 will significantly reduce the induction-to-abortion interval and the dose of prostaglandin needed.

Abortion, Induced↗
PubMed1991

Mucociliary function following sinus mucosal regeneration.

To evaluate sinus mucosal regeneration and cilia motility after surgical removal, 15 rabbits underwent unilateral removal of maxillary sinus mucosa. The opposite sinus served as an unoperated control. After 10 weeks, specimens were taken for examination from all operated on and control sinuses. Light, dark-field, and electron microscopy were performed. Mucosa from eight of the 15 sinuses operated on showed ciliary regeneration by light microscopy; six of these exhibited motile cilia on dark-field examination. Histopathologic findings of marked fibrosis, decreased seromucinous glands, and significant inflammation were commonly present in the sinuses operated on. Electron microscopy revealed frequent abnormalities, including complex and edematous cilia and fewer than normal cilia per unit area compared to controls. The dark-field, light, and electron microscopic findings of the regenerated, post-surgical mucosa are discussed.

Animals↗
PubMed1991

Vacuum aspiration for termination of early second trimester pregnancy after treatment with vaginal prostaglandin.

Vaginal and intramuscular administration of prostaglandin analogues are routinely used for dilatation of the cervical canal prior to vacuum aspiration in first trimester abortion. Whether the same procedure is also useful during the first weeks of the second trimester has been much less investigated. In the present study, 127 women in the 13th and 14th week of pregnancy were pretreated with 3 mg 9-deoxo-16,16-dimethyl-9-methylene PGE2 administered vaginally 12 hours before surgery. At surgery the cervical canal was dilated to 9.8 mm +/- 2.5 mm (mean +/- SD) and the evacuation of the uterus was uneventful. In 21% of the patients vaginal bleeding occurred prior to the operation. The mean blood loss at surgery was 49 ml and exceeded 100 ml in only 6 patients. Gastrointestinal side effects were rare but analgesic injections were demanded by 29% of the patients during the pretreatment period. No subsequent curettage was performed during the follow-up period but 2 patients (1.6%) were readmitted because of post-abortion endometritis. It can be concluded that after pretreatment with PG, vacuum aspiration can be safely performed during the first weeks of the second trimester.

16,16-Dimethylprostaglandin E2↗
PubMed1991

The use of antiprogestin (RU 486) for termination of second trimester pregnancy.

Pretreatment with laminaria tent is often used in prostaglandin-induced second-trimester abortion to increase efficacy and shorten induction-to-abortion time. In the present study, two alternatives to soften the cervix and dilate the cervical canal, the antiprogestin RU 486 and intra-cervical application of PGE2, were studied. The study included 71 women requesting legal abortion in the 15th to 23rd week of pregnancy who were treated with repeated vaginal applications of 9-methylene PGE2 in a hydrophilic gel (5 mg every 4th hour) following pretreatment with 200 mg of RU 486 and/or intracervical administration of 0.5 mg of PGE2 gel. The mean interval from start of vaginal prostaglandin treatment to abortion was 13.2 h after intracervical PG-treatment, 10.0 h after antiprogestin and 6.6 h after the combined pretreatment. Patients who received pretreatment with RU 486 alone or in combination with intracervical PGE2 experienced the lowest frequency of episodes of vomiting. Of these two pretreatment alternatives, RU 486 alone has the advantage of a shorter hospital stay. It can be concluded that vaginal administration of 9-methylene PGE2 after pretreatment with RU 486 was a highly effective, safe and rapid procedure for termination of mid-trimester pregnancy, was well tolerated by the patients and was associated with few side effects.

16,16-Dimethylprostaglandin E2↗
PubMed1990

Oral administration of RU 486 and 9-methylene PGE2 for termination of early pregnancy.

It has been shown that the antiprogestin RU 486 increases the sensitivity of the early pregnant human uterus to the stimulatory action of prostaglandin E analogues administered vaginally or intramuscularly. To examine if RU 486 also increases uterine sensitivity to a PGE analogue given orally, two investigative approaches were used in the present study: 1) direct registration of uterine contractions before and after administration of 9-methylene PGE2 in untreated and RU-486-treated early pregnant women; and 2) an efficacy trial involving treatment of pregnant women (amenorrhea of 49 days or less) with 25 mg RU 486 twice daily for three or four days followed by 2.5, 5.0 or 10 mg 9-methylene PGE2, or 600 mg RU486 followed by 10 mg 9-methylene PGE2 administered on day 3 and 4. The results showed that oral 9-methylene PGE2 had a clear stimulatory effect on uterine contractility which was further increased by pretreatment with RU 486. Following 2.5, 5.0 or 10.0 mg 9-methylene PGE2, the frequency of complete abortion was the same, or approximately 80%. The success rate is higher than that generally reported for RU 486 treatment alone. If 600 mg RU 486 was complemented with 10 mg 9-methylene PGE2 administered on both days 3 and 4, the frequency of complete abortion increased to 95%. Side effects were of a mild nature and generally occurred following administration of 9-methylene PGE2. The results of the present study indicate that a combined treatment based on oral administration of both the antiprogestin and the prostaglandin analogue can be developed into a highly effective and simple method to terminate early pregnancy.

