Highly potent and selective heptapeptide antagonists of the neurokinin NK-2 receptor.

Incorporation of D-Pro9 into substance P related peptides is known to enhance neurokinin NK-2 receptor agonist potency and selectivity with respect to other neurokinin receptors. We now report that replacement of D-Trp9 by D-Pro9 in the nonselective neurokinin antagonist [Arg5,D-Trp7,9, Nle11]-SP(5-11) gave a partial agonist with NK-2 receptor selectivity. Further incorporation of Pro10 provided the weak but selective NK-2 antagonist Arg-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH2 (compound 4; NK-2 pKB = 5.

Diagnosing the 'strange' child.

The diagnosis of children with a spectrum of autistic features, who do not qualify for the diagnosis of classical autism, has increased during the past decade. A case is reported of an 8-year-old child originally diagnosed as learning disabled with attention disorders and hyperactivity, who was later diagnosed as having an autistic spectrum disorder when abnormalities of social interaction and play activity became more obvious. The frequency of learning and attention problems in school-age children may obscure more significant psychiatric pathologies, such as autistic disorders.

Weissenbacher-Zweymuller syndrome: long-term follow-up of growth and psychomotor development.

A child with the distinguishing characteristics of Weissenbacher-Zweymuller syndrome (WZS), a rare syndrome characterized by multiple skeletal and radiological abnormalities, dwarfism and developmental delays, was followed from birth to eight years. Follow-up showed that the radiographic anomalies eventually disappeared, and that height, motor, cognitive and language development returned to normal by eight years of age. The child's normal development at school age supports the theory that WZS is a dysmaturational, rather than dysplastic, syndrome.

Reporting of communicable diseases by university physicians.

Billing records from the outpatient clinics of the University of Arizona were compared to case reports of communicable diseases received by the local health department. Of 286 cases of reportable diseases found, 183 (64 percent) were reported to the local health department. Sexually transmitted diseases were more likely to be reported than other diseases [risk ratio (RR) = 1.

Detection of lymphomatous bone marrow involvement with magnetic resonance imaging.

We reviewed magnetic resonance (MR) staging examinations of 98 patients with malignant lymphoma who failed other therapy and were under evaluation for bone marrow transplantation. MR scan results were compared with blind posterior iliac crest aspirations and biopsies. Images of vertebral, pelvic, and femoral marrow were obtained using a standard T1-weighted, short repetition time (TR), short time to echo (TE) (TR700/TE22), spin-echo (T1-SE) method in 92 patients and short TI inversion recovery (STIR) technique (TR1,500/TE36/TI100) in all.

A community pre-registration year: the continuation of a community-oriented medical school curriculum.

A voluntary community-based preregistration year (internship) was created for graduates of a community-oriented medical school in Beersheva, Israel. Graduates were placed in community clinics which had been upgraded to meet the needs of the programme through provision of on-site laboratory facilities and specialist consultation, and placement of social workers and health education personnel in the clinics. The graduates participated in a weekly postgraduate education programme directed to their specific needs.

Imaging and treatment of B-cell lymphoma.

Ten patients with non-Hodgkin's lymphoma have been evaluated as candidates for experimental radioimmunotherapy and five of those patients have been treated with a single high dose of iodine-131-(131I) labeled anti-pan B-cell antibodies. The evaluation protocol involved collecting biodistribution data by quantitation of gamma camera images and by tumor biopsy from trace labeled doses of antibody, to estimate the relative radiation dose delivered to normal organs and tumor sites. Each patient received up to three escalating mass doses (0.

"Abandoned" parents. Loss of traditional family support systems. A challenge for health professionals.

Maternal incompetence in childrearing is described in three widely different cultural settings in the southern Negev area of Israel. It is suggested that this incompetence stems from "abandonment" of the parents by traditional family support systems and is reinforced by the inability or lack of readiness of the health system to supply the missing support mechanisms. This picture of parental "abandonment" in widely different cultural settings in Israel may represent an end result of cultural and social upheaval common to other communities in the world.

The sustained second phase of hormone-stimulated diacylglycerol accumulation does not activate protein kinase C in GH3 cells.

Numerous hormones activate cells through receptor-regulated hydrolysis of phosphoinositides resulting in elevated cellular diacylglycerol (DAG), an activator of protein kinase C (PKC). Our previous studies showed that thyrotropin-releasing hormone (TRH) treatment of GH3 cells stimulated a rapid (less than 10 s) but transient (less than 60 s) association of cytosolic PKC with the membrane. In this study, we investigated the roles of hormone-stimulated Ca2+ and DAG levels in initiating and terminating the membrane association of PKC.

High dose radiolabeled antibody therapy of lymphoma.

A trial has been initiated testing the effects of high dose radiolabeled monoclonal antibody administered in conjunction with marrow transplantation for treatment of lymphoma. This study is based on observations in mice demonstrating that radiolabeled antibody against a normal lymphocyte-associate antigen can induce regression of lymphoma masses. These preclinical studies also showed that large amounts of antibody are needed to achieve adequate biodistribution in vivo and that potentially curative doses of radionuclide induce substantial hematopoietic toxicity.

Intertrochanteric femoral fractures. Mechanical failure after internal fixation.

In a prospective study we assessed the causes of mechanical failure in a series of 230 intertrochanteric femoral fractures which had been internally fixed with either a sliding hip screw or a Küntscher Y-nail. The overall rate of mechanical failure was 16.5%; cutting-out of the implant from the femoral head was the cause in three-quarters of the instances.

Primary sequence of a motor neuron-selective adhesive site in the synaptic basal lamina protein S-laminin.

S-laminin, a novel homolog of laminin, is concentrated in a subset of basal laminae including the basal lamina that passes between motor nerve terminals and muscle fibers at the neuromuscular junction. Here we used recombinant fragments to localize a neuronal attachment site to the C-terminal 10% of s-laminin. We then used synthetic peptides spanning the active fragment to identify the primary sequence of the adhesive site as Leu-Arg-Glu (LRE): neurons attach to an immobilized LRE-containing peptide, and soluble LRE blocks attachment of neurons to the s-laminin fragment.

Acute toxicity of industrial surfactants to Mysidopsis bahia.

Three- to eight-day old Mysidopsis bahia were used to evaluate the acute toxicities of 17 industrial surfactants having a wide range of physiochemical characteristics. LC50s based on nominal concentrations covered approximately three orders of magnitude (less than 1 to greater than 4,000 mg/L). The base structure of the surfactants (i.

Dopamine withdrawal and addition of thyrotropin-releasing hormone stimulate membrane translocation of protein kinase-C and phosphorylation of an endogenous 80K substrate in enriched lactotrophs.

The biochemical mechanisms underlying the direct stimulatory action of dopamine (DA) withdrawal on PRL release and on the potentiation of TRH stimulation are not known. These actions can be mimicked by pretreatment of lactotrophs with the protein kinase-C (PKC) activator 12-O-tetradecanoyl-phorbol-13-acetate. Previous studies have shown that administration of TRH or withdrawal of DA stimulates polyphosphoinositide breakdown, although to different degrees.