Lars Bjersing

Spatial and temporal pattern of cellular myc oncogene expression in developing human placenta: Implications for embryonic cell proliferation

We have analyzed staged human placentas by Northern, dot blot, and in situ hybridization to human c-myc probes. Placental RNA exhibits a stage-specific appearance of a 2.4 kb transcript of the c-myc gene. The frequency of this transcript varies 20 to 30 fold over the course of placental development, showing a peak at 4-5 weeks after conception, where the myc transcripts comprise about 0.05% by weight of the total placental mRNA. A clear decline in placental c-myc transcription is seen before the end of the first trimester of pregnancy. In situ hybridization to 125I-labeled myc probes demonstrates an unequal spatial distribution of myc transcripts in placental with particularly high expression in the cytotrophoblastic shell of early placenta. Labeling of placental explants with 3H-thymidine, the localization of myc transcripts to cytotrophoblasts, and the temporal pattern of myc expression all support a strong correlation between myc transcript abundance and cytotrophoblast proliferation. We argue for a role for the c-myc gene in the proliferation of normal cells in this tissue.

On the ultrastructure of granulosa lutein cells in porcine corpus luteum. With special reference to endoplasmic reticulum and steroid hormone synthesis.

SummaryIn young corpora lutea the endoplasmic reticulum membranes are sparse. A marked increase of smooth membranes then follows up to the peak of dioestrus. Continuities between smooth and rough endoplasmic reticulum are obvious during the same period. These observations suggest that the agranular membranes develop from the granular ones.During the most intense development of the endoplasmic reticulum the membranes show a tendency to be arranged in whorls. Since these are numerous only during the period of high progesterone secretion, a multitude of whorls constitutes a useful morphologic sign of high functional activity in the porcine granulosa lutein cells.During the first half of the oestrous cycle the increase in endoplasmic reticulum in general also parallels the increase in progesterone secretion. However, this secretion as well as Δ5-3β-hydroxysteroid dehydrogenase activity declines earlier and more rapidly than the endoplasmic reticulum regresses. Steroid hormone synthesis may therefore be lacking although the agranular membranes appear morphologically normal.The mechanisms of induction of the endoplasmic reticulum membranes and enzymes active in steroid synthesis are discussed and it is suggested that luteinizing hormone (LH) may act as a trigger by increasing transport across membranes.

Ovulation and the mechanism of follicle rupture

SummaryOvarian follicles of twenty-three oestrous rabbits from accurately determined times before and after follicle rupture were studied by light microscopy. Epon embedded material was used, in addition to paraffin sections, to obtain more detailed information. Eighteen animals were given an ovulatory dose of human chorionic gonadotrophin (HCG); ovulation occurs fairly regularly 10–12 hr after HCG.At 4 hr after HCG a prominent oedema appeared in the theca interna region and at 10 hr and later there was an obvious oedema in all layers between membrana granulosa and the surface epithelium; the connective tissue cells were apparently disrupted and widely separated. Already at 4 hr the granulosa cells were slightly dissociated and more so at 8 hr and later.Most distinct changes were found in the germinal epithelium prior to ovulation. The surface cells of the preovulatory follicles increased in size, and from 4 hr and onwards they showed an increasing number of dense and large intracytoplasmic bodies. Such intracellular alterations in the germinal epithelium have not been described before. It is suggested that they may be causally related to follicle rupture.

The epidemiology of hepatocellular carcinoma in patients with acute intermittent porphyria

Objective. To describe the epidemiology, pathogenesis and clinical features of hepatocellular carcinoma (HCC) in patients with acute intermittent porphyria (AIP).

On the ultrastructure of follicles and isolated follicular granulosa cells of porcine ovary

SummaryThe endoplasmic reticulum in granulosa cells of primary, secondary, and small tertiary follicles of the porcine ovary is sparse and largely of the granular type.In granulosa cells of large tertiary follicles the endoplasmic reticulum shows distinct signs of proliferation. Some cells even contain whorls of endoplasmic reticulum membranes, essentially of the agranular variety.Direct continuity between endoplasmic reticulum membranes of the granular and agranular type as well as the continuous increase in agranular membranes suggest that these membranes may originate from the granular membranes.Granulosa cells isolated from large tertiary follicles by microdissection and keptin vitro show essentially the same ultrastructure as granulosa cells of intact large tertiary follicles.Some lipid droplets appear to be localized in cavities of the endoplasmic reticulum. It is suggested that the droplets contain precursor material for steroid hormone synthesis.Finally, the development of the agranular endoplasmic reticulum including the appearance of whorls in some granulosa cells of large tertiary follicles indicates that steroid synthesis may occur in such follicular granulosa cells.

