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Biomedical subjects

P Alm

Publications and source records attributed to P Alm.

At least 127 records · Page 7Linked to original sources

Inhibition of islet nitric oxide synthase increases arginine-induced insulin release.

NG-Nitro-L-arginine, an inhibitor of nitric oxide (NO) synthase, markedly (+50%) increased the L-arginine-induced insulin release from isolated mouse islets but did not itself influence insulin secretion. An abundance of mouse islet cells were positively stained for the enzyme NADPH diaphorase, which reportedly is a marker for NO synthase. The data suggest that the NO synthase activity in mouse islet tissue may inhibit insulin secreting processes and that L-arginine has a dual action on insulin release.

Amino Acid Oxidoreductases↗

The retinoblastoma gene in breast cancer: allele loss is not correlated with loss of gene protein expression.

The significance of the retinoblastoma gene (RB) in the development of human breast cancer remains unclear. In the present study, loss of heterozygosity (LOH) in RB was found in 26% of 90 informative primary breast tumors and was correlated to DNA nondiploidy, a high S-phase fraction, and LOH at chromosome 17p13.3. However, allele loss was not associated with loss of RB protein (pRB) expression. Low to absent levels of pRB were found in 15% of 73 immunoblot analyzed tumors, most of which manifested retained heterozygosity in RB. Conversely, tumors exhibiting LOH showed often high pRB expression. Our data suggest that RB may be involved in the pathogenesis of some breast tumors, as evidenced by the absence of pRB, but that this alteration is acquired by mechanisms other than the unmasking of a recessive mutation by allele loss. LOH in RB may be merely a stochastic event in the unstable genome of aneuploid, rapidly proliferating cells or, alternatively, reflect the presence of an adjacent tumor suppressor gene.

Adult↗

Neuroendocrine differentiation in male breast carcinomas.

The presence of neuroendocrine differentiation, as expressed by cellular chromogranin immunoreactivity, was investigated in paraffin-embedded tissue material from 51 consecutive cases of male breast carcinoma. From six of these cases electron microscopic studies were included. Chromogranin-immunoreactive cells were present in solid cords and delineated tubular structures. Ultrastructurally, dense core secretory granules could be detected. The expression of neuroendocrine differentiation was 45%, which is between two and eight times higher than reported for female breast carcinomas by other investigators. The present findings suggest that male breast carcinoma is an exclusive tumour disease showing both similarities and discrepancies when compared to its female counterpart.

Adult↗

Functional effects, binding sites and immunolocalization of endothelin-1 in isolated penile tissues from man and rabbit.

Functional effects of endothelin-1 (ET-1) were investigated in isolated preparations of human and rabbit corpus cavernosum (CC) and human penile circumflex veins (CV). In all preparations, ET-1 induced slowly developing, concentration-dependent contractions. The threshold concentration of ET-1 in CV was approximately 10 and 112 times lower than the threshold concentrations in human and rabbit CC, respectively. Furthermore, the contractions in CV reached a defined maximum at 10(-7) M ET-1 (-log EC50 = 9.12 +/- 0.17), whereas no maximum was obtained in CC preparations within the concentration range used (less than or equal to 3 x 10(-7) M). Pretreatment with the Ca++ channel blocker nimodipine partly reduced the ET-1-induced contractions in human and rabbit CC, but had no significant effect on CV preparations. In a Ca(++)-free medium containing the chelator ethyleneglycol-bis-(beta-aminoethylether)-N,N'-tetra-acetic acid, the contractions induced by ET-1 were reduced, but not abolished, in all preparations. The contractions induced by ET-1 are thus mediated mainly by influx of Ca++, although there seem to exist differences in the relative contribution of L-type Ca++ channels in CC and CV. Furthermore, additional mechanisms beside Ca++ influx are likely to be involved in both tissues. A high density of [125I]ET-1 binding sites was observed throughout the stroma and in the muscle layer of the deep penile artery in both human and rabbit CC. In the human CV, numerous binding sites were observed, but no clear difference between the various structures of the vessel wall could be detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Urine and serum levels of the carboxyterminal domain (NCl) of collagen IV in membranous glomerulonephritis and diabetic nephropathy.

