Biomedical subjects

W Jacobson

Publications and source records attributed to W Jacobson.

At least 19 recordsLinked to original sources

PubMed1997

Effect of amiodarone on the lung shown by polarized light microscopy.

OBJECTIVE: To show lipid deposits in the lung of patients treated with amiodarone. MATERIALS AND METHODS: Formalin-fixed, unstained frozen sections were used to reveal lipid deposits by means of polarized light. Lung tissues obtained at the postmortem examination of one patient and the surgical biopsy of another were available. RESULTS: Birefringent lipid deposits were seen in the alveolar lining cells and macrophages, as well as in the walls of arterioles and venules. CONCLUSIONS: To assess the effect of amiodarone on the lung, polarized light microscopy of unstained, frozen sections is a simple and rapid method.

Amiodarone↗

PubMed1995

Localisation of androgen receptors in dermal fibroblasts, grown in vitro, from normal subjects and from patients with androgen insensitivity syndrome.

Human genital skin fibroblasts show the androgen receptor (AR) as bright red granules (0.5 micron in diameter) after treatment with one (of 3) primary polyclonal antibody and a secondary antibody linked to alkaline phosphatase. Almost all AR were cytoplasmic in 12 normal strains and in 8 strains from patients with partial (PAIS) and 6 with complete androgen insensitivity syndrome (CAIS). When 25.8 nM 5-alpha-dihydrotestosterone (DHT) or methyltrienolone was added to the medium, some AR were translocated into the nucleus in 13 experiments with 8 strains of normal fibroblasts; of 8 strains of patients with PAIS 3 failed to translocate to a detectable extent in the presence of androgen in the medium and none of the 6 strains from patients with CAIS translocated.

Androgens↗

PubMed1994

Predicting and optimizing success in an intra-uterine insemination programme.

We analysed 381 consecutive cycles of homologous intrauterine insemination (IUI) in 215 infertile couples, resulting in 48 pregnancies (12.6%/cycle, 22.3%/patient). Cycle fecundity ranged from 0.11 to 0.14 in women aged 25-39 years, falling to 0.04 beyond age 40 years. Of the 48 pregnancies, 43 occurred in the first three treatment cycles, in which fecundity was 0.14, 0.16 and 0.10 respectively. Beyond three cycles, fecundity was 0.07 (P = 0.05 versus first two cycles). The occurrence of pregnancy varied with diagnosis (P = 0.04). Fecundity was significantly greater for women with ovulatory dysfunction (0.30) than for endometriosis, male factor, tubal factor, idiopathic infertility or multifactorial (0.08-0.14). Ovulation induction using menopausal gonadotrophins offered significant advantage over natural cycles or cycles using clomiphene citrate without gonadotrophins (0.15 versus 0.03, P = 0.01). Cycles in which pre-ovulatory surges were either induced or supported with human chorionic gonadotrophin (HCG) were superior to spontaneous luteinizing hormone surges (0.13 versus 0.03, P = 0.05). Recruitment of at least two mature (> 1.6 cm) follicles was critical. Only one pregnancy occurred in 64 cycles characterized by one mature follicle, compared with a pregnancy rate of 0.15 in cycles characterized by two or more mature follicles (P = 0.006). IUI is not beneficial to women > 40 years old, and has the best chance of success within three cycles. Multiple follicle recruitment using gonadotrophin-based stimulation protocols and mid-cycle HCG are necessary to achieve an acceptable pregnancy rate.

Adult↗

PubMed1993

Rapid visualization of NMDA receptors in the brain: characterization of (+)-3-[125I]-iodo-MK-801 binding to thin sections of rat brain.

We have developed and characterized a method for the rapid autoradiographic determination of receptor sites for the non-competitive NMDA receptor antagonist, MK-801, using an iodinated form of the compound, (+)-3-[125I]-iodo-MK-801. The binding site was shown to exhibit those criteria necessary for its definition as a receptor site, i.e., the binding was saturable, of high affinity, easily reversible, and stereospecific. Saturation analysis of binding to thin brain sections revealed a Bmax of 108.1 +/- 10.5 fmol/mg protein and a Kd of 383 +/- 67 pM. The pharmacology of the interaction of the ligand with the binding site yielded good correlation between the potency of various substances to complete for the binding site and their ability to act as antagonists of NMDA. Autoradiographs of thin coronal brain sections using (+)-3-[125I]-iodo-MK-801 yielded high quality images in 24-48 h with a distribution of binding sites paralleling that reported for the tritiated form of the ligand, i.e., with high densities in the hippocampus, cerebral cortex and lateral septum. Other areas with significant binding included parts of the thalamus, the amygdala and the olfactory tubercules. Furthermore, due to its high specific activity, this ligand lends itself to the study of regions not rich in MK-801 binding sites, such as the diencephalon.

