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Biomedical subjects

A Giwercman

Publications and source records attributed to A Giwercman.

At least 127 records · Page 7Linked to original sources

Monoclonal antibody 43-9F as a sensitive immunohistochemical marker of carcinoma in situ of human testis.

Invasive germ cell cancer can be prevented if the neoplasia is diagnosed at the stage of carcinoma in situ (CIS). In routine histologic examination CIS may be overlooked, particularly in prepubertal individuals. The detection of this early malignancy may be greatly facilitated by use of immunohistochemical staining. The authors investigated the sensitivity of an immunohistochemical staining procedure with monoclonal antibody 43-9F in detection of CIS. Testicular specimens from 19 adult and two prepubertal individuals with CIS were tested. Positive staining reaction on the surface of malignant germ cells was encountered in all 21 specimens with CIS. The epithelial cells of the excretory ducts between testis and epididymis, including rete testis and canaliculi efferentes, reacted also positively with 43-9F. No staining was observed in nonmalignant testicular cells including Sertoli cells or Leydig cells in any of these samples or in testicular biopsy specimens from 27 adult and 11 prepubertal subjects without evidence of testicular neoplasia. Monoclonal antibody 43-9F was also found to react with cells of all four tested invasive testicular germ cell tumors. Thus, the monoclonal antibody 43-9F is a sensitive immunohistochemical marker of CIS germ cells and may also be of potential value in detection of invasive testicular cancer.

Adult↗

Insulin-like growth factor I (somatomedin C) in goats during normal lactation and in response to somatotropin treatment.

1. Two experiments were performed. In Experiment 1, IGF-I concentrations in serum were followed in four lactating dairy goats during normal lactation and before, during and after 14 days of daily administration of 10 IU recombinant bovine somatotropin, starting 10 weeks post-partum. In Experiment 2, IGF-I was measured in single blood samples obtained from 40 dairy goats in the first part of lactation. 2. Measured IGF-I concentrations ranged from 4.4-9.0 nM. Concentrations varied during the day with coefficients of variation from 8.9 to 18.4% in the four goats in Experiment 1. There were no systematic trends in the diurnal variations (P greater than 0.75). 3. Concentrations of IGF-I remained fairly constant in all goats in Experiment 1 during the lactational period, and were not related to the changes in milk yield (P greater than 0.65). Similarly, no relationship was found in Experiment 2 between level of milk production and IGF-I concentration in serum. 4. Somatotropin treatment stimulated milk yields by 14 +/- 2.9% (P less than 0.05) and IGF-I concentration by 27.9 +/- 6.7% (P less than 0.05). 5. IGF-I is the most likely factor which increases mammary gland synthetic capacity in response to somatotropin treatment, and thus is responsible for the galactopoietic effect of this hormone being exerted. 6. However, serum IGF-I may primarily be involved in regulation of nutrient partitioning during normal lactation, but a paracrine synthesis with local effect on the mammary gland cannot be ruled out.

Animals↗

Clinical and biological significance of carcinoma in situ of the testis.

Carcinoma in situ (CIS) of the testis is a preinvasive lesion that with time progresses into invasive germ cell tumour. CIS precedes all types of germ cell tumours except spermatocytic seminoma. An increased risk of harbouring CIS has been reported in men with a history of cryptorchidism, in contralateral testes of men previously treated for unilateral germ cell tumour, in intersex patients, in men with assumed extragonadal germ cell tumour and possibly in infertile men. CIS develops into invasive germ cell cancer in 50% of untreated patients within five years of diagnosis, and it is believed that with time CIS will progress into germ cell cancer in almost all patients. A testicular biopsy is necessary to diagnose CIS. Cells with the characteristics of CIS cells have been detected in seminal fluid, and it may be possible to develop methods for diagnosing the condition by analysis of the semen. We recommend orchidectomy as the treatment of choice in cases of unilateral CIS, if the other testis has a potential for fertility. In other cases, such as patients with testicular tumour and CIS of the contralateral testis, we recommend localized irradiation of the testis with CIS. Leydig cell function seems to be slightly impaired, but sufficient for sexual function, after irradiation. CIS cells show morphological and immunohistochemical similarities with primordial germ cells (gonocytes), whereas they share only few features with spermatogonia. Therefore, we suggest that CIS cells are malignant cells derived from gonocytes during embryonic development.

Carcinoma in Situ↗

Carcinoma in situ of the testis. Detection of malignant germ cells in seminal fluid by means of in situ hybridization.