Serum and urinary concentrations of NCl, the non collagenous globular domain of collagen IV, were used as markers for turnover of basement membranes. NCl levels were studied in membranous glomerulonephritis and diabetic nephropathy. Thirteen patients with membranous glomerulonephritis and 8 insulin-dependent diabetic patients with diabetic nephropathy were compared to 16 apparently healthy control subjects. The patients with membranous glomerulonephritis had lower levels of NCl in serum and urine compared to the control subjects. In comparison, the patients with diabetic nephropathy had similar levels of NCl in serum and urine as the control subjects. Furthermore, among patients with membranous glomerulonephritis, those with hypertension had higher serum levels of NCl than those without, which may indicate that hemodynamic factors influence the basement membrane collagen metabolism. It is suggested that there are differences in basement membrane turnover in membranous glomerulonephritis and diabetic nephropathy although there are similarities in glomerular histopathological features. Other possible mechanism are discussed. Further studies are needed to confirm the suggested mechanism.

Adult↗

Innervation of the human uterine artery and contractile responses to neuropeptides.

The intrinsic innervation of the human uterine artery was investigated histochemically, and the motor responses to some of the demonstrated peptides and other humoral factors were studied on isolated vascular preparations. There were nerves with specific immunoreactivities for tyrosine hydroxylase, dopamine beta-hydroxylase, neuropeptide-Y (NPY), vasoactive intestinal peptide (VIP) and peptide histidine methionine, and enzymatic reactivity for acetylcholine esterase. The most effective stimulator of smooth muscle contractility was arginine vasopressin followed in order by oxytocin, noradrenaline together with NPY, noradrenaline alone and dopamine. No effect was seen with acetylcholine and tyrosine, and VIP caused inconsistent relaxation of contractile activity induced by PGF2 alpha. These results suggest that the uterine blood flow is regulated by complex interactions of factors, some occurring in nerve terminals and some being circulating humoral factors.

Adult↗

Differences in vasomotor responses between main stem and smaller branches of the human uterine artery.

Specimens of the human uterine artery and its branches were taken at hysterectomy. By microscopical dissection, three groups of arteries were obtained with respect to size-main stem, medium and small branches (inner diameters of greater than 1, 0.6-0.8 and less than 0.4 mm, respectively). The contractile effects of different vasoactive substances were studied and the responses expressed as percentages of that of K(+)-depolarization calculated. The most potent vasoconstrictor (the lowest EC50 concentration) was arginine vasopressin (AVP) followed in order by endothelin, oxytocin, prostaglandin (PG)F2 alpha, noradrenalin and dopamine. Angiotensin had inconsistent effects. Atrial natriuretic peptide (ANP) counteracted the contractile effects of endothelin. AVP, endothelin, oxytocin and noradrenalin were significantly more potent on the smallest branches than on the main stem of the artery. Since the former type of vessel represents resistance arteries, the present results suggest that AVP, endothelin, oxytocin and noradrenalin could be of specific importance in the regulation of uterine blood flow. PGF2 alpha, dopamine and angiotensin appear to be of minor importance from this aspect but ANP could play a role by regulating the effects of endothelin.

Adult↗

A 16-year-old girl with invasive carcinoma of the vulva.

We present a 16-year-old girl with vulvar squamous cell carcinoma. The patient initially received a radical treatment because of lymph-node dissemination. However, recurrent disease erupted a little more than one year after the initial treatment, with metastases in the right lung and multiple osteolytic skeletal metastases. Despite aggressive treatments with chemotherapy the patient died about 2 years after the initial diagnosis. An aggressive radical treatment must be chosen for cases of invasive vulvar carcinoma, irrespective of the patient's age.

Adolescent↗

Influence of "nuclear" estrogen receptor content on prognosis of early stage carcinoma of the uterine body. A short-time follow-up.