Animals↗

PubMed1993

Surfactant and adult respiratory distress syndrome.

In order to determine if the Adult Respiratory Distress Syndrome (ARDS) is associated with a shortage of pulmonary surfactant, we have examined a series of 155 undiluted tracheal aspirates obtained from 23 patients with ARDS and from 30 patients without ARDS, all 53 needing ventilatory support. The unfixed and unstained specimens were examined by polarized light microscopy for the presence of pulmonary surfactant. Free surfactant particles were present in the aspirates of 50 patients (95%). Within minutes of obtaining the specimen, in addition to showing surfactant, the examination of these undiluted, unfixed tracheal aspirates by light microscopy showed the presence of bacterial and fungal infection. As fibrinogen/fibrin inactivates surfactant, the undiluted aspirates of 21 patients with ARDS and of 30 patients without ARDS were stained for the presence of these proteins by a new slide method using 0.01 ml of tracheal aspirate. Fibrinogen/fibrin was found in the aspirates from 20 of 21 patients with ARDS and in only five of 30 patients without ARDS; these five had bronchopneumonia. The method has a sensitivity of 0.95 and a specificity of 0.83. The role of plasma proteins and of neutrophil leucocytes in causing ARDS is discussed.

Adolescent↗

PubMed1993

Serum folate and chronic fatigue syndrome.

We assayed serum folate levels of 60 patients with chronic fatigue syndrome (CFS) and found that 50% had values below 3.0 micrograms/l. Some patients with CFS are deficient in folic acid.

Adolescent↗

PubMed1992

Microscopic observations on tracheal aspirates from ventilated neonates. II. The onset of bronchopulmonary dysplasia and other changes.

A total of 450 undiluted and unprocessed tracheal aspirates from 120 intubated infants were examined microscopically for evidence of bronchopulmonary dysplasia and other changes. In 19 infants desquamated sheets of dysplastic epithelium in the fresh aspirate provided an early indication of developing bronchopulmonary dysplasia. Examination of unstained tracheal aspirates can provide, within minutes, information not only about the onset and development of bronchopulmonary dysplasia, but also provide evidence for milk or formula aspiration and for gastro-oesophageal reflux.

Bile Pigments↗

PubMed1990

Gonadotropin suppression with oral contraceptives before in vitro fertilization.

One hundred eighty-one stimulation cycles in which gonadotropin suppression with oral contraceptives (OCs) preceded induction of follicle stimulation (study group) and 113 stimulation cycles without pituitary suppression (control group) were compared. The mean length of ovarian suppression was 35.3 +/- 0.9 days. No spontaneous luteinizing hormone (LH) surges occurred when the use of OC preceded ovarian hyperstimulation, whereas in the control group the incidence of LH surges was 19.5%. The mean amount of human menopausal gonadotropin required was significantly lower in the study group than in the control group (8.9 +/- 0.4 and 10.9 +/- 0.4 ampules, respectively). Significantly more follicles greater than or equal to 1.5 cm in diameter were seen on the day before oocyte retrieval and significantly more oocytes were retrieved per attempt in the group with OC pretreatment. Our data clearly demonstrate that OCs are useful in vitro fertilization stimulation protocols to facilitate scheduling of cycles and to prevent spontaneous LH surges.

Abortion, Spontaneous↗

PubMed1989

Endometrial thickness and growth during ovarian stimulation: a possible predictor of implantation in in vitro fertilization.

The present study was undertaken to evaluate endometrial thickness and the amount of endometrial growth (delta) in patients who conceived during in vitro fertilization (IVF) (n = 36) compared with matched women who did not conceive (n = 72). Estradiol (E2) and endometrial thickness were measured daily from cycle day 10 to the day after human chorionic gonadotropin (hCG). Mean endometrial thickness and E2 levels on cycle day 10 did not differ. On the day before ovum retrieval, significantly thicker endometrium was observed in the pregnant than in the nonpregnant women (8.6 +/- 0.3 [SEM] and 7.1 +/- 0.3 mm, respectively; P less than 0.0005), whereas the mean E2 levels did not differ. The delta endometrial growth was greater in the women who conceived than in the nonpregnant group (4.3 +/- 0.2 and 2.5 +/- 0.2 mm, respectively; P less than 0.0005). The fertilization rate and serum E2 levels did not correlate with endometrial thickness nor with delta endometrial growth. Our data suggest that the amount of endometrial growth during ovarian hyperstimulation and the endometrial thickness on the day before oocyte retrieval deserve further study as possible predictive parameters for implantation.