Fine structural demonstration of acid phosphatase in rabbit germinal epithelium prior to induced ovulation.

SummaryThe germinal or surface epithelium covering rabbit Graafian follicles contains occasional small, dark, lysosome-like bodies. After an ovulatory dose of human chorionic gonadotropin (HCG) such bodies gradually increase in size and number. At 8 hr after HCG there is a maximal accumulation in the apical follicle cells; then the dense bodies decrease and just prior to ovulation, 9.5 hr after HCG, only few of them remain in the attenuated surface epithelium.Most of the growing membrane-surrounded bodies probably represent lysosomes, since electron microscopy combined with cytochemistry revealed that many of them contain the lysosomal “marker” enzyme, acid phosphatase.The role of sex steroids and prostaglandins regarding lysosomal growth and labilization is discussed.The close temporal relation between disappearance of the apical surface epithelial lysosomes and disintegration of the underlying tunica albuginea gives further support to our working hypothesis that at least part of the “ovulatory enzymes” emanate from the surface epithelium.The technical assistance of Miss Ingalis Fransson, Miss Kerstin Nilsson and Mrs. Ulla-Britt Westman is greatly appreciated.

Breast carcinoma growth rate described by mammographic doubling time and S‐phase fraction. Correlations to clinical and histopathologic factors in a screened population

Background. In a retrospective study, correlations among mammographic doubling times (DT), clinicopathologic prognostic factors, and cytometric predictors were examined.

Further studies of the surface epithelium covering preovulatory rabbit follicles with special reference to lysosomal alterations

SummaryThe fine structure of the surface epithelium over preovulatory rabbit follicles was examined parallel with visualization of acid phosphatase at the electron microscopical level. Small enzyme positive vesicles were pinched off from the Golgi cisternae and similar vesicles fused and got incorporated into larger lysosomes of dense body type. Some lysosomes appeared in direct continuity with tubular enzyme positive structures. Other possible ways of increase of the lysosomal pool are indicated and discussed.As in previous studies a maximal accumulation of lysosomes was found in the apical epithelium at 8 h after an ovulatory dose of human chorionic gonadotrophin (HCG); thereafter a gradual loss of lysosomes ensued. Before the lysosomes disappeared from the surface epithelium they changed in character. They became more electron-lucent and revealed a fine-fibrillar matrix. Dense bodies deep in the cell interior appeared to communicate with each other and with the extracellular space below the surface epithelium. Openings were never seen towards the peritoneal cavity. The loss of lysosomal content from the apical surface epithelium before follicle rupture appeared in many respects similar to the histamine release process in mast cells.The findings support our working hypothesis that the surface epithelium over Graafian follicles is an essential source of proteolytic enzymes and that these may be released extracellularly and actively contribute to the dissolution of the follicular apex before rupture.

Studies on a feminizing ovarian mesenchymoma (granulosa cell tumor). I. Aspiration biopsy cytology, histology, and ultrastructure

A granulosa cell tumor in a 69‐year‐old woman was diagnosed by aspiration biopsy cytology, and different regions were further studied by light and electron microscopy. An almost continuous series of structures, from areas closely imitating normal ovarian follicles and follicular granulosa cells, to minor regions with theca‐like elements was found. The histogenesis, fine structure, and endocrine activity of steroid producing ovarian tumors was discussed, and it was concluded that feminizing or virilizing ovarian mesenchymoma is a suitable collective term for these tumors.

Histochemical demonstration of ? 5-3?- and 17?-hydroxysteroid dehydrogenase activities in porcine ovary

SummaryIn histochemical investigations with the ditetrazolium salt tetranitro blue tetrazolium as final hydrogen acceptor, Δ5-3β-hydroxysteroid dehydrogenase activity was found in theca interna of sexually mature and even prepuberal sows. In the granulosa cells both Δ6-3β-hydroxysteroid and 17β-hydroxysteroid dehydrogenase reactions were negative except in specimens from some sows in puberty or oestrus. The corpora lutea showed a positive Δ5-3β-hydroxysteroid dehydrogenase activity which was somewhat more pronounced during the first week of dioestrus than in other phases of the oestrous cycle.