Testicular germ cell tumors can be prevented if the neoplasia is diagnosed at the stage of carcinoma in situ (CIS). Hyperdiploid DNA content is one of the markers of CIS germ cells. We developed a noninvasive procedure for detection of CIS of the testis by means of a nonradioactive in situ hybridization assay with a probe for chromosome 1. Seminal cytospin smears from 2 men with isolated CIS changes, from 6 men in whom CIS was combined with a tumor, and from 16 control men without evidence of testicular neoplasia were tested. Ejaculates from men with CIS contained on average 2.6% hyperdiploid cells, whereas the corresponding percentage in the smears from controls was 0.2 (P = 0.009). In a blind study we identified samples from both patients with isolated CIS changes and from 3 of the 6 men in whom CIS was accompanied by a tumor, based on the percentage of the hyperdiploid cells. No false-positive results were obtained. Thus this study confirmed findings of previous immunocytochemical and flow cytometric studies that indicated exfoliation of CIS germ cells into seminal fluid. For detection of aneuploid cells in semen, in situ hybridization may be a more sensitive technique than flow cytometry. Applied on seminal samples, in situ hybridization may become a valuable and fast tool for diagnosis of CIS and thereby for prevention of testicular cancer.

Adult↗

Prevalence of carcinoma in situ and other histopathological abnormalities in testes of men with a history of cryptorchidism.

The incidence of invasive testicular cancer is increased in men with a history of cryptorchidism. Previous studies based on relatively small series indicated that the risk of carcinoma in situ of the testis also is increased in these men. In our study 500 consecutive men 20 to 30 years old, who were previously admitted to a department of surgery with the diagnosis of testicular maldescent, were asked to participate in a screening for carcinoma in situ of the testis. Of the men 300 consented to testicular biopsy. The biopsies were evaluated by light microscopy for carcinoma in situ and other histopathological abnormalities. Carcinoma in situ was diagnosed in 5 patients (1.7%, 95% confidence limits 0.5 to 3.9%). However, the true risk of carcinoma in situ might be higher, since 2 men who had been treated for testicular cancer before they were offered biopsy were excluded from the study. Advanced spermatogenesis, including the spermatid stage in all tubules, was found in biopsy specimens from only 37% of the men. In 80% of these specimens even the number of late spermatids was decreased. Thus, our study, based on a large number of testicular biopsies from an unselected group of men with testicular maldescent, provided further evidence that these men have an increased risk for carcinoma in situ of the testis. Our data combined with the results of other Scandinavian studies indicate that the true prevalence of carcinoma in situ in men with a history of cryptorchidism is approximately 2 to 3%. Additionally, we confirmed that spermatogenic function is severely impaired in maldescended gonads. Invasive testicular cancer can be prevented if the neoplasm is detected at the stage of carcinoma in situ. In our opinion the magnitude of prevalence of carcinoma in situ found in men with a history of cryptorchidism justifies that these men should be offered testicular biopsy when they reach adulthood.

Adult↗

A novel maturation marker for human Sertoli cells.

The maturation of Sertoli cells at puberty is critical for the initiation and maintenance of spermatogenesis. Little is known about the factors which control Sertoli cell maturation. We have examined Sertoli cells in testicular specimens from 44 subjects, ranging in age from 6 months to 67 years, for reactivity with a mouse monoclonal antibody (M2A) using the immunoperoxidase reaction. We found positive reactivity with prepubertal but not postpubertal Sertoli cells, suggesting that the antigen defined by M2A was a marker of immature Sertoli cells. This marker may be useful for studying the factors which influence Sertoli cell maturation during development of the testis.

Adolescent↗

Carcinoma in situ of the testis: aneuploid cells in semen.

The content of cellular DNA in ejaculates from eight patients with carcinoma in situ of the testis and 26 controls without evidence of testicular neoplasia was studied by flow cytometry. An aneuploid cell population with a ploidy value similar to that found for carcinoma in situ cells was detected in seminal fluid from four of the eight men with carcinoma in situ but in none of the controls. One year after orchidectomy or local irradiation in these four men no aneuploid cells were found in the semen. These findings show that a detectable proportion of malignant germ cells may be released into the seminal fluid of patients with carcinoma in situ of the testis. Analysis of seminal fluid may therefore aid in screening for early neoplasia of the testis.

Adult↗

A monoclonal antibody as a marker for carcinoma in situ germ cells of the human adult testis.

Carcinoma in situ of the testis (CIS) is a precursor of invasive testicular germ cell tumours. The diagnosis of CIS is however often missed when conventional histological techniques are used. No specific immunological marker for CIS germ cells of the testis has been demonstrated previously. A novel monoclonal antibody, M2A, reacting with malignant germ cells of seminomas has recently been developed. Using the immunoperoxidase reaction on tissue sections, we tested the reactivity of M2A with CIS germ cells of the human adult testis. Positive reaction was found in 19 of 20 testicular specimens showing CIS, whereas no staining was found in 39 testicular biopsies without CIS. Thus, M2A may serve as a diagnostic marker in detection of CIS germ cells.

Adult↗

Serum bone Gla-protein as a marker of bone growth in children and adolescents: correlation with age, height, serum insulin-like growth factor I, and serum testosterone.