Sixty-five patients with Stage I and II endometrial carcinoma were investigated. After a short-time follow-up (17-24 months) significant differences in frequency of relapses were observed between patients with tumors containing low amounts of estrogen receptor (ER less than 60 fmol/mg DNA) in the nuclear pellet, and those with tumors containing greater than 60 fmol ER/mg DNA (p = 0.01). Other prognostic factors showed no differences in frequency of relapses. In this small patient material with a short-time follow-up we therefore suggest that ER in the nuclear pellet may be an important prognostic factor.

Adenocarcinoma↗

Effect of moderate protein-deficiency on ultrastructure in parotid and submandibular acinar cells in the adult rat.

Powdered diets, of three different levels of protein, were given to groups of adult male rats for 21 days. Two diets with reduced protein content, 5% or 10% casein, were given to experimental rats. A diet with an adequate protein content, 20% casein, was given to controls. A reference group of rats was fed a standard pellet diet for the same period. At the end of the experimental period, the parotid and the submandibular glands were removed and subjected to electron microscopy. The zymogen granules of acinar cells in the parotid glands from the rats receiving the 5% protein diet had lost their normal opaqueness and turned electron lucid whereas parotid glands from the rats fed the 20%, the 10%, and the standard pellet diet exhibited normal acinar cells. The ultrastructure of submandibular acinar cells was not affected in any dietary group.

Animals↗

Prognostic value of steroid receptor concentration and flow cytometrical DNA measurements in stage I-II endometrial carcinoma.

In order to make a more individualized therapy possible in endometrial cancer we investigated the prognostic ability of steroid receptor concentration and the DNA content in individual cells as measured by flow cytometry. We found that although the steroid receptor concentration was a prognostic parameter, the DNA content proved to be a better parameter than all other known prognostic parameters in endometrial carcinomas stage I-II. Thus it was possible to divide the tumors into three groups; 1) diploid tumors with a relapse rate of 6%, 2) aneuploid tumors with a high estradiol receptor concentration and without myometrial invasion of more than the inner third, and with a relapse rate of 18%, 3) aneuploid tumors, poorly differentiated with a low estradiol receptor concentration or myometrial invasion and with a relapse rate of 44%.

Adult↗

Local mechanical effects and humoral factors evoke degeneration of guinea pig uterine innervation.

Small porcelain pellets were inserted into one of the uterine horns of virgin guinea pigs. Mating caused pregnancies only in contralateral, non-pellet-containing uterine horns. The number and morphology of uterine nerve structures was studied immunohistochemically. In pellet-surrounding tissues of virgin animals the number of nerves was reduced and remaining nerve structures displayed signs of degeneration. This nerve reduction was further advanced in early to mid-pregnancy when almost no nerve structures could be detected. Myometrial strips were transplanted to the anterior eye chamber and became reinnervated by adrenergic nerves. The pattern and structure of the adrenergic reinnervation did not differ between strips taken from virgin animals, untreated or following chemical sympathectomy, or taken from primiparous animals following pregnancy induced sympathectomy. The adrenergic reinnervation of transplants from virgin animals was not affected by pregnancy of the recipient animal. It is suggested that the uterine innervation can be influenced by local, mechanically-induced effects, which during pregnancy co-operate with conceptus-related humoral factors to cause an almost total uterine nerve degeneration. The ability of uterine adrenergic reinnervation is probably not significantly influenced by local environmental tissue factor(s), but is related rather to extent of nerve damage.

Animals↗

Estrogen receptor content in nuclear pellet from adenocarcinoma corporis uteri biopsies.

Ninety-one patients with Stage I and II endometrial carcinoma were investigated. Biopsy material obtained prior to primary treatment was analyzed for contents of estrogen (ER) and progesterone (PgR) receptors, and the values of these were related to the degree of malignancy. ER content in the nuclear pellet was decreased at increased tumor anaplasia.

Adenocarcinoma↗

Evaluation of peritoneal tube grafts in the inferior vena cava of the pig.

