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We examined keratins 19 and 8 in extracted human hair follicles using monoclonal antibodies Ks19.1 and CAM5.2, respectively. Ks19.1 reactivity was found in the bulge and infundibulum. Ks19.1(+) cells were dense in the bulge of vellus and intermediate hair follicles. The intact bulge of terminal hair could not be extracted, but the presence of Ks19.1(+) cells was confirmed in transverse sections. Infundibular Ks19.1(+) cells exhibited a dense network pattern of staining in terminal hair follicle, but only a few cells were labeled in vellus and intermediate hair follicles. CAM5.2(+) cells, i.e., Merkel cells, were found in the same locations as Ks19.1(+) cells but were less dense. These patterns of distribution and staining density were not influenced by different phases of hair cycle. Sequential staining of Ks19.1 and CAM5.2 in the same hair follicle demonstrated that the same cells could be reactive for both. However, considering the large number of Ks19.1(+) cells and rather small number of CAM5.2 in the same locations, it was assumed that only a subset of Ks19.1(+) cells are Merkel cells. It was postulated that the bulge area of human adult hair follicles houses embryonic pluripotential cells characterized by stem cells and post-stem cells and that the Merkel cells in the bulge area arise from these immature cells and may play a role in the maintenance and stimulation of this group of immature cells.

Extracted human terminal and vellus hair follicles were prepared by EDTA and examined by light and electron microscopes. These samples were morphologically well preserved and enabled us to observe 3-dimensional (3-D) views of the outer surfaces of hair follicles. Interestingly, the bulge areas of terminal and vellus hair follicles showed several morphological variations, such as knob-like swellings and villous projections, independent of hair cycle. Moreover, skirt-like structures were furnished in the small vellus hair follicles independent of hair cycle, but not terminal and large vellus hair follicles. These morphological variations of human hair follicles were confirmed to genuinely represent 3-D views by means of the conventional transverse and vertical sections of the human skin.

Human scalp skins were treated with 20 mM ethylenediaminetetraacetic acid and terminal hair follicles were extracted with the epidermis. Some terminal hair follicles were morphologically preserved well and provided opportunity to examine three-dimensional distribution of CAM5.2 (K8, 52.5 kD) reactive Merkel cells. In anagen terminal hair of the scalp numerous immunoreactive Merkel cells were distributed in the presumptive bulge area. Distinct swelling as in the bulge of human vellus hair was usually absent; however, in rare instances anagen terminal hair demonstrated unilateral prominent swelling with dense aggregation of Merkel cells. In telogen hair the bulge becomes indistinguishable from the regressed end of the club hair follicle but Merkel cells continued to be abundant. We found morphologic variation of the bulge such as formation of knoblike swellings and villous projections. Interestingly, Merkel cells were also located in these structures. Palisading stockade-like nerve endings were observed surrounding the follicular epithelium at the sebaceous gland level. Merkel cells were sparse in this follicular segment. Variable number of Merkel cells were also scattered in the infundibulum of terminal hair in no association with peripheral nerves.

A case of nevus sebaceus with development of a basal cell epithelioma is described. This case of nevus sebaceus was characterized by an association with extensive nevoid growths of melanocytes in the same lesion. The nevoid growths of melanocytes showed features of an unusual "combined nevus", representing a combination of speckled lentiginous nevus with blue nevi. We discuss the relationship between nevus sebaceus and nevoid growths of melanocytes.

A peculiar case of "nevus on nevus" was reported. A 67-year-old man had had a pigmented lesion in the left hypochondrial area since birth. The clinicopathologic findings of the pigmented lesion revealed a combination of speckled lentiginous nevus and patch-type blue nevus. This case of "nevus on nevus" is not described under the term of combined nevus as is current in the literature; it was considered to be a subtype of the type II atypical blue nevus described by Kawamura.

We report a 28-year-old-Japanese male who had a skin tumor derived from variant type xeroderma pigmentosum (XP), combined with factor XI (FXI) deficiency and type IIB von Willebrand's disease (vWd). The patient had abnormal bleeding history on tooth extraction. FXI clotting activity (FXI:C) and antigen (FXI:Ag) were remarkably decreased (< 0.01 U/ml, < 0.02 U/ml, respectively). Factor VIII (FVIII) clotting activity, von Willebrand factor antigen (vWf:Ag), and ristocetin cofactor (RCoF) were 0.43 U/ml, 45%, and 57%, respectively. Ristocetin-induced platelet agglutination (RIPA) revealed hyper-aggregation compared with a normal control. Multimeric composition of vWf in plasma showed a reduction in high molecular weight forms. The family study revealed two other subjects with homozygous hereditary FXI deficiency and vWd, and five subjects with heterozygous FXI deficiency. The relationship between FXI deficiency and vWd is discussed and previously reported cases are reviewed.