16,16-Dimethylprostaglandin E2↗
PubMed1990

Diversion colitis: a clinicopathologic study of 21 cases.

Inflammation occurring in a defunctionalized portion of bowel, following either ileostomy or colostomy, has long been recognized by endoscopists. However, little has been written about this entity, particularly the histopathologic changes. Glotzer et al in 1981 described 10 cases, and coined the term "diversion colitis". We studied 21 patients without previous history of inflammatory bowel disease who, for reasons including perforated diverticulitis, carcinoma, or trauma, had loop colostomies or Hartmann's procedure performed. Many of these patients became symptomatic with complaints related to the defunctionalized bowel, including rectal discomfort, pain, discharge, and bleeding. Nineteen patients had endoscopic examinations, which revealed a variety of findings including mucous plugs, friability, petechia, erythema, ulcers, exudate, and nodules or polyps. All except one case had tissue from the excluded portions of bowel available for pathologic examination. Most displayed nonspecific changes with mild-to-moderate lymphoplasmacytic infiltrates in the lamina propria, mild architectural alterations of the crypts, and slight decrease in crypt numbers. Ulceration, cryptitis, and crypt abscesses simulating ulcerative colitis were uncommon findings and were observed almost exclusively in more severe cases. Granulomas were observed in two cases, raising the possibility of Crohn's disease.

Adult↗
PubMed1990

Preclinical evaluation of submillimeter diameter microwave interstitial hyperthermia applicators.

Ultra miniature coaxial cable has been used, with microscopic techniques, to fabricate interstitial hyperthermia applicators having diameters of 0.20 mm, 0.33 mm, and 0.58 mm; commercial applicators have a diameter of 1.1 mm. Animal studies with the 0.33 mm diameter applicators have shown that they produce less local tissue trauma than the larger-diameter devices. All of these applicators operate at 915 MHz and have similar heating patterns because they use the conventional monopole design and the catheters have been approximately scaled to the dimensions of each size applicator. We have measured the heating (SAR) patterns of these applicators in tissue-simulating phantoms, both singly and in arrays, using a miniature electric field probe. As an intermediate step to patient trials, we have examined the ability of these applicators to provide effective heating of perfused tissue, using pig thigh and liver as models. Test results suggest that the durability and power handling capabilities of our submillimeter applicators are adequate for use in patients. These new applicators should be useful in the percutaneous treatment of deep-seated tumors and in intraoperative treatments. The applicators also permit intraluminal or intravascular access to tumors.

Animals↗
PubMed1990

Epitheliosis of the breast. An immunohistochemical characterization and comparison to malignant intraductal proliferations of the breast.

Epitheliosis is a benign intraluminal proliferation in the breast ducts and lobules that needs to be distinguished from ductal carcinoma in situ (DCIS). The histogenesis and differentiation of cells comprising epitheliosis have been the subject of some controversy. We evaluated the expression of a high-molecular-weight keratin (34 beta E12), muscle-specific actin (HHF-35), and S-100 protein immunoreactivity in formalin-fixed sections of the breast with epitheliosis and DCIS. In 28 of 30 cases of epitheliosis, there was strong HMW keratin immunoreactivity in the streaming sheetlike intraluminal proliferations. In contrast, 35 of 40 cases of DCIS (nonpapillary and papillary) were nonreactive for HMW keratin; the other five were weakly reactive. Furthermore, in 10 cases of DCIS, some ducts had isolated or small aggregates of HMW keratin-positive benign cells on the luminal aspects of the neoplastic proliferation that were reminiscent of a pagetoid pattern. Muscle actin-stained sections were analyzed to assess myoepithelial (ME) cell participation in epitheliosis. Muscle actin-positive ME cells were present at the periphery of the involved ducts but were absent or rare within epitheliosis. The distribution of ME cells--i.e., at the periphery of the spaces involved--was similar in DCIS and epitheliosis. S-100 protein was weakly but relatively consistently expressed by epitheliosis, but all cases of DCIS were negative. Six cases of atypical ductal hyperplasia included in the study were negative for HMW keratin, muscle actin, and S-100 protein. The immunohistochemical profile of epitheliosis indicates that it is primarily an epithelial proliferation with strong HMW keratin and weak S-100 protein expression but without ME cell participation. The distinct differences in HMW keratin expression of epitheliosis and intraductal carcinoma appear to reflect a consistent antigenic difference in these two biologically distinct forms of proliferation.

Actins↗
PubMed1990

Expression and localization of gastrin messenger RNA and peptide in spermatogenic cells.