A tube graft 2.5 or 5 cm long, was constructed from the peritoneum of the anterior abdominal wall of 12 pigs. It was anastomosed end-to-end as an interposition graft in the infrarenal vena cava. The observation period was 4 months. Three of the six short grafts were venographically patent at 2 weeks, while all the long grafts were occluded. After 4 months two short grafts had recanalized, giving a patency rate of five out of six short grafts. No long grafts recanalized. In three of the patent specimens no clear tissue changes were found with light microscopy, while in the others changes of inflammation and fibrosis were noted. Scanning electron microscopy revealed good 'endothelialization' in two specimens, and partial 'endothelialization' in the others. No dilatation or severe stenosis of the patent grafts was seen. The occluded grafts remained only as a fibrous strand with sutures.

Anastomosis, Surgical↗

Co-existence and origin of peptidergic and adrenergic nerves in the guinea pig uterus. Retrograde tracing and immunocytochemistry, effects of chemical sympathectomy, capsaicin treatment and pregnancy.

The occurrence and distribution of peptidergic nerves in the guinea pig uterus was studied by means of immunocytochemistry using numerous neuropeptide anti-sera. Neuropeptide Y (NPY)-immunoreactive (IR) nerves were the most abundant, whereas substance P (SP)-, calcitonin gene-related peptide (CGRP)-, and neurokinin A (NKA)-IR nerves were less frequent, and peptide histidine isoleucine (PHI)-IR nerves were the most sparse. Chemical sympathectomy by means of 6-hydroxydopamine, and capsaicin treatment revealed the division of the peptidergic nerves into three separate populations: (1) NPY-IR nerves, which co-existed with adrenergic nerves, (2) SP-, CGRP- and NKA-IR nerves, which mutually co-existed, and (3) PHI-IR nerves. Parallel-running adrenergic/NPY-IR and SP-IR nerves could be found with very similar although not completely identical morphological appearance. Paracervical ganglia contained neurotensin- and dynorphin A-IR cells bodies in addition to cell bodies with immunoreactivities similar to those in prevertebral ganglia. Combined retrograde tracing with True blue and immunocytochemistry showed that the adrenergic and NPY-IR uterine nerves originate in paracervical and prevertebral ganglia. In the prevertebral ganglia the cellular origin was the same for adrenergic and NPY-IR nerves. In contrast, SP-, CGRP-, and NKA-IR nerves originated in dorsal root ganglia. At full-term pregnancy all the neuropeptide immunoreactivities had vanished, probably reflecting a fetus-induced general nerve degeneration.

Adrenergic Fibers↗

Protein gene product 9.5 (PGP 9.5). A new neuronal marker visualizing the whole uterine innervation and pregnancy-induced and developmental changes in the guinea pig.

The guinea pig uterus is supplied by different populations of nerves which can be demonstrated by specific immunocytochemical and histochemical techniques. So far, there has been no single marker displaying entire peripheral innervation patterns. Recently, protein gene product (PGP) 9.5, a cytoplasmic protein in neurons and neuroendocrine cells, was found to visualize both different populations and subtypes of nerves. This prompted the present study of using PGP 9.5 for visualization of the whole uterine innervation. This was performed by the indirect immunofluorescence method using antiserum to PGP 9.5 raised in rabbits. PGP-immunoreactivity was present in all neuronal parts of the extrinsic and intrinsic uterine innervation, including different subpopulations of nerves. This was verified by chemical sympathectomy and sensory denervation with 6-hydroxydopamine and capsaicin-treatment respectively, and double immunostaining. By term a disappearance of uterine PGP-nerve-immunoreactivity was observed which was almost complete in fetus-bearing uterine tissue and further strengthens previous assumptions of a general, pregnancy-induced uterine neuronal degeneration. The developmental time-course and morphology of PGP-immunoreactive nerve structures was similar to that for other neuronal markers and support the suggestion of PGP-immunoreactivity as a general marker for the entire uterine innervation, and suggests that the presence of PGP 9.5-immunoreactivity may coincide with functional maturation of uterine innervation.

Animals↗