Chemical examination of the leaves of Rubus lambertianus Seringe (Rosaceae) has led to the isolation of four new ellagitannins, which were characterized on the basis of chemical and spectroscopic evidence to be dimers [lambertianins A (6) and B (7)], a trimer [lambertianin C (8)] and a tetramer [lambertianin D (10)], all having sanguisorbic acid ester group(s) as linking unit(s) between glucopyranose moieties. Furthermore, HPLC analyses of fifteen Rubus species collected in Japan and Taiwan revealed that the trimer (8) and the tetramer (10), together with sanguiin H-6 (1), occur widely in these species.

A case of trichilemmal carcinoma occurring in a lesion of solar keratosis was reported. A 92-year-old woman had an erythematous plaque on her face that contained a reddish nodule. Histological examination of the nodule revealed typical features of trichilemmal carcinoma accompanied by those of solar keratosis in the marginal zone. The histological features of the erythematous plaque corresponded with those of solar keratosis. However, in situ the carcinoma developed in the epithelium of a hair follicle as well as in the interfollicular epidermis in the lesion of solar keratosis. We considered it likely that bowenoid malignant transformation occurred in both interadnexal and adnexal epithelium because of actinic damage, and a trichilemmal carcinoma arose. The paper also discussed the histogenesis of trichilemmal carcinoma.

Many morphological variations of bulge areas, such as knob-like swellings, were found in extracted human facial vellus hairs. In anagen vellus hair of the face bulge areas including these knobs had a band-like dense aggregation of CAM5.2 (K8, 52.5 kDa) reactive Merkel cells. In telogen hair the bulge became indistinguishable from the clubbed or regressed end of the follicle but Merkel cells continued to be abundant. The epithelial hood at sebaceous gland level showed most commonly a skirt-like structure but variations were also observed; these were bamboo joints, tulip flower, and long apron configurations. Merkel cells were found sparsely in these structures. Palisading stockade-like nerve endings were observed surrounding the follicular epithelium under the skirt and around the bulge areas including the knobs. Merkel cells were sparse in the follicular segment corresponding to the attachment of stockade nerve endings.

We analyzed the relationship between autoantibody and dermatosis in 22 patients with myelodysplastic syndrome (MDS). These MDS patients consisted of five cases with refractory anemia (RA), three RA with ringed sideroblasts (RARS), eight RA with excess of blasts (RAEB), four RAEB in transformation (RAEB-t), and two chronic myelomonocytic leukemia (CMMoL) according to the FAB classification of MDS. The autoantibody was detected in seven patients, of whom four had rheumatoid factor (RF) and three had antinuclear antibody (ANA). Neither RF-positive nor ANA-positive MDS patients had other autoantibodies. Dermatosis was observed in nine cases of these 22 MDS patients. Five of 7 MDS patients (71%) with autoantibody developed dermatosis in their clinical course, as did four of 15 MDS patients (27%) without autoantibody. All four MDS patients with RF had dermatosis such as anaphylactoid purpura, xerotic dermatitis, thrombophlebitis, ephelides, and genital herpes. One of three MDS patients with ANA had pruritus senilis. The four MDS patients without autoantibody had dermatosis such as erythema nodosum, ichthyosis vulgaris, Sweet syndrome, and thrombophlebitis. Three of four MDS patients with RF had normal liver function tests, while three MDS patients with ANA showed liver dysfunction. Our studies presented here suggested that the dermatosis could develop frequently in MDS patients with autoantibody and that RF was closely related to development of dermatosis in MDS patients, although the dermatosis is not specially fixed.

A unique case of extramammary Paget's disease is reported that may have derived from eccrine porocarcinoma. A palm-sized erythematous plaque on the patient's pubis spread to the lower abdominal wall. The center of the lesion contained a reddish tumor. Histologic findings of the erythematous plaque showed features of extra-mammary Paget's disease. Those of the reddish tumor, however, corresponded most closely to eccrine porocarcinoma, though we could not entirely rule out that the changes corresponded to larger nests of less differentiated Paget cells. The two distinct neoplastic areas showed continuity both clinically and histologically; our case differed from epidermotropic eccrine porocarcinoma in several clinicopathologic respects. Our case suggests the possibility that extramammary Paget's disease could arise from preexisting porocarcinoma.