Embryo Implantation↗

PubMed1989

Decreases in mediobasal hypothalamic and preoptic area opioid ([3H]naloxone) binding are associated with the progesterone-induced luteinizing hormone surge.

In view of evidence implicating hypothalamic opioid systems in the control of LH release, we have examined the binding of [3H]naloxone (NAL) to slices of mediobasal hypothalamus (MBH) and preoptic area (POA) during the induction of an afternoon LH surge (1630-1700 h) in estradiol benzoate (EB)-primed ovariectomized (OVX; day 0) rats by treatment with progesterone (P; day 2). Such a surge was invariably accompanied by a decrease from early morning (1000 h) values in the number of NAL-binding sites detectable in the MBH, while the affinity of the binding site was not affected over the course of the day. Time-course studies indicated that P injection at 1000 h on day 2 was followed by a transient midday elevation in the amount of NAL bound to slices of MBH; the binding decreased significantly before the onset of and during the LH surge. A similar diurnal change was not observed in MBH slices of either oil-treated OVX rats (controls) or EB-treated OVX rats, which displayed only a 2-fold increase in LH release in the afternoon. Further studies indicated a similar change in NAL binding to slices of the POA of EBP-treated rats. Since hypothalamic opioid systems inhibit LH release, the decrease in opioid binding to MBH as well as POA slices suggests that P may curtail the existing opioid inhibitory influence in these areas before and during the course of the afternoon LH surge.

Animals↗

PubMed1988

Effects of the noradrenergic neurotoxin DSP4 on growth and the gonadal steroid- and PMSG-induced release of LH in the prepubertal female rat.

We have examined the effect of DSP4 treatment on PMSG-induced ovulation. A marked attenuation of the stimulatory effects of PMSG (7.5 I.U.) by DSP4 was evidenced by the significantly lower number of corpora lutea present in the ovaries of those animals which ovulated compared to controls. In addition, ovarian weight was lower in the DSP4 group. In a further experiment, we examined the effect of DSP4 on the induction of an LH surge by progesterone (P) in estradiol benzoate (EB) primed rats. DSP4 administration 2 hours prior to P eliminated the LH surge seen in controls. In view of our previous observations that DSP4 can interact with opioid receptors, we attempted to block its inhibitory effect on PMSG and EB/P stimulations. Coinjection of naloxone, an opioid antagonist, only partially prevented the influence of DSP4. It seems likely, therefore, that opioid receptors are not involved in the inhibitory effects of DSP4 described here. In further experiments, we studied the effects of DSP4 on spontaneous sexual maturation in female rats. DSP4 was administered (50 mg/kg, IP) on either day 5, day 23, day 29, or both day 24 and day 26 of life. Growth was inhibited and vaginal opening (VO) was significantly delayed in all except the day 29 group. However, VO occurred at the same body weight as the controls. By the end of the experiment, hypothalamic noradrenaline levels were not significantly different between control and DSP4-treated animals. The lack of an effect of DSP4 on the progression to puberty may be due to sufficient recovery of the central noradrenergic systems during the time course of the experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1988

Tracheal aspirates from neonates during endotracheal intubation: detection of surfactant by polarized light microscopy.

A technique for detecting the presence of pulmonary surfactant in the tracheal aspirates obtained from preterm babies is described. The specimens were examined by means of polarized light microscopy. Surfactant could be simply and rapidly identified by its appearance as birefringent particles in volumes of aspirate as little as 1 microliter. Tracheal aspirate specimens from 108 babies, obtained on the first day of life, were examined without knowledge of the patient's clinical details. When the samples from each baby were subdivided into three groups on the basis of the amount of surfactant particles seen, this subgrouping corresponded well with the babies' ventilatory requirements at the time of sample collection. This method of detecting surfactant material may prove valuable in determining the degree of surfactant deficiency in individual preterm babies with respiratory illness.

Humans↗

PubMed1987

Serum folate in viral and mycoplasmal infections.

The concentration of serum folate in 260 patients with viral and mycoplasmal infections was determined (305 samples). In 60% the serum folate concentrations were found to be below 3 micrograms/l. The incidence of low serum folate varied slightly. According to the infections diagnosed, low values were: for influenza A 50% (50 patients), influenza B 42% (45 patients), human parvovirus 67% (76 patients), rubella 62% (13 patients), infectious mononucleosis 60% (15 patients), Mycoplasma pneumoniae 73% (45 patients). For a group of undiagnosed rashes it was 81% (16 patients). The cause of low concentrations of serum folate in these patients is discussed.