In previous studies we have shown that the gene encoding cholecystokinin (CCK) is expressed in spermatogenic cells of several mammalian species. In the present study we show that a gene homologous to the CCK-related hormone, gastrin, is expressed in the human testis. The mRNA hybridizing to a human gastrin cDNA probe in the human testis was of the same size (0.7 kb) as gastrin mRNA in the human antrum. By in situ hybridization the gastrinlike mRNA was localized to seminiferous tubules. Immunocytochemical staining of human testis revealed gastrinlike peptides in the seminiferous tubules primarily at a position corresponding to spermatids and spermatozoa. In ejaculated spermatozoa gastrinlike immunoreactivity was localized to the acrosome. Acrosomal localization could also be shown in spermatids with electron microscopy. Extracts of the human testis contained significant amounts of progastrin, but no bioactive amidated gastrins. In contrast, ejaculated sperm contained mature carboxyamidated gastrin 34 and gastrin 17. The concentration of gastrin in ejaculated human spermatozoa varied considerably between individuals. We suggest that amidated gastrin (in humans) and CCK (in other mammals) are released during the acrosome reaction and that they may be important for fertilization.

Animals↗
PubMed1990

Myoepithelial cells in the differential diagnosis of complex benign and malignant breast lesions: an immunohistochemical study.

The distinction between sclerosing adenosis, radial scars, noninvasive carcinomas occurring in sclerosing adenosis, and invasive carcinoma can be difficult. The identification of a myoepithelial (ME) cell layer is helpful in establishing a diagnosis of complex benign breast proliferation as well as intraepithelial neoplasia in sclerosing adenosis. We reviewed pathologic material from patients with tubular carcinoma (23) and complex breast proliferations (28), including sclerosing adenosis (12), radial scars (9), sclerosing adenosis with intraepithelial neoplasia (5), and sclerosing adenosis with atypical apocrine metaplasia (2). Immunoperoxidase stains on formalin-fixed, paraffin-embedded tissue using a muscle actin-specific antibody of clone HHF35 and high molecular weight cytokeratin of clone 34 beta E12 (HMW keratin) were performed to identify myoepithelial cells. Muscle actin was uniformly reliable in staining ME cells, as well as other actin-containing cells such as myofibroblasts and vascular smooth muscle. HMW keratin was less reliable, being poorly sensitive and less specific than muscle actin for labeling of ME cells. ME cells were readily identified at the periphery of ductules in all complex benign breast lesions. The presence of ME cells distinguished intraepithelial neoplasia involving sclerosing adenosis from invasive carcinomas. Well differentiated invasive carcinoma forming tubular structures lacked a ME cell layer.

Actins↗
PubMed1989

15-Keto-13,14-dihydroprostaglandin E2- and F2 alpha-metabolite levels in blood from men and women given prostaglandin E2 orally.

Prostaglandin E2 (PGE2) was administered orally in a dose of 1 mg to healthy males (n = 20) and females (n = 10). Blood levels of 15-keto-13,14-dihydroprostaglandin F2 alpha (PGF2 alpha-M) and 15-keto-13,14-dihydroprostaglandin E2 (PGE2-M), determined as the rearrangement product 11-deoxy-15-keto-13,14-dihydro-11 beta, 16-cycloprostaglandin E2 (PGE2-cyclo-M), were measured. The levels of the two PG metabolites increased already 10 minutes after ingestion of the tablet and the mean peak value for PGE2-cyclo-M in the men was 4.64 nmol/l which was reached 50 minutes after PGE2 administration. The mean peak value in women was 4.99 nmol/l which was obtained after 30 minutes. The increase in PGE2-cyclo-M concentration was significantly faster (p less than 0.05) in women than in the men. The mean plasma concentration of PGF2 alpha in males were 0.20 nmol/l prior to treatment and rose after PGE2 ingestion to mean peak level of 0.84 nmol/l after 70 minutes. The corresponding values for the females were 0.18 nmol/l and 0.88 nmol/l 50 minutes into treatment. When the data from both sexes were amalgamated PGE2-cyclo-M peak levels were reached significantly (p = 0.004) sooner than the PGF2 alpha-M peak. The two PG metabolites returned to baseline levels in 70% of the individuals after 240 minutes. The increase in PGF2 alpha-M concentration following oral administration of PGE2 indicates that part of the PGE2 was reduced to PGF2 alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1989

Variation in, and inter-relationship between, prostaglandin levels and other semen parameters in normal men.

In each of 135 ejaculates from 46 healthy men, semen volume, various sperm parameters and the level of prostaglandins (PGs) were determined. Data were analysed to determine the within- and between-subject variability, the effect of abstinence period and the correlation between different parameters. Data which did not reveal a Gaussian distribution were transformed logarithmically. For all variables the between-subject variance exceeded the variation within subjects (P less than 0.001). Variation in time of abstinence between 1 and 3 days influenced semen volume and sperm content as well as the content of 19-hydroxylated PGs, but did not affect sperm motility or the concentration of PGE or PGF. A significant negative correlation was found between the seminal content of PGE and PGF and the total sperm count as well as the sperm concentration. Sperm motility was related to the balance between the content of 19-hydroxy PGE and 19-hydroxy PGF but not to their separate concentrations. The ratio between 19-hydroxy PGE and 19-hydroxy PGF did not change when the time of abstinence differed. Synthesis of the two 19-hydroxylated PGs seemed to be regulated by the same mechanism, but their hydroxylation capacity still varied considerably between individuals.

Humans↗