Effects of several cytokines on des-gamma-carboxy prothrombin (PIVKA II) synthesis in human hepatoma cells were investigated to know the process of PIVKA II production during a liver allograft rejection. Human recombinant interleukin-6 (IL-6) significantly stimulated the PIVKA II synthesis without any influence on the cell proliferation. The effect was almost completely neutralized by the specific anti-IL-6 antibody. Neither tumor necrosis factor (TNF), interleukin-1 (IL-1) nor interferon-gamma (IFN-gamma) had such a stimulative effect. IL-6 appears to stimulate PIVKA II production, and would be a candidate of factors that enhance the production of PIVKA II during a liver allograft rejection.

In this article, we report on 4 cases of a dome-shaped nodule on the dorsum of the finger, which had been present since birth and slowly enlarged. On light microscopic examination, these nodules showed similarities to verrucous hemangioma. However, they were characterized by distinct clinical features and proliferation of dermal connective tissue. We consider these tumors to be a variant of verrucous hemangioma and propose to term them digital verrucous fibroangioma.

Background: Dermatologists sometimes have difficulty in making the diagnosis of a melanocytic tumor., Objective: Our purpose was to establish a noninvasive method for the diagnosis of malignant melanoma. We investigated the diagnostic usefulness of magnetic resonance imaging (MRI) in 23 lesions of primary malignant melanoma, metastatic malignant melanoma, and benign pigmented skin tumors., Methods: The morphologic characteristics and the signal intensity of the tumors were analyzed to differentiate malignant and benign pigmented skin tumors by means of the tumor-to-fat contrast ratio of the signal intensity., Results: The morphologic characteristics of the tumors obtained by MRI were not an absolute criterion for diagnosis of malignant melanoma, but the signal intensity of the tumor assessed by the tumor-to-fat contrast ratio on T2-weighted images clearly differentiated between primary malignant melanoma and benign pigmented skin tumors., Conclusion: These findings indicated that MRI is useful for noninvasive diagnosis of malignant melanoma.

Effects of Tumor Necrosis Factor (TNF), Interleukin-1 (IL-1), Interleukin-6 (IL-6) and Interferon-gamma (IFN-gamma) on the expression of Mn-superoxide dismutase (Mn-SOD) protein were investigated in human hepatoma cells, Hu-H1, which revealed resistance to the cytotoxicity of TNF and IL-1. Both TNF and IL-1 enhanced the Mn-SOD production to the level of 30- to 40-fold. IL-6 also increased the enzyme protein to 2- to 3-fold of the basal level without any cell proliferative effect. A specific antibody against IL-6 almost completely inhibited the induction of Mn-SOD. IL-6, as well as TNF and IL-1, appears to play some role in the Mn-SOD protein expression in human hepatoma cells.

Growth of transplanted hepatic tumours (T-9) was enhanced in immune rats under stress, compared with immune rats in an unstressed condition. Compared with unstressed immune rats, killer activity of mononuclear cells infiltrating the tumours against T-9 cells was significantly reduced in stressed immune rats. In contrast, killer activity of splenocytes obtained from stressed immune rats against T-9 cells was elevated compared with that from unstressed immune rats. In addition, natural killer cell activity of mononuclear cells infiltrating the tumours obtained from stressed immune rats was significantly reduced compared with that from unstressed immune rats. Cell populations infiltrating tumour tissues were identified by flow cytometric analysis. The percentage of CD8+ cells in mononuclear cells isolated from tumour tissues of stressed immune rats was reduced compared with that of unstressed immune rats. Furthermore, interleukin-2 responsiveness of splenocytes was suppressed in stressed immune rats, whereas T cell function as reflected by phytohaemagglutinin- or Concanavalin A-reactivity was unaffected by stress. Collectively, it is likely that stress suppressed the generation of cytotoxic cells from the spleen cells of immune rats.