Female↗

PubMed1987

Biopterin in Parkinson's disease.

Tetrahydrobiopterin is an essential co-factor in the natural synthesis of dopamine. Oral tetrahydrobiopterin was given in small doses to four patients with early Parkinson's disease but had no discernible effect.

Adult↗

PubMed1986

Tissue slices in radioligand binding assays: studies in brain, pineal and muscle.

The use of tissue homogenates in receptor binding assays raises serious questions as to the physiological value of a preparation which examines receptors (binding sites) in disrupted tissue. In order to usefully study the regulatory properties of neurotransmitter receptors under physiological conditions, the necessity for tissue preparations which retain some degree of cellular integrity is clear. We review here the experiments which have utilized intact tissue - largely in the form of thick slices - to perform radioligand binding assays. There are many reports which note marked differences between studies in intact versus broken cell preparations. For example, significant discrepancies in KD and Bmax values are apparent for [3H] quinuclidinyl benzilate (muscarinic) and [3H] ouabain (Na+/K+-ATP ase, sodium pump) sites in brain and muscle respectively. A further example is the well-described stimulatory effect of GABA on benzodiazepine binding sites which is not seen in tissue slices. Other examples are highlighted. For all ligands so far examined, binding to slices is reversible, stereospecific, saturable, displaceable by appropriate drugs and of high affinity (nM). The method developed in our own laboratory is inexpensive, rapid and involves a minimum of tissue preparation. The technique is so simple as to allow many workers to enter this field who would not otherwise have done so. We suggest that metabolically active tissue slices offer the simplest approach to the study of cell-surface receptor regulation in living tissue.

Animals↗

PubMed1986

Brain opioid receptors in the hibernating bat, Myotis lucifugus: modification by low temperature and comparison with rat, mouse and hamster.

Several studies have provided evidence that brain opioid peptides may be involved in the control of the hibernation cycle. We have now examined the influence of hibernation on central opioid receptors. We have characterized the receptor binding properties of [3H]-naloxone in slices of the cerebral cortex and hypothalamus of the bat Myotis lucifugus. These receptors possess those characteristics expected of an opioid site namely high affinity, stereospecificity and saturability. Under normal incubation conditions (30 degrees C) we observed no effect of hibernation on [3H]-naloxone binding. However, when binding assays were performed at temperatures corresponding to the appropriate body temperature (e.g., 4 degrees C for hibernation) we detected a significant low temperature-induced increase in hypothalamic binding. Similar experiments in rat, mouse and hamster revealed that [3H]-naloxone binding was also increased at 4 degrees C when compared to 30 degrees C. This was true in hypothalamus and cortex. Additional studies in the rat demonstrated that the opioid receptor is of higher affinity at low temperatures. The behavioural and neurochemical consequences of this change in the opioid receptor, and whether this might be involved in the regulation of hibernation, remain to be studied.

Animals↗

PubMed1986

Association of diurnal variations in hypothalamic but not cortical opiate ([3H]-naloxone)-binding sites with the ability of naloxone to induce LH release in the prepubertal female rat.

We report the existence of a diurnal variation in the binding of the opiate antagonist [3H]-naloxone to slices of the mediobasal hypothalamus from prepubertal female rats. The binding is highest in the early morning and reaches a nadir in the late afternoon. Opiate binding in cortical slices from such animals is constant over the course of the day. Changes in receptor density, and not in receptor affinity, account for the diurnal variation in the amount of ligand bound. These diurnal variations in receptor numbers are associated with changes in the ability of naloxone to release LH and may be crucial in the transition from the juvenile state to one of competent reproductive functioning.

Animals↗

PubMed1985

Interstitial haemosiderin in the lungs of sudden infant death syndrome: a histological hallmark of 'near-miss' episodes?

The occurrence of multiple intrathoracic petechial haemorrhages in sudden infant death syndrome is well-documented and undisputed. We describe a study of 24 consecutive sudden infant deaths in which Perls' method for staining of iron in lung sections has been employed in addition to standard post-mortem procedures. Haemosiderin-containing macrophages have been demonstrated in 13 infants in subpleural and interstitial lung tissue in the absence of local fresh interstitial haemorrhage; ten of these infants had no evidence of respiratory tract inflammation and died mainly between one and three months of age. Eleven babies without haemosiderin showed evidence of inflammatory lesions and were predominantly four months or older at death. The demonstration of previous haemorrhagic foci in babies showing no other pathological abnormality may represent a histological hallmark of previous 'near-miss' episodes of hypoxaemia from whatever cause.

Female↗