Serum bone Gla-protein (BGP) was determined by RIA in 450 normal children (229 girls and 221 boys, aged 6-19 yr). Serum BGP concentrations changed in relation to age and sex with a pattern that resembles the height velocity curves for children. The increase in serum BGP occurred at the expected age of the growth spurt in both sexes, and the peak values occurred at the age of 12 yr in girls [mean, 49.2 +/- 5.6 (+/- SE) micrograms/L] and 14 yr in boys (64.0 +/- 6.3 micrograms/L). In the boys aged 10-14 yr and in the girls aged 9-12 yr, serum BGP correlated significantly with serum insulin-like growth factor I (IGF-I), serum testosterone, age and height. When the interrelationship was analyzed by means of partial correlation, with age held constant, serum BGP still correlated significantly with the other parameters, but when height was fixed there was only a correlation with serum IGF-I. In children with untreated central precocious puberty, the mean serum BGP concentration was significantly higher than in age-matched normal children [mean, 61.4 +/- 31.7 (+/- SD) vs. 29.0 +/- 10.3 micrograms/L; P less than 0.001]. Serum BGP values decreased significantly in these patients during 1 yr of treatment with a LHRH analog (buserelin) and cyproterone acetate. We conclude that serum BGP is a sensitive marker of bone growth in normal children and in children with increased growth velocity. Repeated measurements may provide useful information in the diagnosis and treatment of children with disturbances in bone turnover.

Adolescent↗

Testicular cancer risk in boys with maldescended testis: a cohort study.

Testicular maldescent is considered as a predisposing condition for development of testicular malignancy. Male subjects with a history of cryptorchidism have been suggested by some authors to have a 40 to 50 times increased risk of testis cancer. However, the magnitude of this risk is a point of considerable disagreement. Therefore, we studied the records of 506 consecutive patients hospitalized for maldescended testis from January 1949 to December 1960. Testis cancer developed in 6 patients, which when compared to the 1.3 expectant Danish incidence rate, yielded a statistically significant relative risk of 4.7 (95 per cent confidence interval 1.7 to 10.2). Thus, our study confirmed that male subjects with a history of testicular maldescent have an increased risk for testis cancer, although the magnitude of this risk was lower than suggested previously.

Adult↗

Investigation of the criteria for assessing the outcome of treatment in acromegaly.

The outcome of treatment in acromegaly is usually assessed by measuring plasma concentrations of growth hormone (GH)--either basal spontaneous levels or during hyperglycaemia. There is no consensus on how cure should be defined. Many studies have considered basal plasma growth hormone concentrations below 20 mU/l (10 ng/ml) as proof of cure, although some recent studies have applied lower values. At present a limit of 10 mU/l (5 ng/ml) seems to be accepted as evidence of cure. We have studied 28 acromegalic patients after transsphenoidal adenomectomy. Plasma GH concentrations (basal and during hyperglycaemia) as well as plasma somatomedin C (SMC) concentrations were measured and compared to the clinical symptoms. There was a close correlation between plasma GH and SMC concentrations (except when plasma GH levels were low) and between the clinical assessment and SMC concentrations. Very low plasma GH levels (less than 1 mU/l or 0.5 ng/ml) were associated with normal SMC values and clinical cure, high GH levels (greater than 10 mU/l or 5 ng/ml) with elevated SMC levels and persisting acromegaly. Moderately elevated plasma GH concentrations (1.9-9.6 mU/l) did not allow any conclusions on the outcome of treatment as assessed from SMC determinations and clinical evaluation. It is concluded that the usual criteria for cure in acromegaly may not be sufficiently strict.

Acromegaly↗

Carcinoma-in-situ of the testis: possible origin from gonocytes and precursor of all types of germ cell tumours except spermatocytoma.

Based on evidence from morphological and histochemical studies and from clinical experience, the following hypotheses are proposed: carcinoma-in-situ (CIS) germ cells are malignant gonocytes; these CIS gonocytes have some capacity to regress into more primitive, totipotent embryonic cells which can give rise to all types of nonseminomatous germ cell tumours; the tumour germ cells of classical seminomas are malignant gonocytes derived from CIS gonocytes which have lost their ability to regress into totipotent embryonic cells; the ability of CIS gonocytes to regress into totipotent embryonic cells decreases with age, whereas the capacity to form classical seminoma cells is preserved; the transformation of CIS gonocytes into invasive tumours is dependent on factors such as gonadotrophins and/or testicular steroids; the pathogenesis of classical and spermatocytic seminoma are unrelated. As a consequence of these hypotheses an alternative nomenclature for carcinoma-in-situ, seminoma and dysgerminoma is suggested.

Carcinoma in Situ↗

Screening for carcinoma-in-situ of the testis.

Germ cell neoplasia detected at the preinvasive stage of carcinoma-in-situ (CIS) can be cured by orchidectomy or by localized irradiation of the testis. Therefore, screening for carcinoma-in-situ of the testis has been applied to groups of individuals known to have an increased risk of testicular cancer. A high (5.5%) incidence of CIS was found in the contralateral testis of men with a unilateral cancer of the testis. An increased incidence of CIS was also found among men with a history of cryptorchidism. We recommend routine screening for CIS of the testis in both groups of men. The role of screening for CIS among subfertile men remains to be elucidated.

Biopsy↗