A case of dysplastic nevi associated with malignant melanoma was reported. The case was characterized by unilateral distribution of dysplastic nevi. Multiple dysplastic nevi were observed only dorsally on the patient's left upper quadrant. To the best of our knowledge, the report of this form of dysplastic nevi is the first in Japan. In addition, dysplastic nevus cell nests were present in histologic contiguity with intraepidermal proliferation of melanoma in the radial growth phase. Histological evidence suggested that the melanoma in our case had probably been derived from the context of dysplastic nevus.

Four triterpenoid saponins were isolated from Amaranthus hypochondriacus which are grain crops in the Nepal, Mexico and South America. Their structures were elucidated based on spectral evidence to be: (1) 3-O-alpha-L-rhamnopyranosyl(1----3)-beta-D-glucuronopyranosyl-2 beta,3 beta-dihydroxyolean-12-en-28-oic acid 28-O-beta-D-glucopyranosyl ester. (2) 3-O-alpha-L-rhamnopyranosyl(1----3)-beta-D-glucuronopyranosyl-2 beta,3 beta- dihydroxyolean-12-en-23-al-28-oic acid 28-O-beta-D-glucopyranosyl ester; (3) 3-O-alpha-L-rhamnopyranosyl(1----3)-beta-D-glucuronopyranosyl-2 beta, 3 beta-dihydroxy-30-norolean-12,20(29)-dien-28-oic acid 28-O-beta-D-glucopyranosyl ester. (4) 3-O-alpha-L-rhamnopyranosyl (1----3)-beta-D-glucuronopyranosyl-2 beta, 3 beta-dihydroxy-30-norolean-12, 20(29)-dien-23-al-28-oic acid 28-O-beta-D-glucopyranosyl ester.

We have suggested that pigmented macules on the palms and/or soles occur in response to various systemic diseases. In the present paper, we evaluated the influences of clinical severity and duration of illness in Japanese subjects. In males, cases who suffered from cerebral vascular accident (CVA) for long periods and/or severely tended to have numerous pigmented macules. In females, cases with CVA did not show any similar tendency. As the result of our prior and present studies, we conclude that underlying systemic disease itself can play a pivotal role in the development of pigmented macules on the palms and/or soles of Japanese subjects. We emphasize that such a pigmented macular eruption with characteristic clinical features is an important sign of internal disorders, including malignancy.

We reported a case of type B chronic hepatitis with high titer of IgM anti-HBc continuously, which progressed to liver cirrhosis rapidly. The patient was a 37-years-old man, and was diagnosed as chronic type B hepatitis with severe activity by laparoscopy and liver biopsy. The titer of IgM anti-HBc persisted high level for more than 2 years. Then the second liver biopsy showed the progression to liver cirrhosis within only about 2 years. It is a very rare case to prolong positive IgM anti-HBc for such a long time. Anti-HBc production of PBMC was enhanced remarkably in this case. We considered that HBc antigens released into serum from hepatocytes with severe exacerbations had enhanced the anti-HBc producing activity of B lymphocytes. And the rapid progression in this case would be due to the episodes of severe exacerbations.

A novel experimental nude mouse model, which is useful for investigation of the mechanisms of PIVKA II synthesis, was established by inoculation with PIVKA II-producing human hepatoma cells (huH-1). We have found markedly elevated levels of PIVKA II in the plasma of nude mice transplanted with huH-1 cells and increased PIVKA II content in huH-1 tumor tissues. Whereas we have not found detectable level of PIVKA II neither in the plasma nor in tumor tissues of nude mice transplanted different human hepatoma cells (HLF) which is not producing PIVKA II. Histology of the tumor tissues produced by huH-1 cells revealed a thick trabecular pattern with blood spaces.

From the leaves of Acanthopanax hypoleucus Makino (Araliaceae), five triterpenoidal saponins, having oleanolic acid and hederagenin as sapogenins, were isolated. On the basis of chemical and spectral data, the structures of two new saponins, named hypoleucosides A (1), and B (5) were elucidated as follows: 1; 3-O-beta-D-glucopyranosyl 11 alpha-methoxy-oleanolic acid 28-O-beta-D-glucopyranosyl ester, 5; 3-O-beta-D-glucopyranosyl-(1----2)-alpha-L-arabinopyranosyl-(1---- 4)-beta-D-glucopyranosyl oleanolic acid 28-O-beta-D-glucopyranosyl-(1----6)-beta-D-glucopyranosyl ester.

Three cases of adult T-cell leukemia (ATL) with cutaneous lesions of disseminated papules or nodules were treated with recombinant human interferon-gamma (IFN-gamma) by intravenous administration. Clinical stage of each case was different, i.e., 1) preleukemic state of ATL (pre-ATL), 2) chronic-type ATL, and 3) crisis-type ATL. We evaluated clinical efficacy of IFN-gamma, and performed immunohistochemical analysis of biopsy specimens derived from cutaneous lesions of the patients both before and during treatment. The case of pre-ATL achieved a complete remission of cutaneous lesions for 18 months. The other cases also obtained clinical responses with a shorter duration, but relapsed while they are still on IFN-gamma therapy. The cutaneous lesions reduced in size during the therapy associated with a decrease in the ratio of Leu3a + 3b (CD4)+ cells in all three cases. After the therapy, Leu7 (HNK-1)+ cells increased in all cases, and LeuM5 (CD11)+ cells did in two. These results suggested that IFN-gamma enhanced tumor immunity although its clinical effect was less clear. Only in the cutaneous lesions of pre-ATL case an increased number of LeuM5+ cells, probably monocyte-macrophage series in host defence, were seen before the therapy. And IFN-gamma was useful for this case after all.

We have examined changes in rectal temperature of mice after subcutaneous administrations of d-methamphetamine alone or methamphetamine plus morphine. Methamphetamine 5 mg/kg produced slight hyperthermia, while simultaneous administration of morphine (25-100 mg/kg), which alone produces hypothermia, potentiated markedly the increase in body temperature by methamphetamine. Methamphetamine showed a hyperthermic effect in a dose-dependent manner in the presence of morphine. The hyperthermia due to methamphetamine plus morphine was avoided by pretreatment with 10 mg/kg naloxone. When animals were pretreated with 2.5 mg/kg haloperidol, hyperthermia due to methamphetamine alone was completely abolished, while that due to methamphetamine plus morphine was still observed. These results showed that dopamine may be implicated in methamphetamine hyperthermia and a haloperidol-nonsensitive mechanism may be involved in the methamphetamine-morphine hyperthermia.

We report two cases of pilomatrix carcinoma. Wide surgical excision, radiation, and chemotherapy were required for the first patient. The tumor eventually revealed the characteristics of a carcinoma, both clinically and histopathologically, as it recurred. In the second case, although the tumor exhibited the histology of pilomatricoma in the central part of the lesion, there were numerous outgrowing irregular nests of basaloid tumor cells with cellular atypia and frequent mitoses; these are the characteristic features of the pilomatrix carcinoma in its early stages.

A 26-year-old man with Gardner's syndrome had numerous subcutaneous nodules over almost his entire body. Histologically, one of them revealed an unusual so-called hybrid cyst composed of epidermal type keratinization and inner root sheath type keratinization. The histologic findings and the possibility of cutaneous cysts based on hair matrix differentiation, more specifically partial differentiation toward the inner root sheath, are discussed.

The effect of antiserum to progesterone on follicular rupture during the ovulatory process was studied. Mean number of ova shed following treatment of immature rats sequentially with PMS and hCG was reduced in a dose-dependent manner by simultaneous injection with increasing doses of antiserum to progesterone. When the animal received 1.2 ml of the antiserum, hCG-induced ovulation was blocked completely. To be effective, antiserum treatment had to be within 6 h of hCG treatment; antiserum given 9 h after hCG was ineffective. Progesterone restored' the antiserum blocked ovulation completely or incompletely when administered intravenously within 6 h of treatment with hCG. The first 6 h was shown to be a progesterone-dependent step in the ovulatory process in this experimental system.

The histologic variety and transformation in cutaneous cryptococcosis with acute lymphocytic leukemia before antifungal treatment and after the start of treatment were studied by the light and electron microscopic examinations. The initial cutaneous lesions before treatment revealed gelatinous tissue reactions, and Cryptococcus neoformans (serotype A) were isolated from the skin biopsy specimen and blood. However, later recurrent cutaneous lesions receiving antifungal treatment revealed suppurative granulomatous tissue reactions, and fungal cultures of the skin biopsy specimen changed to negative even though numerous yeasts stained with PAS were observed in skin lesions. Moreover, in the later lesion a few giant cells contained asteroid bodies without central spores. Ultrastructure of the later cutaneous lesions is presented.

Serial injections of a mixture of prostaglandin (PG) E2 and F2 alpha 0, 2, 4, and 6 h after simultaneous injection of human chorionic gonadotrophin (hCG) and indomethacin incompletely restored the ovulation that would have been blocked by indomethacin in immature rats treated with pregnant mare serum gonadotrophin followed by hCG. Serial injections of another mixture of PGE2 and PGF2 alpha 6, 8, 10 and 12 h after simultaneous injection of hCG and indomethacin similarly reversed, in part, the inhibitory effects of indomethacin on hCG-induced ovulation. In contrast, serial injections of the mixtures of PGE2 and PGF2 alpha 0, 2, 4, 6, 8, 10 and 12 h after simultaneous injection of hCG and indomethacin completely restored the indomethacin-blocked ovulation, suggesting that the prostaglandins mediate the action of hCG on ovulation both in the earlier and later stages of the preovulatory process. Six hours after simultaneous injection of hCG and indomethacin serial injections of a mixture of PGE2 and PGF2 alpha reproduced the acute and temporary increase in concentrations of progesterone and testosterone in plasma which would have been abolished by indomethacin. Progesterone given concurrently with hCG and indomethacin partially antagonized the inhibitory action of indomethacin on ovulation. Serial injections of a mixture of PGE2 and PGF2 alpha 6, 8, 10 and 12 h after concurrent administration of progesterone with hCG and indomethacin completely restored the indomethacin-blocked ovulation, suggesting that progesterone can substitute the action of prostaglandins injected serially in the first half of the preovulatory process. It was concluded that the co-operation of progesterone in the earlier stage and of prostaglandins in the later stage of the preovulatory interval is required to mediate the action of hCG on ovulation.

The main molluscicidal activity of the methanol extract of Lysimachia sikokiana is due to several triterpenic saponins called sakuraso-saponins. The most active component was isolated from the aerial parts and elucidated as 3-O-beta-xylopyranosyl-(1----2)-beta-glucopyranosyl-(1----4)- [beta-glucopyranosyl-(1----2)]-alpha-arabinopyranosyl protoprimulagenin A, named lysikoianoside 1, on the basis of 1H- and 13C-nuclear magnetic resonance spectral data and methylation analysis results.

In immature rats primed with pregnant mare serum gonadotrophin, antiserum to progesterone could prevent or reduce ovulation in response to injected human chorionic gonadotrophin (HCG). To be effective, antiserum treatment had to be within 6 h of gonadotrophin treatment; antiserum given 9 h after HCG was ineffective. Progesterone restored the antiserum blocked ovulation completely or incompletely when administered intravenously within 6 h of treatment with HCG. The first 6 h was shown to be a progesterone-dependent step in the ovulatory process in this experimental system.

The effect of dan-shen extract, the root of Salvia miltiorrhiza, on adenylate cyclase was investigated in both rat brain and rat erythrocytes. The EtOAc fraction of the MeOH extract was proved to have significant inhibitory activity. Potent inhibitory principles in the EtOAc fraction were isolated and identified as 4 polyphenolic acids, rosemarinic acid, lithospermic acid, and their methyl ester derivatives.

The effectiveness of commercially available, chemically generated, topical exothermic pads that elevate skin surface temperature from 42 to 43 degrees C was stressed in 22 patients with psoriasis. Control sites were treated with conventional modalities such as Goeckerman's regimen, as well as with occlusion with nonexothermic pads. Skin lesions in 19 patients disappeared after the use of hyperthermia. The average time required for complete regression in the treated areas was 27 days with hyperthermia, compared with 44 days with Goeckerman's regimen. There were no hyperthermic side effects. Seventeen patients whose skin lesions disappeared with the use of both hyperthermia and Goeckerman's regimen were subsequently reexamined. The hyperthermia produced an equal or longer duration of remission than did Goeckerman's regimen.

Immature Wistar rats were treated with pregnant mare's serum gonadotropin and human chorionic gonadotropin to induce ovulation. The non-steroidal anti-inflammatory drugs indomethacin, diclofenac, flurbiprofen, and phenylbutazone inhibited both the ovulation rate and the normal increase in ovarian prostaglandin E during ovulation. Tolmetin, ibuprofen, and aspirin did not have any significant effect. There was a significant correlation between the ovulation rate and the level of ovarian prostaglandin E following treatment with these drugs. When indomethacin was given in graded doses, there was also a correlation between ovulation rate and the dose-dependent inhibition of ovarian prostaglandin E.